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Suresh V, Shamim MA, Ghosh V, Dave T, Jayan M, Verma A, Sanker V, Roy P, Bardhan M. SGLT2 Inhibitors in COVID-19: Umbrella Review, Meta-Analysis, and Bayesian Sensitivity Assessment. Diseases 2025; 13:67. [PMID: 40136608 PMCID: PMC11941288 DOI: 10.3390/diseases13030067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/27/2025] [Accepted: 02/01/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Several studies have reported a reduced risk of COVID-19-related mortality in patients taking antidiabetic medications. This is an umbrella review, meta-analysis, and Bayesian sensitivity assessment of SGLT2 inhibitors (SGLT2is) in COVID-19 patients with type 2 diabetes mellitus (T2DM). METHODS A search was conducted on the MEDLINE (PubMed), EMBASE, Cochrane, and ClinicalTrials.gov databases on 5/12/2023. We performed an umbrella review of systematic reviews and meta-analyses on the effects of SGLT2is in T2DM patients with COVID-19 and critically appraised them using AMSTAR 2.0. Trials investigating SGLT2i use in COVID-19 patients post-hospitalisation and observational studies on prior SGLT2i use among COVID-19 patients were included in the meta-analysis, adhering to the PRISMA guidelines. RESULTS SGLT2is exhibited significantly lower odds of mortality (OR 0.67, 95% CI 0.53-0.84) and hospitalisation (OR 0.84, 0.75-0.94) in COVID-19 patients with T2DM. Bayesian sensitivity analyses corroborated most of the findings, with differences observed in hospitalisation and mortality outcomes. SGLT-2 inhibitors showed an OR of 1.20 (95% CI 0.64-2.27) for diabetic ketoacidosis. Publication bias was observed for hospitalisation, but not for mortality. The GRADE assessment indicated a low to very low quality of evidence because of the observational studies included. CONCLUSIONS The prophylactic use of SGLT2is reduces mortality and hospitalisation among COVID-19 patients, particularly in patients with diabetes. The utility of SGLT2is after hospitalisation is uncertain and warrants further investigation. A limited efficacy has been observed under critical conditions. Individualised assessment is crucial before integration into COVID-19 management.
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Affiliation(s)
- Vinay Suresh
- King George’s Medical University, Lucknow 226003, India
| | - Muhammad Aaqib Shamim
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Victor Ghosh
- Andhra Medical College, Visakhapatnam 530002, India
| | - Tirth Dave
- Bukovinian State Medical University, 58002 Chernivtsi, Ukraine
| | - Malavika Jayan
- Department of Internal Medicine, Bangalore Medical College and Research Institute, Bangalore 560002, India
| | - Amogh Verma
- Department of Internal Medicine, Rama Medical College Hospital and Research Centre, Hapur 245304, India
| | - Vivek Sanker
- Department of Neurosurgery, Trivandrum Medical College Hospital, Trivandrum 695011, India
| | - Priyanka Roy
- Department of Labour, Government of West Bengal, Kolkata 700001, India
| | - Mainak Bardhan
- The Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
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Yang Y, Zhao L, Wang Y, Liu C, Ke T. Effects of novel glucose-lowering drugs on the COVID-19 patients with diabetes: A network meta-analysis of clinical outcomes. Int J Diabetes Dev Ctries 2024; 44:426-436. [DOI: 10.1007/s13410-023-01228-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/27/2023] [Indexed: 01/03/2025] Open
Abstract
Abstract
Objective
This study aimed to assess the effects of sodium-glucose co-transporter inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) on individuals subjected to diabetes and COVID-19.
Methods
PubMed, Embase, Web of Science, and Cochrane Library were systematically searched to cover studies (except for case reports and review studies) published until August 30, 2022. The primary outcome was the mortality of people with diabetes and COVID-19. The secondary outcomes comprised the requiring intensive care unit (ICU) admission and mechanical ventilation. Two reviewers independently screened studies, abstracted data, and assessed risk-of-bias. Furthermore, the network meta-analyses (NMA) were conducted.
Results
A total of 12 trials were involved in the analysis. The OR and 95% CI of mortality for SGLT2i compared with SGLT2i + GLP-1RA and DPP4i reached 0.41 (0.17,0.97) and 0.69 (0.49,0.98), respectively. The OR and 95% CI of requiring mechanical ventilation for SGLT2i compared with the DPP4i reached 0.85 (0.75,0.97).
Conclusions
As revealed by the result of this study, SGLT2i is associated with the lower mortality rate in people with diabetes and COVID-19 among novel glucose-lowering drugs. And SGLT2i is linked to lower requiring mechanical ventilation. These findings can have a large impact on clinicians' decisions amid the COVID-19 pandemic.
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Tisch C, Xourgia E, Exadaktylos A, Ziaka M. Potential use of sodium glucose co-transporter 2 inhibitors during acute illness: a systematic review based on COVID-19. Endocrine 2024; 85:660-675. [PMID: 38448675 PMCID: PMC11291544 DOI: 10.1007/s12020-024-03758-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/19/2024] [Indexed: 03/08/2024]
Abstract
OBJECTIVE SGLT-2i are increasingly recognized for their benefits in patients with cardiometabolic risk factors. Additionally, emerging evidence suggests potential applications in acute illnesses, including COVID-19. This systematic review aims to evaluate the effects of SGLT-2i in patients facing acute illness, particularly focusing on SARS-CoV-2 infection. METHODS Following PRISMA guidelines, a systematic search of PubMed, Scopus, medRxiv, Research Square, and Google Scholar identified 22 studies meeting inclusion criteria, including randomized controlled trials and observational studies. Data extraction and quality assessment were conducted independently. RESULTS Out of the 22 studies included in the review, six reported reduced mortality in DM-2 patients taking SGLT-2i, while two found a decreased risk of hospitalization. Moreover, one study demonstrated a lower in-hospital mortality rate in DM-2 patients under combined therapy of metformin plus SGLT-2i. However, three studies showed a neutral effect on the risk of hospitalization. No increased risk of developing COVID-19 was associated with SGLT-2i use in DM-2 patients. Prior use of SGLT-2i was not associated with ICU admission and need for MV. The risk of acute kidney injury showed variability, with inconsistent evidence regarding diabetic ketoacidosis. CONCLUSION Our systematic review reveals mixed findings on the efficacy of SGLT-2i use in COVID-19 patients with cardiometabolic risk factors. While some studies suggest potential benefits in reducing mortality and hospitalizations, others report inconclusive results. Further research is needed to clarify optimal usage and mitigate associated risks, emphasizing caution in clinical interpretation.
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Affiliation(s)
- Carmen Tisch
- Department of Internal Medicine, Thun General Hospital, Thun, Switzerland
| | - Eleni Xourgia
- Department of Cardiology, Inselspital, University Hospital, University of Bern, 3008, Bern, Switzerland
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
| | - Aristomenis Exadaktylos
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
| | - Mairi Ziaka
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
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Wang M, Li M, Wang L, Wang F, Cao X, Li S, Zheng Z. Association of Sodium-Glucose Cotransporter-2 Inhibitors vs Dipeptidyl Peptidase-4 Inhibitors With Pneumonia, COVID-19, and Other Adverse Respiratory Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis. Can J Diabetes 2024; 48:364-372.e1. [PMID: 38636589 DOI: 10.1016/j.jcjd.2024.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 04/02/2024] [Accepted: 04/06/2024] [Indexed: 04/20/2024]
Abstract
OBJECTIVE Our aim in this study was to systematically assess the association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM). METHODS PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2i (exposure group) or DPP4i (control group). Stata version 15.0 statistical software was used for the meta-analysis. RESULTS Ten studies were included, all 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2i had a lower incidence of pneumonia (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.51 to 0.74) and pneumonia risk (OR 0.63, 95% CI 0.60 to 0.68, p=0.000) compared with those receiving DPP4i. The same situation was seen for mortality for pneumonia (OR 0.49, 95% CI 0.39 to 0.60) and pneumonia mortality risk (OR 0.47, 95% CI 0.42 to 0.51). There was lower mortality due to COVID-19 (OR 0.31, 95% CI 0.28 to 0.34) and a lower hospitalization rate (OR 0.61, 95% CI 0.56 to 0.68, p=0.000) and incidence of mechanical ventilation (OR 0.69, 95% CI 0.58 to 0.83, p=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2i. Qualitative analysis results show that SGLT2i were associated with a lower incidence of COVID-19, lower risk of obstructive airway disease events, and lower hospitalization rate of health-care-associated pneumonia than DPP4i. CONCLUSION In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i.
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Affiliation(s)
- Mengna Wang
- Guizhou Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guiyang, Guizhou, China; Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Ming Li
- Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Libin Wang
- Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
| | - Fang Wang
- Guizhou Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guiyang, Guizhou, China
| | - Xulin Cao
- Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Shengyou Li
- Guizhou Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guiyang, Guizhou, China
| | - Zhichang Zheng
- Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
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Song ZH, Huang QM, Xu SS, Zhou JB, Zhang C. The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies. Ther Innov Regul Sci 2024; 58:773-787. [PMID: 38683419 DOI: 10.1007/s43441-024-00633-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 02/09/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19. METHODS We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications. RESULTS 56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography. CONCLUSION Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.
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Affiliation(s)
- Zhi-Hui Song
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Qiao-Ming Huang
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Shan-Shan Xu
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jian-Bo Zhou
- Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
| | - Chao Zhang
- Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
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Dimnjaković J, Buble T, Ivanko P, Pristaš I, Brborović O, Brborović H. Association of anti-diabetic drugs and COVID-19 outcomes in patients with diabetes mellitus type 2 and cardiomyopathy. Sci Rep 2024; 14:7227. [PMID: 38538694 PMCID: PMC10973387 DOI: 10.1038/s41598-024-57871-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 03/22/2024] [Indexed: 01/03/2025] Open
Abstract
There is a scarcity of information on the population with diabetes mellitus type 2 and cardiomyopathy (PDMC) in COVID-19, especially on the association between anti-diabetic medications and COVID-19 outcomes. Study is designed as a retrospective cohort analysis covering 2020 and 2021. Data from National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed. Of 231 796 patients with diabetes mellitus type 2 in the database, 14 485 patients had cardiomyopathy. The two2-year cumulative incidence of all three studies' COVID-19 outcomes was higher in PDMC than in the general diabetes population (positivity 15.3% vs. 14.6%, p = 0.01; hospitalization 7.8% vs. 4.4%, p < 0.001; death 2.6% vs. 1.2%, p < 0.001). Sodium-Glucose Transporter 2 (SGLT-2) inhibitors therapy was found to be protective of SARS-CoV-2 infections [OR 0.722 (95% CI 0.610-0.856)] and COVID-19 hospitalizations [OR 0.555 (95% CI 0.418-0.737)], sulfonylureas to be risk factors for hospitalization [OR 1.184 (95% CI 1.029-1.362)] and insulin to be a risk factor for hospitalization [OR 1.261 (95% CI 1.046-1.520)] and death [OR 1.431 (95% CI 1.080-1.897)]. PDMC are at greater risk of acquiring SARS-CoV-2 infection and having worse outcomes than the general diabetic population. SGLT-2 inhibitors therapy was a protective factor against SARS-CoV-2 infection and against COVID-19 hospitalization, sulfonylurea was the COVID-19 hospitalization risk factor, while insulin was a risk factor for all outcomes. Further research is needed in this diabetes sub-population.
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Affiliation(s)
- Jelena Dimnjaković
- Division for Health Informatics and Biostatistics, Croatian Institute of Public Health, Rockefeller's Street 7, 10 000, Zagreb, Croatia
| | - Tamara Buble
- Division for Health Informatics and Biostatistics, Croatian Institute of Public Health, Rockefeller's Street 7, 10 000, Zagreb, Croatia
| | - Pero Ivanko
- Division for Health Informatics and Biostatistics, Croatian Institute of Public Health, Rockefeller's Street 7, 10 000, Zagreb, Croatia
| | - Ivan Pristaš
- Division for Health Informatics and Biostatistics, Croatian Institute of Public Health, Rockefeller's Street 7, 10 000, Zagreb, Croatia
| | - Ognjen Brborović
- School of Medicine, Andrija Štampar School of Public Health, Department of Social Medicine and Health Care Organization, University of Zagreb, Rockefeller's Street 4, 10 000, Zagreb, Croatia.
| | - Hana Brborović
- School of Medicine, Andrija Štampar School of Public Health, Department of Environmental and Occupational Health and Sports Medicine, University of Zagreb, Rockefeller's Street 4, 10 000, Zagreb, Croatia
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Gonikman D, Kustovs D. Antidiabetic Drug Efficacy in Reduction of Mortality during the COVID-19 Pandemic. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1810. [PMID: 37893528 PMCID: PMC10608676 DOI: 10.3390/medicina59101810] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023]
Abstract
Background and Objectives: The COVID-19 pandemic caused by the Coronavirus SARS-CoV-2 is a complex challenge for the existing scientific and medical landscape. It is an ongoing public health crisis, with over 245,373,039 confirmed cases globally, including 4,979,421 deaths as of 29 October 2021. Exploring molecular mechanisms correlated with the disease's severity has demonstrated significant factors of immune compromise, noted in diabetic patients with SARS-CoV-2 infections. Among diabetics, the altered function of the immune system allows for better penetration of the virus into epithelial cells, increased viral binding affinity due to hyperglycemia, reduced T cell function, decreased viral clearance, high risks of cytokine storm, and hyper-inflammatory responses, altogether increasing the susceptibility of these patients to an extreme COVID-19 disease course. Materials and Methods: This research involved a systematic literature search among various databases comprising PubMed and Google Scholar in determining credible studies about the effects of antidiabetic drugs on the high mortality rates among diabetic patients infected with COVID-19. The primary search found 103 results. Duplicated results, non-pertinent articles, and the unavailability of full text were excluded. Finally, we included 74 articles in our review. The inclusion criteria included articles published during 2020-2023, studies that reported a low risk of bias, and articles published in English. Exclusion criteria included studies published in non-peer-reviewed sources, such as conference abstracts, thesis papers, or non-academic publications. Results: Among the studied anti-diabetic drugs, Metformin, the Glucagon-like peptide 1 receptor agonist (GLP-1RA), and Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have demonstrated decreased mortality rates among diabetic patients infected with COVID-19. Insulin and Dipeptidyl peptidase 4 inhibitors (DPP-4i) have demonstrated increased mortality rates, while Sulfonylureas, Thiazolidinedione (TZD), and Alpha-glucosidase inhibitors (AGI) have demonstrated mortality-neutral results.
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Affiliation(s)
- Daniel Gonikman
- Student of Faculty of Medicine, Riga Stradins University, LV-1007 Riga, Latvia
| | - Dmitrijs Kustovs
- Department of Pharmacology, Riga Stradins University, LV-1007 Riga, Latvia;
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Zhang J, Ma X, Liu F, Zhang D, Ling J, Zhu Z, Chen Y, Yang P, Yang Y, Liu X, Zhang J, Liu J, Yu P. Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention. Front Immunol 2023; 14:1203389. [PMID: 37868953 PMCID: PMC10585100 DOI: 10.3389/fimmu.2023.1203389] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.
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Affiliation(s)
- Jiayu Zhang
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Huankui Academy, Nanchang University, Jiangxi, Nanchang, China
| | - Xuejing Ma
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Fuwei Liu
- Department of Cardiology, The Affiliated Ganzhou Hospital of Nanchang University, Jiangxi, China
| | - Deju Zhang
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jitao Ling
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zicheng Zhu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yixuan Chen
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Pingping Yang
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yanlin Yang
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiao Liu
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jianping Liu
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Peng Yu
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Salgado-Barreira A, Seijas-Amigo J, Rodriguez-Mañero M, Piñeiro-Lamas M, Eiras S, Cordero A, Gonzalez-Juanatey JR, Figueiras A. Effect of dapagliflozin on COVID-19 infection and risk of hospitalization. J Antimicrob Chemother 2023; 78:2335-2342. [PMID: 37549309 PMCID: PMC10477113 DOI: 10.1093/jac/dkad241] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 07/19/2023] [Indexed: 08/09/2023] Open
Abstract
BACKGROUND Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection. METHODS We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model. RESULTS We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015). CONCLUSIONS Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.
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Affiliation(s)
- Angel Salgado-Barreira
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Carlos III Health Institute, Madrid, Spain
| | - Jose Seijas-Amigo
- Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - Moises Rodriguez-Mañero
- Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - María Piñeiro-Lamas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Carlos III Health Institute, Madrid, Spain
| | - Sonia Eiras
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
- Translational Cardiology Group, Institute of Biomedical Research of Santiago de Compostela (IDIS-SERGAS), Santiago de Compostela, Spain
| | - Alberto Cordero
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
- Cardiology Department, Hospital Universitario de San Juan, Alicante, Spain
- Unidad de Investigación en Cardiología, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
| | - Jose Ramon Gonzalez-Juanatey
- Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - Adolfo Figueiras
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Carlos III Health Institute, Madrid, Spain
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10
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Kow CS, Ramachandram DS, Hasan SS. The impact of preadmission/prediagnosis use of GLP-1 receptor agonists on COVID-19 mortality in patients with diabetes: A systematic review and meta-analysis. Health Sci Rep 2023; 6:e1549. [PMID: 37720167 PMCID: PMC10500111 DOI: 10.1002/hsr2.1549] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/17/2023] [Accepted: 08/25/2023] [Indexed: 09/19/2023] Open
Affiliation(s)
- Chia Siang Kow
- Department of Pharmacy PracticeSchool of Pharmacy, International Medical UniversityKuala LumpurMalaysia
| | | | - Syed Shahzad Hasan
- Department of PharmacySchool of Applied Sciences, University of HuddersfieldHuddersfieldUK
- School of Biomedical Sciences & PharmacyUniversity of NewcastleCallaghanAustralia
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11
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Greco S, Monda VM, Valpiani G, Napoli N, Crespini C, Pieraccini F, Marra A, Passaro A. The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study. Biomedicines 2023; 11:2292. [PMID: 37626788 PMCID: PMC10452157 DOI: 10.3390/biomedicines11082292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/11/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Novel antidiabetic drugs have the ability to produce anti-inflammatory effects regardless of their glucose-lowering action. For this reason, these molecules (including GLP-1 RAs and DPP-4is) were hypothesized to be effective against COVID-19, which is characterized by cytokines hyperactivity and multiorgan inflammation. The aim of our work is to explore the potential protective role of GLP-1 RAs and DPP-4is in COVID-19 (with the disease intended to be a model of an acute stressor) and non-COVID-19 patients over a two-year observation period. Retrospective and one-versus-one analyses were conducted to assess the impact of antidiabetic drugs on the need for hospitalization (in both COVID-19- and non-COVID-19-related cases), in-hospital mortality, and two-year mortality. Logistic regression analyses were conducted to identify the variables associated with these outcomes. Additionally, log-rank tests were used to plot survival curves for each group of subjects, based on their antidiabetic treatment. The performed analyses revealed that despite similar hospitalization rates, subjects undergoing home therapy with GLP-1 RAs exhibited significantly lower mortality rates, even over a two-year period. These individuals demonstrated improved survival estimates both within hospital and non-hospital settings, even during a longer observation period.
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Affiliation(s)
- Salvatore Greco
- Department of Translational Medicine, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, FE, Italy;
- Department of Internal Medicine, Ospedale del Delta, Via Valle Oppio, 2, I-44023 Lagosanto, FE, Italy
| | - Vincenzo M. Monda
- Primary Care Department, Diabetes Unit of “SS. Annunziata” Hospital, Via Giovanni Vicini 2, I-44042 Cento, FE, Italy;
| | - Giorgia Valpiani
- Research and Innovation Section, University Hospital of Ferrara Arcispedale Sant’Anna, Via Aldo Moro 8, I-44124 Cona, FE, Italy;
| | - Nicola Napoli
- Programming and Management Control Unit, University Hospital of Ferrara Arcispedale Sant’Anna, Via Aldo Moro 8, I-44124 Cona, FE, Italy;
| | - Carlo Crespini
- Pharmaceutical Department, University Hospital of Ferrara Arcispedale Sant’Anna, Via Aldo Moro 8, I-44124 Cona, FE, Italy; (C.C.); (A.M.)
| | - Fabio Pieraccini
- Pharmaceutical Care Department, Azienda Unità Sanitaria Locale della Romagna, Via Carlo Forlanini 34, I-47121 Forlì, FC, Italy;
| | - Anna Marra
- Pharmaceutical Department, University Hospital of Ferrara Arcispedale Sant’Anna, Via Aldo Moro 8, I-44124 Cona, FE, Italy; (C.C.); (A.M.)
| | - Angelina Passaro
- Department of Translational Medicine, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, FE, Italy;
- Research and Innovation Section, University Hospital of Ferrara Arcispedale Sant’Anna, Via Aldo Moro 8, I-44124 Cona, FE, Italy;
- Department of Internal Medicine, University Hospital of Ferrara Arcispedale Sant’Anna, Via Aldo Moro 8, I-44124 Cona, FE, Italy
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12
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Siebert HC, Eckert T, Bhunia A, Klatte N, Mohri M, Siebert S, Kozarova A, Hudson JW, Zhang R, Zhang N, Li L, Gousias K, Kanakis D, Yan M, Jiménez-Barbero J, Kožár T, Nifantiev NE, Vollmer C, Brandenburger T, Kindgen-Milles D, Haak T, Petridis AK. Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms. Biomedicines 2023; 11:biomedicines11051421. [PMID: 37239092 DOI: 10.3390/biomedicines11051421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/02/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.
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Affiliation(s)
- Hans-Christian Siebert
- RI-B-NT-Research Institute of Bioinformatics and Nanotechnology, Schauenburgerstr. 116, 24118 Kiel, Germany
| | - Thomas Eckert
- Department of Chemistry and Biology, University of Applied Sciences Fresenius, Limburger Str. 2, 65510 Idstein, Germany
- RISCC-Research Institute for Scientific Computing and Consulting, Ludwig-Schunk-Str. 15, 35452 Heuchelheim, Germany
- Institut für Veterinärphysiologie und Biochemie, Fachbereich Veterinärmedizin, Justus-Liebig Universität Gießen, Frankfurter Str. 100, 35392 Gießen, Germany
| | - Anirban Bhunia
- Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700054, India
| | - Nele Klatte
- Department of Chemistry and Biology, University of Applied Sciences Fresenius, Limburger Str. 2, 65510 Idstein, Germany
| | - Marzieh Mohri
- RI-B-NT-Research Institute of Bioinformatics and Nanotechnology, Schauenburgerstr. 116, 24118 Kiel, Germany
| | - Simone Siebert
- RI-B-NT-Research Institute of Bioinformatics and Nanotechnology, Schauenburgerstr. 116, 24118 Kiel, Germany
| | - Anna Kozarova
- Department of Biomedical Sciences, University of Windsor, Windsor, ON N9B 3P4, Canada
| | - John W Hudson
- Department of Biomedical Sciences, University of Windsor, Windsor, ON N9B 3P4, Canada
| | - Ruiyan Zhang
- Institute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, China
| | - Ning Zhang
- Institute of BioPharmaceutical Research, Liaocheng University, Liaocheng 252059, China
| | - Lan Li
- Klinik für Neurochirurgie, Alfried Krupp Krankenhaus, Rüttenscheid, Alfried-Krupp-Straße 21, 45131 Essen, Germany
| | - Konstantinos Gousias
- Klinik für Neurochirurgie, Klinikum Lünen, St.-Marien-Hospital, Akad. Lehrkrankenhaus der Westfälische Wilhelms-Universität Münster, 44534 Lünen, Germany
| | - Dimitrios Kanakis
- Institute of Pathology, University of Nicosia Medical School, 2408 Egkomi, Cyprus
| | - Mingdi Yan
- Department of Chemistry, University of Massachusetts Lowell, 1 University Avenue, Lowell, MA 01854, USA
| | | | - Tibor Kožár
- Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Šafárik University, Jesenná 5, 04001 Košice, Slovakia
| | - Nikolay E Nifantiev
- Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia
| | - Christian Vollmer
- Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
| | - Timo Brandenburger
- Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
| | - Detlef Kindgen-Milles
- Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine University Duesseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany
| | - Thomas Haak
- Diabetes Klinik Bad Mergentheim, Theodor-Klotzbücher-Str. 12, 97980 Bad Mergentheim, Germany
| | - Athanasios K Petridis
- Medical School, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany
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13
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Nassar M, Abosheaishaa H, Singh AK, Misra A, Bloomgarden Z. Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis. J Diabetes 2023; 15:86-96. [PMID: 36690377 PMCID: PMC9934962 DOI: 10.1111/1753-0407.13359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/12/2022] [Accepted: 01/05/2023] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19. METHODS We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. RESULTS The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04). CONCLUSIONS AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.
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Affiliation(s)
- Mahmoud Nassar
- Department of MedicineIcahn School of Medicine at Mount Sinai/NYC Health+Hospitals/QueensNew York CityNew YorkUSA
| | - Hazem Abosheaishaa
- Department of MedicineIcahn School of Medicine at Mount Sinai/NYC Health+Hospitals/QueensNew York CityNew YorkUSA
| | - Awadhesh Kumar Singh
- Department of Diabetes & EndocrinologyGD Hospital & Diabetes InstituteKolkataIndia
| | - Anoop Misra
- Chairman, Fortis‐C‐DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Diabetes Foundation (India), and National Diabetes Obesity and Cholesterol Foundation (NDOC)New DelhiIndia
| | - Zachary Bloomgarden
- Department of Medicine, Division of Endocrinology, Diabetes and Bone DiseaseIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
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14
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Permana H, Audi Yanto T, Ivan Hariyanto T. Pre-admission use of sodium glucose transporter-2 inhibitor (SGLT-2i) may significantly improves Covid-19 outcomes in patients with diabetes: A systematic review, meta-analysis, and meta-regression. Diabetes Res Clin Pract 2023; 195:110205. [PMID: 36502891 PMCID: PMC9731816 DOI: 10.1016/j.diabres.2022.110205] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 12/14/2022]
Abstract
AIMS This study aims to examine the effectiveness of using sodium glucose transporter-2 inhibitor (SGLT-2i) before hospital admission on Covid-19 outcomes in diabetic patients. METHODS A literature search was conducted using specific keywords until October 24th, 2022 on 4 databases: Medline, Scopus, Cochrane Library, and ClinicalTrials.gov. All articles regarding SGLT-2i in diabetic patients with Covid-19 were included in the study. Outcomes in this study were calculated using random-effect models to generate pooled odds ratio (OR) with 95% confidence intervals (CI). RESULTS A total of 17 studies were included in the analysis. Our meta-analysis showed that pre-admission use of SGLT-2i was associated with reduced mortality (OR 0.69; 95 %CI: 0.56 - 0.87, p = 0.001, I2 = 91 %) and severity of Covid-19 (OR 0.88; 95 %CI: 0.80 - 0.97, p = 0.008, I2 = 13 %). This benefit of SGLT-2i on Covid-19 mortality was not significantly affected by patient's factors such as age (p = 0.2335), sex (p = 0.2742), hypertension (p = 0.2165), heart failure (p = 0.1616), HbA1c levels (p = 0.4924), metformin use (p = 0.6617), duration of diabetes (p = 0.7233), and BMI (p = 0.1797). CONCLUSIONS This study suggests that SGLT-2i as glucose lowering treatment in patients with diabetes has a positive effect on Covid-19 outcomes, therefore can be considered as an antidiabetic drug of choice, especially during the Covid-19 pandemic. Short Title: SGLT-2i in diabetes and Covid-19. REGISTRATION DETAILS CRD42022369784.
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Affiliation(s)
- Hikmat Permana
- Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Padjadjaran University, Bandung, West Java 45363, Indonesia
| | - Theo Audi Yanto
- Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang 15811, Indonesia
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15
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Zhang L, Jiang F, Xie Y, Mo Y, Zhang X, Liu C. Diabetic endothelial microangiopathy and pulmonary dysfunction. Front Endocrinol (Lausanne) 2023; 14:1073878. [PMID: 37025413 PMCID: PMC10071002 DOI: 10.3389/fendo.2023.1073878] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 02/17/2023] [Indexed: 04/08/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with a high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by the macrovascular and microvascular bed degradation brought on by metabolic, hemodynamic, and inflammatory variables. However, research in recent years has expanded the target organ in T2DM to include the lung. Inflammatory lung diseases also impose a severe financial burden on global healthcare. T2DM has long been recognized as a significant comorbidity that influences the course of various respiratory disorders and their disease progress. The pathogenesis of the glycemic metabolic problem and endothelial microangiopathy of the respiratory disorders have garnered more attention lately, indicating that the two ailments have a shared history. This review aims to outline the connection between T2DM related endothelial cell dysfunction and concomitant respiratory diseases, including Coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
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Affiliation(s)
- Lanlan Zhang
- Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Lanlan Zhang, ; Xin Zhang, ; Chuntao Liu,
| | - Faming Jiang
- Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Yingying Xie
- Department of Nephrology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yan Mo
- Department of Neurology Medicine, The Aviation Industry Corporation of China (AVIC) 363 Hospital, Chengdu, China
| | - Xin Zhang
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Lanlan Zhang, ; Xin Zhang, ; Chuntao Liu,
| | - Chuntao Liu
- Department of Respiratory and Critical Care Medicine, Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Lanlan Zhang, ; Xin Zhang, ; Chuntao Liu,
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16
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Zhu Z, Zeng Q, Liu Q, Wen J, Chen G. Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19: A Systematic Review and Network Meta-analysis. JAMA Netw Open 2022; 5:e2244652. [PMID: 36472874 PMCID: PMC9856231 DOI: 10.1001/jamanetworkopen.2022.44652] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
IMPORTANCE Patients with COVID-19 have a high prevalence of diabetes, and diabetes and blood glucose control are determinants of intensive care unit admission and mortality. OBJECTIVE To evaluate the association between COVID-19-related adverse outcomes and 8 antihyperglycemic drugs in patients with diabetes who were subsequently diagnosed and hospitalized with COVID-19. DATA SOURCES Data were retrieved and collected in PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov from database inception to September 5, 2022. STUDY SELECTION For this systematic review and network meta-analysis, randomized clinical trials and observational studies conducted among patients with diabetes while receiving glucose-lowering therapies for at least 14 days before the confirmation of COVID-19 infection were included after blinded review by 2 independent reviewers and consultations of disagreement by a third independent reviewer. Of 1802 studies initially identified, 31 observational studies met the criteria for further analysis. DATA EXTRACTION AND SYNTHESIS This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Bayesian network meta-analyses were performed with random effects. MAIN OUTCOMES AND MEASURES A composite adverse outcome, including the need for intensive care unit admission, invasive and noninvasive mechanical ventilation, or in-hospital death. RESULTS Thirty-one distinct observational studies (3 689 010 patients with diabetes hospitalized for COVID-19) were included. The sodium-glucose cotransporter-2 inhibitors (SGLT-2is) were associated with relatively lower risks of adverse outcomes compared with insulin (log of odds ratio [logOR], 0.91; 95% credible interval [CrI], 0.57-1.26), dipeptidyl peptidase-4 inhibitors (logOR, 0.61; 95% CrI, 0.28-0.93), secretagogues (logOR, 0.37; 95% CrI, 0.02-0.72), and glucosidase inhibitors (logOR, 0.50; 95% CrI, 0.00-1.01). Based on the surface under the cumulative ranking curves value, SGLT-2is were associated with the lowest probability for adverse outcomes (6%), followed by glucagon-like peptide-1 receptor agonists (25%) and metformin (28%). A sensitivity analysis revealed that the study was reliable. CONCLUSIONS AND RELEVANCE These findings suggest that the use of an SGLT-2i before COVID-19 infection is associated with lower COVID-19-related adverse outcomes. In addition to SGLT-2is, glucagon-like peptide-1 receptor agonists and metformin were also associated with relatively low risk of adverse outcomes.
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Affiliation(s)
- Zheng Zhu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujia, China
| | - Qingya Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujia, China
| | - Qinyu Liu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujia, China
| | - Junping Wen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujia, China
- Department of Endocrinology, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Gang Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujia, China
- Department of Endocrinology, Fujian Provincial Hospital, Fuzhou, Fujian, China
- Fujian Provincial Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China
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17
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Narayanan N, Naik D, Sahoo J, Kamalanathan S. Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control. World J Virol 2022; 11:399-410. [PMID: 36483108 PMCID: PMC9724202 DOI: 10.5501/wjv.v11.i6.399] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/30/2022] [Accepted: 10/04/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.
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Affiliation(s)
- Niya Narayanan
- Department of Endocrinology, Baby Memorial Hospital, Kozhikode 673005, Kerala, India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
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18
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Khunti K, Aroda VR, Bhatt DL, Bozkurt B, Buse JB, Heerspink HL, Inzucchi SE, Lam CSP, Marx N, McMurray JJV, Solomon SD, Kosiborod MN. Re-examining the widespread policy of stopping sodium-glucose cotransporter-2 inhibitors during acute illness: A perspective based on the updated evidence. Diabetes Obes Metab 2022; 24:2071-2080. [PMID: 35801339 DOI: 10.1111/dom.14805] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/23/2022] [Accepted: 07/01/2022] [Indexed: 11/28/2022]
Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or chronic kidney disease, the risk of DKA is similar to placebo. Over the course of the COVID-19 pandemic, cases of DKA have also been reported in cases of COVID-19 hospitalizations. Consensus guidelines have recommended that SGLT2 inhibitors should be avoided in cases of serious illness and suggest they are not recommended for routine in-hospital use. However, recent data suggest potential beneficial effects of SGLT2 inhibitors in the setting of acute illness with COVID-19 with no increase in adverse events and low rates of DKA, which were non-severe. Given the low rates of DKA in cardiovascular outcome trials and in hospitalized patients with type 2 diabetes, the potential for SGLT2 inhibitors not being re-initiated following discharge and their cardiovascular and kidney benefits, we believe the practice of routine 'sick day' guidance should be re-examined based on current evidence with a call for further research in this area. Furthermore, high-quality trials of initiation of SGLT2 inhibitors in people admitted to hospital with cardiovascular disease or kidney disease, and trials of continuation of SGLT2 inhibitors in people, with careful monitoring of DKA should be conducted. These should be further supplemented with large observational studies.
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Affiliation(s)
- Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Vanita R Aroda
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Deepak L Bhatt
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Biykem Bozkurt
- Section of Cardiology, Baylor College of Medicine, Houston Baylor, Houston, Texas, USA
| | - John B Buse
- Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | | | - Silvio E Inzucchi
- Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Carolyn S P Lam
- National Heart Centre Singapore and Duke-National University of Singapore, Singapore, Singapore
| | - Nikolaus Marx
- Department of Internal Medicine I-Cardiology, RWTH Aachen University, Aachen, Germany
| | - John J V McMurray
- Department of Medicine, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Scott D Solomon
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Mikhail N Kosiborod
- Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA
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19
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Salmen T, Pietroșel VA, Mihai BM, Bica IC, Teodorescu C, Păunescu H, Coman OA, Mihai DA, Pantea Stoian A. Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19. Biomedicines 2022; 10:biomedicines10102624. [PMID: 36289885 PMCID: PMC9599217 DOI: 10.3390/biomedicines10102624] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/09/2022] [Accepted: 10/11/2022] [Indexed: 12/03/2022] Open
Abstract
The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.
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Affiliation(s)
- Teodor Salmen
- Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Valeria-Anca Pietroșel
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr N.C.Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
| | - Bianca-Margareta Mihai
- Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana Cristina Bica
- Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Claudiu Teodorescu
- Doctoral School, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Horia Păunescu
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Oana Andreia Coman
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Correspondence: (O.A.C.); (D.-A.M.); Tel.: +40-755507110 (O.A.C.); +40-723591283 (D.-A.M.)
| | - Doina-Andrada Mihai
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr N.C.Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bld. Eroii Sanitari No. 8, 050471 Bucharest, Romania
- Correspondence: (O.A.C.); (D.-A.M.); Tel.: +40-755507110 (O.A.C.); +40-723591283 (D.-A.M.)
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, “Prof. Dr N.C.Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 030167 Bucharest, Romania
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bld. Eroii Sanitari No. 8, 050471 Bucharest, Romania
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20
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Khunti K, Ruan Y, Davies J, Field BCT, Harris S, Kosiborod M, Nagi D, Narendran P, Patel D, Ryder REJ, Várnai KA, Wild SH, Wilmot EG, Rea R. Association Between SGLT2 Inhibitor Treatment and Diabetic Ketoacidosis and Mortality in People With Type 2 Diabetes Admitted to Hospital With COVID-19. Diabetes Care 2022; 45:dc220357. [PMID: 36074663 DOI: 10.2337/dc22-0357] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 08/07/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine the association between prescription of SGLT2 inhibitors (SGLT2is) and diabetic ketoacidosis (DKA) incidence or mortality in people with type 2 diabetes (T2D) hospitalized with COVID-19. RESEARCH DESIGN AND METHODS This was a retrospective cohort study based on secondary analysis of data from a large nationwide audit from a network of 40 centers in the U.K. with data collection up to December 2020. The study was originally designed to describe risk factors associated with adverse outcomes among people with diabetes who were admitted to hospital with COVID-19. The primary outcome for this analysis was DKA on or during hospital admission. The secondary outcome was mortality. Crude, age-sex adjusted, and multivariable logistic regression models were used to generate odds ratios (ORs) and 95% CIs for people prescribed SGLT2i compared with those not prescribed SGLT2i. RESULTS The original national audit included 3,067 people with T2D who were admitted to hospital with COVID-19, of whom 230 (7.5%) were prescribed SGLT2is prior to hospital admission. The mean age of the overall cohort was 72 years, 62.3% were men, and 34.9% were prescribed insulin. Overall, 2.8% of the total population had DKA and 35.6% of people in the study died. The adjusted odds of DKA were not significantly different between those prescribed SGLT2is and those not (OR 0.56; 95% CI 0.16-1.97). The adjusted odds of mortality associated with SGLT2is were similar in the total study population (OR 1.13; 95% CI 0.78-1.63), in the subgroup prescribed insulin (OR 1.02; 95% CI 0.59-1.77), and in the subgroup that developed DKA (OR 0.21; 95% CI 0.01-8.76). CONCLUSIONS We demonstrate a low risk of DKA and high mortality rate in people with T2D admitted to hospital with COVID-19 and limited power, but no evidence, of increased risk of DKA or in-hospital mortality associated with prescription of SGLT2is.
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Affiliation(s)
- Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, U.K
| | - Yue Ruan
- Oxford National Institute for Health Research Biomedical Research Centre, Oxford, U.K
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals National Health Service Foundation Trust, Oxford, U.K
| | - Jim Davies
- Oxford National Institute for Health Research Biomedical Research Centre, Oxford, U.K
- Department of Computer Science, University of Oxford, Oxford, U.K
| | - Benjamin C T Field
- Department of Clinical & Experimental Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, U.K
- Department of Diabetes & Endocrinology, Surrey & Sussex Healthcare NHS Trust, Redhill, Surrey, U.K
| | - Sophie Harris
- Department of Diabetes, King's College Hospital, London, U.K
| | - Mikhail Kosiborod
- Saint Luke's Mid America Heart Institute, Kansas City, MO
- University of Missouri, Kansas City, MO
| | - Dinesh Nagi
- Mid Yorkshire Hospitals NHS Trust, Pinderfields Hospital, Wakefield, U.K
| | - Parth Narendran
- Medical and Dental Sciences, University of Birmingham, Birmingham, U.K
- University Hospital Birmingham, NHS Foundation Trust, Birmingham, U.K
| | - Dipesh Patel
- Department of Diabetes, Division of Medicine, University College London, Royal Free Campus, London, U.K
| | - Robert E J Ryder
- Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, U.K
| | - Kinga A Várnai
- Oxford National Institute for Health Research Biomedical Research Centre, Oxford, U.K
- Oxford University Hospitals National Health Service Foundation Trust, Oxford, U.K
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, U.K
| | - Emma G Wilmot
- Department of Diabetes & Endocrinology, University Hospitals of Derby & Burton NHS Trust, Derby, U.K
- Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Nottingham, U.K
| | - Rustam Rea
- Oxford National Institute for Health Research Biomedical Research Centre, Oxford, U.K
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals National Health Service Foundation Trust, Oxford, U.K
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21
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Ferrannini G, Lund LH, Benson L, Rizzo M, Almahmeed W, Rosano GMC, Savarese G, Cosentino F. Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: a nationwide registry analysis. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2022; 9:10-17. [PMID: 35963647 PMCID: PMC9384777 DOI: 10.1093/ehjcvp/pvac044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/01/2022] [Accepted: 08/09/2022] [Indexed: 02/03/2023]
Abstract
AIMS Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. METHODS AND RESULTS Patients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. 'Incident severe COVID-19' was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA, and DPP-4i to analyse the associations between their use and (I) incident severe COVID-19 and (II) risk of 30-day mortality in patients hospitalized for COVID-19.Among 344 413 patients, 39 172 (11%) were treated with SGLT2i, 34 290 (10%) with GLP-1 RA, and 53 044 (15%) with DPP-4i; 9538 (2.8%) had incident severe COVID-19 by 15 May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i was also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. CONCLUSION SGLT2i and DPP-4i use were associated with a higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA.
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Affiliation(s)
- Giulia Ferrannini
- Division of Cardiology, Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Lars H Lund
- Division of Cardiology, Department of Medicine, Karolinska Institute, Stockholm, Sweden,Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden
| | - Lina Benson
- Division of Cardiology, Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Manfredi Rizzo
- School of Medicine, ProMISE Department, University of Palermo, Palermo, Italy
| | - Wael Almahmeed
- Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
| | - Giuseppe M C Rosano
- Centre for Clinical and Basic Research, IRCCS San Raffaele Roma, Rome, Italy
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22
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Nguyen NN, Ho DS, Nguyen HS, Ho DKN, Li HY, Lin CY, Chiu HY, Chen YC. Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis. Metabolism 2022; 131:155196. [PMID: 35367460 PMCID: PMC8970613 DOI: 10.1016/j.metabol.2022.155196] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 03/10/2022] [Accepted: 03/28/2022] [Indexed: 12/16/2022]
Abstract
BACKGROUND Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes. METHODS A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses. MAIN FINDINGS We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), I2 86%], glucagon-like peptide-1 receptor agonist (GLP-1RA) [0.51 (0.37-0.69), I2 85%], and sodium-glucose transporter-2 inhibitor (SGLT-2i) [0.60 (0.40-0.88), I2 91%]. Dipeptidyl peptidase-4 inhibitor (DPP-4i) [1.23 (1.07-1.42), I2 82%] and insulin [1.70 (1.33-2.19), I2 97%] users were more likely to die during hospitalization. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitor were mortality neutral [0.92 (95% CI 0.83-1.01, I2 44%), 0.90 (95% CI 0.71-1.14, I2 46%), and 0.61 (95% CI 0.26-1.45, I2 77%), respectively]. The sensitivity analysis indicated that our findings were robust. CONCLUSIONS Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.
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Affiliation(s)
- Nam Nhat Nguyen
- College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Dung Si Ho
- Department of Geriatric Medicine, Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Viet Nam; Department of Pulmonology, Thong Nhat Hospital, Ho Chi Minh City, Viet Nam
| | - Hung Song Nguyen
- College of Medicine, Taipei Medical University, Taipei, Taiwan; Wellcome Trust Major Overseas Program, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
| | - Dang Khanh Ngan Ho
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan
| | - Hung-Yuan Li
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yuan Lin
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Hsiao-Yean Chiu
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan; Research Center of Sleep Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yang-Ching Chen
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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23
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Gorący A, Rosik J, Szostak B, Ustianowski Ł, Ustianowska K, Gorący J. Human Cell Organelles in SARS-CoV-2 Infection: An Up-to-Date Overview. Viruses 2022; 14:v14051092. [PMID: 35632833 PMCID: PMC9144443 DOI: 10.3390/v14051092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/10/2022] [Accepted: 05/17/2022] [Indexed: 12/10/2022] Open
Abstract
Since the end of 2019, the whole world has been struggling with the life-threatening pandemic amongst all age groups and geographic areas caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). The Coronavirus Disease 2019 (COVID-19) pandemic, which has led to more than 468 million cases and over 6 million deaths reported worldwide (as of 20 March 2022), is one of the greatest threats to human health in history. Meanwhile, the lack of specific and irresistible treatment modalities provoked concentrated efforts in scientists around the world. Various mechanisms of cell entry and cellular dysfunction were initially proclaimed. Especially, mitochondria and cell membrane are crucial for the course of infection. The SARS-CoV-2 invasion depends on angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and cluster of differentiation 147 (CD147), expressed on host cells. Moreover, in this narrative review, we aim to discuss other cell organelles targeted by SARS-CoV-2. Lastly, we briefly summarize the studies on various drugs.
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Affiliation(s)
- Anna Gorący
- Independent Laboratory of Invasive Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (A.G.); (J.G.)
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Jakub Rosik
- Independent Laboratory of Invasive Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (A.G.); (J.G.)
- Department of Physiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (B.S.); (Ł.U.); (K.U.)
- Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA
- Correspondence:
| | - Bartosz Szostak
- Department of Physiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (B.S.); (Ł.U.); (K.U.)
| | - Łukasz Ustianowski
- Department of Physiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (B.S.); (Ł.U.); (K.U.)
| | - Klaudia Ustianowska
- Department of Physiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (B.S.); (Ł.U.); (K.U.)
| | - Jarosław Gorący
- Independent Laboratory of Invasive Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland; (A.G.); (J.G.)
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24
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Kastora S, Patel M, Carter B, Delibegovic M, Myint PK. Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta-analysis. Endocrinol Diabetes Metab 2022; 5:e00338. [PMID: 35441801 PMCID: PMC9094465 DOI: 10.1002/edm2.338] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/25/2022] [Accepted: 03/28/2022] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION To date, COVID-19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID-19 infection. Whether that holds true across world regions uniformly has not been previously assessed. METHODS This study offers the first umbrella systematic review and meta-analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID-19 hospitalization outcomes, were included. This meta-analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta-analysis reported, (2) no confirmed COVID-19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). RESULTS Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53-65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID-19-related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East-originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID-19 mortality, whilst the inverse was true for concurrent insulin use. CONCLUSIONS Whilst diabetes constitutes a poor prognosticator for various COVID-19 infection outcomes, variability across world regions is significant and may skew overall trends.
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Affiliation(s)
- Stavroula Kastora
- School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK
| | - Manisha Patel
- School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK
| | - Ben Carter
- Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Mirela Delibegovic
- Aberdeen Cardiovascular and Diabetes Centre (ACDC), Institute of Medical Sciences (IMS), University of Aberdeen, Aberdeen, UK
| | - Phyo Kyaw Myint
- Aberdeen Cardiovascular and Diabetes Centre (ACDC), Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
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25
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Dedov II, Mokrysheva NG, Shestakova MV, Nikonova TV, Mayorov AY, Galstyan GR, Shamhalova MS, Barysheva VO, Ametov AS, Antsiferov MB, Babenko AY, Bardymova TP, Valeeva FV, Vachugova AA, Grineva EN, Demidova TY, Kiseleva TP, Kunicyna MA, Markova TN, Mkrtumyan AM, Petunina NA, Ruyatkina LA, Saluhov VV, Suplotova LA, Hadarceva EL, Halimov YS. Glycemia control and choice of antihyperglycemic therapy in patients with type 2 diabetes mellitus and COVID-19: a consensus decision of the board of experts of the Russian association of endocrinologists. DIABETES MELLITUS 2022; 25:27-49. [DOI: 10.14341/dm12873] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
A dangerous viral disease COVID-19, caused by a new RNA coronavirus SARS-COV-2, has been actively spreading in the world since December 2019. The main manifestations of this disease are bilateral pneumonia, often accompanied by the development of acute respiratory syndrome and respiratory failure. Patients with diabetes mellitus (DM) are at high risk of infection with the SARS-COV-2 virus, severe illness and death.Maintaining of target glycemic levels is the most important factor in a favorable outcome of COVID-19 in both type 1 and type 2 DM. The choice of antihyperglycemic therapy in a patient with DM in the acute period of COVID-19 depends on the initial therapy, the severity of hyperglycemia, the severity of the viral infection and the patient’s clinical condition.The article presents the recommendations of the board of experts of the Russian Association of Endocrinologists on glycemic control and the choice of antihyperglycemic therapy in patients with type 2 DM and COVID-19, and also on the use of glucocorticosteroids used in the treatment of COVID-19 in patients with type 2 DM.
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Affiliation(s)
| | | | | | | | | | | | | | | | - A. S. Ametov
- Russian Medical Academy of Continuous Professional Education
| | - M. B. Antsiferov
- Russian Medical Academy of Continuous Professional Education; Endocrinological Dispensary of the Moscow City Health Department
| | | | - T. P. Bardymova
- Irkutsk State Medical Academy of Postgraduate Education — Branch Campus of the Russian Medical Academy of Continuous Professional Education
| | | | | | | | | | | | | | - T. N. Markova
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; Moscow City Clinical Hospital №52
| | - A. M. Mkrtumyan
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; A.S. Loginov Moscow Clinical Scientific Centre
| | - N. A. Petunina
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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26
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Chen JJ, Wu CY, Jenq CC, Lee TH, Tsai CY, Tu HT, Huang YT, Yen CL, Yen TH, Chen YC, Tian YC, Yang CW, Yang HY. Association of Glucagon-Like Peptide-1 Receptor Agonist vs Dipeptidyl Peptidase-4 Inhibitor Use With Mortality Among Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease. JAMA Netw Open 2022; 5:e221169. [PMID: 35254430 PMCID: PMC8902651 DOI: 10.1001/jamanetworkopen.2022.1169] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 01/13/2022] [Indexed: 12/25/2022] Open
Abstract
IMPORTANCE Glucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood. OBJECTIVE To assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021. EXPOSURES Treatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors. MAIN OUTCOMES AND MEASURES All-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups. RESULTS Of 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction). CONCLUSIONS AND RELEVANCE Treatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.
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Affiliation(s)
- Jia-Jin Chen
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chao-Yi Wu
- Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Chang-Chyi Jenq
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tao-Han Lee
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
| | - Chung-Ying Tsai
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hui-Tzu Tu
- Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yu-Tung Huang
- Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chieh-Li Yen
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tzung-Hai Yen
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yung-Chang Chen
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ya-Chung Tian
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Wei Yang
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Huang-Yu Yang
- Kidney Research Institute, Department of Nephrology, Chang Gung Memorial Hospital in Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
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Alshnbari A, Idris I. Can sodium-glucose co-transporter-2 (SGLT-2) inhibitor reduce the risk of adverse complications due to COVID-19? - Targeting hyperinflammation. Curr Med Res Opin 2022; 38:357-364. [PMID: 35057687 PMCID: PMC8787835 DOI: 10.1080/03007995.2022.2027141] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are antidiabetic drugs with numerous pleiotropic and positive clinical effects, particularly regarding a reno-cardiovascular protective effect. More recent studies, including from our laboratory, have highlighted some novel anti-inflammatory activity of SGLT-2 inhibitors. This may confer a theoretical advantage in mitigating excessive cytokine production and inflammatory response associated with serious COVID-19 infection. Specifically, earlier research has demonstrated that SGLT-2 inhibitors are associated with a notable decrease in inflammatory indicators, for example, C-reactive protein, ferritin, and interleukin-6. Furthermore, SGLT-2 inhibitors exhibit a favourable impact on the vascular endothelium function; this could pertinence the prophylaxis of the thrombotic issues that arise in SARS-CoV-2. This review provides an overview of the COVID-19 indirect immune response mechanisms impacting the cardiovascular system and the possible effect of SGLT-2 inhibitors on the management of COVID-19.
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Affiliation(s)
- Afnan Alshnbari
- Royal Derby Hospital Centre, University of Nottingham, Derby, UK
| | - Iskandar Idris
- Royal Derby Hospital Centre, University of Nottingham, Derby, UK
- MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, NIHR, Nottingham BRC, University of Nottingham, Nottingham, UK
- Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, UK
- CONTACT Iskandar Idris Royal Derby Hospital Centre, University of Nottingham, Uttoxeter Road, DerbyDE22 3DT, UK
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Alshanwani A, Kashour T, Badr A. Anti-Diabetic Drugs GLP-1 Agonists and DPP-4 Inhibitors may Represent Potential Therapeutic Approaches for COVID-19. Endocr Metab Immune Disord Drug Targets 2022; 22:571-578. [PMID: 34370655 DOI: 10.2174/1871530321666210809153558] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 01/08/2023]
Abstract
The fast spread of coronavirus 2019 (COVID-19) calls for immediate action to counter the associated significant loss of human life and deep economic impact. Certain patient populations like those with obesity and diabetes are at higher risk for acquiring severe COVID-19 disease and have a higher risk of COVID-19 associated mortality. In the absence of an effective and safe vaccine, the only immediate promising approach is to repurpose an existing approved drug. Several drugs have been proposed and tested as adjunctive therapy for COVID-19. Among these drugs are the glucagon-like peptide-1 (GLP-1) 2 agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors. Beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties, which include cardioprotective effects, anti-inflammatory and immunomodulatory activities, antifibrotic effects, antithrombotic effects, and vascular endothelial protective properties. This narrative review discusses these protective properties and addresses their scientific plausibility for their potential use as adjunctive therapy for COVID-19 disease.
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Affiliation(s)
- Aliah Alshanwani
- College of Medicine, Physiology Department, King Saud University, Riyadh, Saudi Arabia
| | - Tarek Kashour
- King Fahd Cardiac Centre, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Amira Badr
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Chen Y, Lv X, Lin S, Arshad M, Dai M. The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis. Front Endocrinol (Lausanne) 2022; 13:895458. [PMID: 35692410 PMCID: PMC9186017 DOI: 10.3389/fendo.2022.895458] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 04/19/2022] [Indexed: 02/05/2023] Open
Abstract
AIMS This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. METHODS We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis. RESULTS The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%. CONCLUSION Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin. SYSTEMATIC REVIEW REGISTRATION PROSPERO (CRD42021288200).
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Affiliation(s)
- Yidan Chen
- Department of Rheumatology & Immunology, West China Hospital of Sichuan University, Chengdu, China
| | - Xingfei Lv
- Department of Orthopedics, People’s Hospital of Zhongjiang County, Deyang, China
| | - Sang Lin
- Department of Rheumatology& Immunology, China-Japan Friendship Hospital, Beijing, China
| | - Mohammad Arshad
- Department of Pediatrics Surgery, Lok Nayak Hospital, New Delhi, India
| | - Mengjun Dai
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Mengjun Dai,
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Lee JH. Potential therapeutic effect of glucagon-like peptide-1 receptor agonists on COVID-19-induced pulmonary arterial hypertension. Med Hypotheses 2021; 158:110739. [PMID: 34916733 PMCID: PMC8654461 DOI: 10.1016/j.mehy.2021.110739] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/04/2021] [Accepted: 12/05/2021] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious diseases caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Now, it is pandemic over the world. SARS-CoV-2 often causes a “cytokine storm” in people with COVID-19, causing inflammatory lung damage and pneumonia, which eventually leads to death. Glucagon like peptide-1 (GLP-1) is well known as an incretin hormone responsible for regulation of blood glucose through its receptor. Beyond glycemic control, GLP-1 receptor agonists (GLP-1RAs) have promising anti-inflammatory actions in human and rodent pathological models. Recent studies proved that GLP-1RAs attenuate pulmonary inflammation, reduce cytokine production, and preserve lung function in mice and rats with experimental lung injury. Moreover, a thickened pulmonary vascular wall, an important characteristic of pulmonary arterial hypertension (PAH) was observed in the autopsy lung tissue of a COVID-19 patient. Thus GLP-1RAs may be a novel therapeutic strategy for combating this pandemic specifically for patient characteristics of PHA after COVID-19 infection.
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Affiliation(s)
- Jong Han Lee
- Department of Marine Bio and Medical Science, Hanseo University, Seosan, South Korea
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Zhang T, Tong X, Zhang S, Wang D, Wang L, Wang Q, Fan H. The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence. Front Pharmacol 2021; 12:731453. [PMID: 34955820 PMCID: PMC8696080 DOI: 10.3389/fphar.2021.731453] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 11/25/2021] [Indexed: 02/05/2023] Open
Abstract
CD26/Dipeptidyl peptidase 4 (DPP4) is a type II transmembrane glycoprotein that is widely expressed in various organs and cells. It can also exist in body fluids in a soluble form. DPP4 participates in various physiological and pathological processes by regulating energy metabolism, inflammation, and immune function. DPP4 inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus. More evidence has shown the role of DPP4 in the pathogenesis of lung diseases, since it is highly expressed in the lung parenchyma and the surface of the epithelium, vascular endothelium, and fibroblasts of human bronchi. It is a potential biomarker and therapeutic target for various lung diseases. During the coronavirus disease-19 (COVID-19) global pandemic, DPP4 was found to be an important marker that may play a significant role in disease progression. Some clinical trials on DPP4 inhibitors in COVID-19 are ongoing. DPP4 also affects other infectious respiratory diseases such as Middle East respiratory syndrome and non-infectious lung diseases such as pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and asthma. This review aims to summarize the roles of DPP4 and its inhibitors in infectious lung diseases and non-infectious diseases to provide new insights for clinical physicians.
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Affiliation(s)
| | | | | | | | | | | | - Hong Fan
- Department of Respiratory and Critical Care Medicine, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China
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Popovic DS, Papanas N, Pantea Stoian A, Rizvi AA, Janez A, Rizzo M. Use of Novel Antidiabetic Agents in Patients with Type 2 Diabetes and COVID-19: A Critical Review. Diabetes Ther 2021; 12:3037-3054. [PMID: 34699021 PMCID: PMC8546380 DOI: 10.1007/s13300-021-01170-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The latter is a pandemic that has the potential of developing into a severe illness manifesting as systemic inflammatory response syndrome, acute respiratory distress syndrome, multi-organ involvement and shock. In addition, advanced age and male sex and certain underlying health conditions, like type 2 diabetes mellitus (T2DM), predispose to a higher risk of greater COVID-19 severity and mortality. This calls for an urgent identification of antidiabetic agents associated with more favourable COVID-19 outcomes among patients with T2DM, as well as recognition of their potential underlying mechanisms. It is crucial that individuals with T2DM be kept under very stringent glycaemic control in order to avoid developing various cardiovascular, renal and metabolic complications associated with more severe forms of COVID-19 that lead to increased mortality. The use of novel antidiabetic agents dipeptidyl peptidase 4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) in subjects with T2DM may have beneficial effects on COVID-19 outcomes. However, relevant studies either show inconsistent results (DPP4i) or are still too few (SGLT2i and GLP-1RAs). Further research is therefore needed to assess the impact of these agents on COVID-19 outcomes.
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Affiliation(s)
- Djordje S Popovic
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Novi Sad, Serbia
- Medical Faculty, University of Novi Sad, Novi Sad, Serbia
| | - Nikolaos Papanas
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupoli, Greece
| | - Anca Pantea Stoian
- Faculty of Medicine, Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
| | - Ali A Rizvi
- Division of Endocrinology, Metabolism, and Lipids, Emory University School of Medicine, Atlanta, GA, USA
- Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC, USA
| | - Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Manfredi Rizzo
- Faculty of Medicine, Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC, USA
- Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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Banerjee Y, Pantea Stoian A, Silva-Nunes J, Sonmez A, Rizvi AA, Janez A, Rizzo M. The role of GLP-1 receptor agonists during COVID-19 pandemia: a hypothetical molecular mechanism. Expert Opin Drug Saf 2021; 20:1309-1315. [PMID: 34424130 PMCID: PMC8425441 DOI: 10.1080/14740338.2021.1970744] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 08/17/2021] [Indexed: 01/08/2023]
Abstract
INTRODUCTION A number of anti-diabetic treatments have been favored during the continuing spread of the current SARS-CoV-2 pandemic. Glucagon like peptide-1 receptor agonists (GLP1-RAs) are a group of antidiabetic drugs, the glucose reducing effect of which is founded on augmenting glucose-dependent insulin secretion with concomitant reduction of glucagon secretion and delayed gastric emptying. Apart from their glucose lowering effects, GLP1-RAs also exert a plethora of pleiotropic activities in the form of anti-inflammatory, anti-thrombotic and anti-obesogenic properties, with beneficial cardiovascular and renal impact. All these make this class of drugs a preferred option for managing patients with type 2 diabetes (T2D), and potentially helpful in those with SARS-CoV2 infection. AREAS COVERED In the present article we propose a hypothetical molecular mechanism by which GLP1-RAs may interact with SARS-CoV-2 activity. EXPERT OPINION The beneficial properties of GLP1-RAs may be of specific importance during COVID-19 infection for the most fragile patients with chronic comorbid conditions such as T2D, and those at higher cardiovascular and renal disease risk. Yet, further studies are needed to confirm our hypothesis and preliminary findings available in the literature.
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Affiliation(s)
- Yajnavalka Banerjee
- Biochemistry, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
- Centre of Medical Education, University of Dundee, UK
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - José Silva-Nunes
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário De Lisboa Central, Lisbon, Portugal
- Nova Medical School-Faculdade De Ciências Medicas, New University of Lisbon, Lisbon, Portugal
- Health and Technology Research Center (H&TRC), Escola Superior De Tecnologia Da Saude De Lisboa, Lisbon, Portugal
| | - Alper Sonmez
- Department of Endocrinology and Metabolism, Gulhane School of Medicine, University of Health Sciences, Ankara, Turkey
| | - Ali A Rizvi
- Division of Endocrinology, Metabolism, and Lipids Emory, University School of Medicine, Atlanta, GA, USA
- Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC, USA
| | - Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Faculty of Medicine, University of Ljubljana, Slovenia
| | - Manfredi Rizzo
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC, USA
- Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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Avogaro A, Bonora B, Fadini GP. Managing diabetes in diabetic patients with COVID: where do we start from? Acta Diabetol 2021; 58:1441-1450. [PMID: 34173070 PMCID: PMC8231743 DOI: 10.1007/s00592-021-01739-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 05/06/2021] [Indexed: 12/15/2022]
Abstract
AIMS COVID-19 has and still is sweeping away the national health systems worldwide. In this review, we sought to determine the evidence base proofs on the antidiabetic treatment capable to reduce the risk of COVID-19-related mortality. METHODS We have performed a systematic search of published articles using PubMed, and EMBASE from March 2020 to March 31st, 2021. We excluded editorials, commentary, letters to the editor, reviews, and studies that did not have mortality as an outcome. For metformin and insulin only, we performed a meta-analysis using Cochrane RevMan 5.2. RESULTS Among antidiabetic drugs, metformin was the only drug associated with a reduced risk of mortality. Conversely, insulin appears associated with an increased risk. The other classes of drugs were neutral. CONCLUSIONS The totality of articles reports retrospective data strongly affected by "channeling bias" so that most of the existing results on each class of drugs are driven by the phenotype of patients likely to receive that specific drug by prescription.
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Affiliation(s)
- Angelo Avogaro
- Department of Medicine, Unit of Metabolic Disease, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
| | - Benedetta Bonora
- Department of Medicine, Unit of Metabolic Disease, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
| | - Gian Paolo Fadini
- Department of Medicine, Unit of Metabolic Disease, University of Padova, Via Giustiniani 2, 35128, Padova, Italy
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Papadopoulos VP, Koutroulos MV, Zikoudi DG, Bakola SA, Avramidou P, Touzlatzi N, Filippou DK. Diabetes-related acute metabolic emergencies in COVID-19 patients: a systematic review and meta-analysis. Diabetol Int 2021; 12:445-459. [PMID: 33777611 PMCID: PMC7985576 DOI: 10.1007/s13340-021-00502-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 03/16/2021] [Indexed: 02/07/2023]
Abstract
AIMS COVID-19 is associated with diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and euglycaemic DKA (EDKA); however, evidence regarding parameters affecting outcome and mortality rates is scarce. METHODS A systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 2020 to 7 January 2021 to identify all studies describing clinical profile, outcome and mortality rates regarding DKA, HHS, DKA/HHS and EDKA cases in COVID-19 patients. The appropriate Joanna Briggs Institute tools were used for quality assessment; quality of evidence was approached using GRADE. Univariate and multivariate analyses were used to assess correlations between clinical characteristics and outcome based on case reports. Combined mortality rates (CMR) were estimated from data reported in case report series, cross-sectional studies, and meta-analyses. The protocol was submitted to PROSPERO (ID: 229356/230737). RESULTS From 312 identified publications, 44 were qualitatively and quantitatively analyzed. Critical COVID-19 necessitating ICU (P = 3 × 10-8), DKA/HHS presence (P = 0.021), and AKI (P = 0.037) were independently correlated with death. Increased COVID-19 severity (P = 0.003), elevated lactates (P < 0.001), augmented anion gap (P < 0.001), and AKI (P = 0.002) were associated with DKA/HHS. SGLT-2i were linked with EDKA (P = 0.004) and negatively associated with AKI (P = 0.023). CMR was 27.1% (95% CI 11.2-46.9%) with considerable heterogeneity (I 2 = 67%). CONCLUSION Acute diabetes-related metabolic emergencies in COVID-19 patients lead to increased mortality; key determinants are critical COVID-19 illness, coexistence of DKA/HHS and AKI. Previous SGLT-2i treatment, though associated with EDKA, might preserve renal function in COVID-19 patients. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s13340-021-00502-9.
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Affiliation(s)
- Vasileios P. Papadopoulos
- Department of Internal Medicine, Xanthi General Hospital, Xanthi, Greece
- First Department of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
- ENARGEIA” Medical Ltd, 6 Elpidos str, Xanthi, Greece
| | | | | | | | - Peny Avramidou
- Department of Internal Medicine, Xanthi General Hospital, Xanthi, Greece
| | - Ntilara Touzlatzi
- Department of Internal Medicine, Xanthi General Hospital, Xanthi, Greece
| | - Dimitrios K. Filippou
- Department of Anatomy and Surgical Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Czupryniak L, Dicker D, Lehmann R, Prázný M, Schernthaner G. The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence? Cardiovasc Diabetol 2021; 20:198. [PMID: 34598700 PMCID: PMC8485772 DOI: 10.1186/s12933-021-01389-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 09/20/2021] [Indexed: 12/15/2022] Open
Abstract
Patients with Covid-19 place new challenges on the management of type 2 diabetes, including the questions of whether glucose-lowering therapy should be adjusted during infection and how to manage a return to normal care after resolution of Covid-19 symptoms. Due to the sudden onset of the pandemic, physicians have by necessity made such important clinical decisions in the absence of robust evidence or consistent guidelines. The risk to patients is compounded by the prevalence of cardiovascular disease in this population, which alongside diabetes is a major risk factor for severe disease and mortality in Covid-19. We convened as experts from the Central and Eastern European region to consider what advice we can provide in the setting of type 2 diabetes and Covid-19, considering the evidence before, during and after infection. We review recommendations that have been published to date, and consider the best available—but currently limited—evidence from large observational studies and the DARE-19 randomized control trial. Notably, we find a lack of guidance on restarting patients on optimal antidiabetic therapy after recovering from Covid-19, and suggest that this may provide an opportunity to optimize treatment and counter clinical inertia that predates the pandemic. Furthermore, we emphasize that optimization applies not only to glycaemic control, but other factors such as cardiorenal protection. While we look forward to the emergence of new evidence that we hope will address these gaps, in the interim we provide a perspective, based on our collective clinical experience, on how best to manage glucose-lowering therapy as patients with Covid-19 recover from their disease and return to normal care.
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Affiliation(s)
- Leszek Czupryniak
- Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - Dror Dicker
- Department of Internal Medicine D, Hasharon Hospital, Rabin Medical Centre, Petah Tikva, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Roger Lehmann
- Department of Endocrinology, Diabetes and Nutrition, University Hospital Zürich, Zürich, Switzerland
| | - Martin Prázný
- 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic
| | - Guntram Schernthaner
- Department of Medicine I, Rudolfstiftung Hospital Vienna, 1030, Vienna, Austria. .,Medical University of Vienna, Vienna, Austria.
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Latosinska A, Siwy J, Cherney DZ, Perkins BA, Mischak H, Beige J. SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: An in-silico proof-of-principle of proteomics-based drug repurposing. Proteomics 2021; 21:e2100160. [PMID: 34477316 PMCID: PMC8646299 DOI: 10.1002/pmic.202100160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 08/31/2021] [Indexed: 01/08/2023]
Abstract
Severe COVID‐19 is reflected by significant changes in urine peptides. Based on this observation, a clinical test predicting COVID‐19 severity, CoV50, was developed and registered as in vitro diagnostic in Germany. We have hypothesized that molecular changes displayed by CoV50, likely reflective of endothelial damage, may be reversed by specific drugs. Such an impact by a drug could indicate potential benefits in the context of COVID‐19. To test this hypothesis, urinary peptide data from patients without COVID‐19 prior to and after drug treatment were collected from the human urinary proteome database. The drugs chosen were selected based on availability of sufficient number of participants in the dataset (n > 20) and potential value of drug therapies in the treatment of COVID‐19 based on reports in the literature. In these participants without COVID‐19, spironolactone did not demonstrate a significant impact on CoV50 scoring. Empagliflozin treatment resulted in a significant change in CoV50 scoring, indicative of a potential therapeutic benefit. The study serves as a proof‐of‐principle for a drug repurposing approach based on human urinary peptide signatures. The results support the initiation of a randomized control trial testing a potential positive effect of empagliflozin for severe COVID‐19, possibly via endothelial protective mechanisms.
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Affiliation(s)
| | | | - David Z Cherney
- Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Bruce A Perkins
- Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | | | - Joachim Beige
- Department of Nephrology and Kuratorium for Dialysis and Transplantation (KfH) Renal Unit, Hospital St. Georg, Leipzig, Germany.,Department of Internal Medicine 2 (Nephrology, Rheumatology, Endocrinology), Martin-Luther-University Halle/Wittenberg, Halle, Germany
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Al-Kuraishy HM, Al-Gareeb AI, Qusty N, Alexiou A, Batiha GES. Impact of Sitagliptin in Non-Diabetic Covid-19 Patients. Curr Mol Pharmacol 2021; 15:683-692. [PMID: 34477540 DOI: 10.2174/1874467214666210902115650] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/09/2021] [Accepted: 06/14/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVE In Coronavirus disease 2019 (Covid-19), SARS-CoV-2 may use dipeptidyl peptidase 4 (DPP4) as an entry-point in different tissues expressing these receptors. DPP4 inhibitors (DPP4Is), also named gliptins like sitagliptin, have anti-inflammatory and antioxidant effects; thereby lessen inflammatory and oxidative stress in diabetic Covid-19 patients. Therefore, the present study aimed to illustrate the potential beneficial effect of sitagliptin in managing Covid-19 in non-diabetic patients. METHODS A total number of 89 patients with Covid-19 were recruited from a single-center at the time of diagnosis. The recruited patients were assigned according to the standard therapy for Covid-19 and our interventional therapy into two groups; Group A: Covid-19 patients on the standard therapy (n=40) and Group B: Covid-19 patients on the standard therapy plus sitagliptin (n=49). The duration of this interventional study was 28 days according to the guideline in management patients with Covid-19. Routine laboratory investigations, serological tests, complete blood count (CBC), C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), and serum ferritin were measured to observed Covid-19 severity and complications. Lung computed tomography (CT) and clinical scores were evaluated. RESULTS The present study illustrated that sitagliptin add-on standard therapy improved clinical outcomes, radiological scores, and inflammatory biomarkers than standard therapy alone in non-diabetic patients with Covid-19 (P<0.01). CONCLUSIONS Sitagliptin add-on standard therapy in managing non-diabetic Covid-19 patients may have a robust beneficial effect by modulating inflammatory cytokines with subsequent good clinical outcomes.
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Affiliation(s)
- Hayder M Al-Kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad. Iraq
| | - Ali I Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad. Iraq
| | - Naeem Qusty
- Medical Laboratories Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca. Saudi Arabia
| | | | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt
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Su YC, Shao SC, Lai ECC, Lee CN, Hung MJ, Lai CC, Hsu SM, Hung JH. Risk of diabetic macular oedema with sodium-glucose cotransporter-2 inhibitors in type 2 diabetes patients: A multi-institutional cohort study in Taiwan. Diabetes Obes Metab 2021; 23:2067-2076. [PMID: 34047442 DOI: 10.1111/dom.14445] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/18/2021] [Accepted: 05/23/2021] [Indexed: 12/19/2022]
Abstract
AIMS To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS We conducted a retrospective cohort study by analysing a large multi-institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. RESULTS We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61-81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4-108.7] mL/min/1.73 m2 and urine albumin-creatinine ratio [UACR] 26.1 [9.7-117.6] mg/g) and 1067 new users of GLP-1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64-84] mmol/mol, eGFR 91.6 [68.6-114.0] mL/min/1.73 m2 and UACR 37.6 [11.1-153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person-years), compared to those receiving GLP-1RAs (10.7/1000 person-years) with an HR of 0.75 (95% CI 0.64-0.88). CONCLUSIONS Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP-1RAs. Future studies are necessary to confirm this observation.
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Affiliation(s)
- Yu-Chen Su
- Department of Ophthalmology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chieh Shao
- Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chaw-Ning Lee
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Jui Hung
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chi-Chun Lai
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Sheng-Min Hsu
- Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jia-Horung Hung
- Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Hariyanto TI, Intan D, Hananto JE, Putri C, Kurniawan A. Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression. Diabetes Res Clin Pract 2021; 179:109031. [PMID: 34461139 PMCID: PMC8397482 DOI: 10.1016/j.diabres.2021.109031] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 08/20/2021] [Accepted: 08/26/2021] [Indexed: 12/13/2022]
Abstract
AIMS GLP-1RA has many beneficial properties, including anti-inflammatory, anti-obesogenic, pulmonary protective effects as well as beneficial impact on gut microbiome. However, the evidence regarding the benefit of GLP-1RA in Covid-19 patients with diabetes is still unclear. This study sought to analyze the benefit of pre-admission use of GLP-1RA in altering the mortality outcomes of coronavirus disease 2019 (Covid-19) patients with diabetes mellitus. METHODS Using specific keywords, we comprehensively searched the potential articles on PubMed, Europe PMC, and medRxiv database until June 12th, 2021. All published studies on Covid-19 and GLP-1RA were retrieved. Statistical analysis was conducted using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. RESULTS A total of 9 studies with 19,660 diabetes mellitus patients who were infected by SARS-CoV-2 were included in the meta-analysis. Our data suggested that pre-admission use of GLP-1RA was associated with reduction in mortality rate from Covid-19 in patients with diabetes mellitus (OR 0.53; 95 %CI: 0.43-0.66, p < 0.00001, I2 = 0%, random-effect modelling). Further analysis showed that the associations were not influenced by age (p = 0.213), gender (p = 0.421), hypertension (p = 0.131), cardiovascular disease (p = 0.293), nor the use of metformin (p = 0.189) and insulin (p = 0.117). CONCLUSIONS Our study suggests that pre-admission use of GLP-1RA may offer beneficial effects on Covid-19 mortality in patients with diabetes mellitus. However, more randomized clinical trials are required to confirm this conclusion.
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Affiliation(s)
| | - Denny Intan
- Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang 15811, Indonesia
| | - Joshua Edward Hananto
- Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang 15811, Indonesia
| | - Cynthia Putri
- Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang 15811, Indonesia
| | - Andree Kurniawan
- Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Karawaci, Tangerang 15811, Indonesia.
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D'Onofrio L, Coraggio L, Zurru A, Carlone A, Mignogna C, Moretti C, Maddaloni E, Buzzetti R. Short-term safety profile of Sars-Cov2 vaccination on glucose control: Continuous glucose monitoring data in people with autoimmune diabetes. Diabetes Res Clin Pract 2021; 179:109022. [PMID: 34450248 PMCID: PMC8383474 DOI: 10.1016/j.diabres.2021.109022] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/16/2021] [Accepted: 08/19/2021] [Indexed: 11/22/2022]
Abstract
In patients with autoimmune diabetes no significant differences were observed in glucose control, expressed as time in range evaluated by continuous glucose monitoring comparing the 3 days after Sars-Cov2 vaccine with the 14 days preceding the vaccine.
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Affiliation(s)
- Luca D'Onofrio
- Experimental Medicine Department, Sapienza University of Rome, Italy.
| | - Lucia Coraggio
- Experimental Medicine Department, Sapienza University of Rome, Italy
| | - Annalisa Zurru
- Experimental Medicine Department, Sapienza University of Rome, Italy
| | - Angela Carlone
- Experimental Medicine Department, Sapienza University of Rome, Italy
| | - Carmen Mignogna
- Experimental Medicine Department, Sapienza University of Rome, Italy
| | - Chiara Moretti
- Experimental Medicine Department, Sapienza University of Rome, Italy
| | - Ernesto Maddaloni
- Experimental Medicine Department, Sapienza University of Rome, Italy
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Patoulias D, Doumas M. Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies. Endocrinol Metab (Seoul) 2021; 36:904-908. [PMID: 34311543 PMCID: PMC8419608 DOI: 10.3803/enm.2021.1048] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.
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Affiliation(s)
- Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, General Hospital “Hippokration”, Aristotle University of Thessaloniki, Thessaloniki,
Greece
| | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, General Hospital “Hippokration”, Aristotle University of Thessaloniki, Thessaloniki,
Greece
- Veterans Affairs Medical Center, George Washington University, Washington, DC,
USA
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43
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Han T, Ma S, Sun C, Zhang H, Qu G, Chen Y, Cheng C, Chen EL, Ayaz Ahmed M, Kim KY, Manem R, Chen M, Guo Z, Yang H, Yan Y, Zhou Q. The Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis. Arch Med Res 2021; 53:186-195. [PMID: 34412904 PMCID: PMC8349690 DOI: 10.1016/j.arcmed.2021.08.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/26/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Tiantian Han
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province, China
| | - Shaodi Ma
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province, China
| | - Chenyu Sun
- Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, USA.
| | - Huimei Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province, China
| | - Guangbo Qu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province, China
| | - Yue Chen
- Department of Clinical Medicine, School of the First Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, China
| | - Ce Cheng
- The University of Arizona College of Medicine at South Campus, Tucson, AZ, USA
| | - Eric L Chen
- Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, USA
| | - Mubashir Ayaz Ahmed
- Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, USA
| | - Keun Young Kim
- Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, USA
| | - Raveena Manem
- Internal Medicine, AMITA Health Saint Joseph Hospital Chicago, Chicago, Illinois, USA
| | - Mengshi Chen
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China
| | - Zhichun Guo
- Massachusetts college of Pharmacy and Health sciences, Boston, MA, USA
| | - Hongru Yang
- Massachusetts college of Pharmacy and Health sciences, Boston, MA, USA
| | - Yue Yan
- Massachusetts college of Pharmacy and Health sciences, Boston, MA, USA
| | - Qin Zhou
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
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Sarkar S, Das D, Borsingh Wann S, Kalita J, Manna P. Is diabetes mellitus a wrongdoer to COVID-19 severity? Diabetes Res Clin Pract 2021; 178:108936. [PMID: 34217771 PMCID: PMC8247195 DOI: 10.1016/j.diabres.2021.108936] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 05/25/2021] [Accepted: 06/29/2021] [Indexed: 01/08/2023]
Abstract
The coronavirus disease 19 (COVID-19) has turned out to be a pandemic in short period of time due to the high transmissibility of its causative agent, severe acute respiratory syndrome coronavirus 2. Various reports have suggested the promising link between overexpression of angiotensin converting enzyme 2 (ACE2) and COVID-19 pathogenesis. The severity of COVID-19 pathophysiology is greatly depended on several comorbidities, like hypertension, diabetes mellitus (DM), respiratory and cardiovascular disease, out of which DM has emerged as a major risk factor. The current review focuses on the link among the expression of ACE2, use of ACE inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), and risk of COVID-19 pathogenesis in DM. The review also emphasizes on synergistic detrimental effect of DM and COVID-19 on the immune system in provoking uncontrolled cytokine storm which eventually leads to lethal consequences. Finally, several possible therapeutic strategies have been highlighted to reduce the excess of risk associated with COVID-19 in people with DM.
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Affiliation(s)
- Sanjib Sarkar
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Dibyendu Das
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Sawlang Borsingh Wann
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Jatin Kalita
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Research Planning and Business Development Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India.
| | - Prasenjit Manna
- Biotechnology Group, Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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45
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Effects of the Na +/H + Ion Exchanger on Susceptibility to COVID-19 and the Course of the Disease. JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM : JRAAS 2021. [PMID: 34285709 DOI: 10.1155/2021/4754440.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The Na+/H+ ion exchanger (NHE) pumps Na+ inward the cell and H+ ion outside the cell. NHE activity increases in response to a decrease in intracellular pH, and it maintains intracellular pH in a narrow range. Patients with obesity, diabetes, and hypertension and the elderly are prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The angiotensin II (Ang II) level is high in chronic diseases such as diabetes, hypertension, and obesity. Ang II is the main stimulator of NHE, and an increased Ang II level causes prolonged NHE activation in these patients. The long-term increase in NHE activity causes H+ ions to leave the cell in patients with diabetes, hypertension, and obesity. Increasing H+ ions outside the cell lead to an increase in oxidative stress and reactive oxygen species. H+ ion flows into the cell due to the increased oxidative stress. This vicious circle causes intracellular pH to drop. Although NHE is activated when intracellular pH decreases, there is prolonged NHE activation in chronic diseases such as aforementioned. Novel coronavirus disease 2019 (COVID-19) progression may be more severe and mortal in these patients. SARS-CoV-2 readily invades the cell at low intracellular pH and causes infection. The renin-angiotensin system and NHE play a vital role in regulating intracellular pH. The reduction of NHE activity or its prolonged activation may cause susceptibility to SARS-CoV-2 infection by lowering intracellular pH in patients with diabetes, hypertension, and obesity. Prolonged NHE activation in these patients with COVID-19 may worsen the course of the disease. Scientists continue to investigate the mechanism of the disease and the factors that affect its clinical progression.
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46
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Schernthaner G. Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19 (Diabetes Metab J 2021;45:251-9). Diabetes Metab J 2021; 45:615-616. [PMID: 34352990 PMCID: PMC8369206 DOI: 10.4093/dmj.2021.0081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Guntram Schernthaner
- Department of Medicine, Medical University of Vienna, Vienna, Austria
- Corresponding author: Guntram Schernthaner https://orcid.org/0000-0003-2397-4468 Department of Medicine, Medical University of Vienna, 1180 Währinger Gürtel, Vienna, Austria E-mail:
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47
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Kahkoska AR, Abrahamsen TJ, Alexander GC, Bennett TD, Chute CG, Haendel MA, Klein KR, Mehta H, Miller JD, Moffitt RA, Stürmer T, Kvist K, Buse JB. Association Between Glucagon-Like Peptide 1 Receptor Agonist and Sodium-Glucose Cotransporter 2 Inhibitor Use and COVID-19 Outcomes. Diabetes Care 2021; 44:1564-1572. [PMID: 34135013 PMCID: PMC8323175 DOI: 10.2337/dc21-0065] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/23/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS We analyzed observational data from SARS-CoV-2-positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018-February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60-day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37-0.80] and 0.66 [0.50-0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS Among SARS-CoV-2-positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.
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Affiliation(s)
- Anna R Kahkoska
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | | | - G Caleb Alexander
- Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.,Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, MD
| | - Tellen D Bennett
- Section of Informatics and Data Science, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Christopher G Chute
- Schools of Medicine, Public Health, and Nursing, Johns Hopkins University, Baltimore, MD
| | - Melissa A Haendel
- Center for Health AI, University of Colorado School of Medicine, Aurora, CO
| | - Klara R Klein
- Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Hemalkumar Mehta
- Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Joshua D Miller
- Division of Endocrinology and Metabolism, Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY
| | - Richard A Moffitt
- Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY
| | - Til Stürmer
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | | | - John B Buse
- Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC .,NC Translational and Clinical Sciences Institute, University of North Carolina School of Medicine, Chapel Hill, NC
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48
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Cumhur Cure M, Cure E. Effects of the Na +/H + Ion Exchanger on Susceptibility to COVID-19 and the Course of the Disease. J Renin Angiotensin Aldosterone Syst 2021; 2021:4754440. [PMID: 34285709 PMCID: PMC8265032 DOI: 10.1155/2021/4754440] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/14/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
The Na+/H+ ion exchanger (NHE) pumps Na+ inward the cell and H+ ion outside the cell. NHE activity increases in response to a decrease in intracellular pH, and it maintains intracellular pH in a narrow range. Patients with obesity, diabetes, and hypertension and the elderly are prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The angiotensin II (Ang II) level is high in chronic diseases such as diabetes, hypertension, and obesity. Ang II is the main stimulator of NHE, and an increased Ang II level causes prolonged NHE activation in these patients. The long-term increase in NHE activity causes H+ ions to leave the cell in patients with diabetes, hypertension, and obesity. Increasing H+ ions outside the cell lead to an increase in oxidative stress and reactive oxygen species. H+ ion flows into the cell due to the increased oxidative stress. This vicious circle causes intracellular pH to drop. Although NHE is activated when intracellular pH decreases, there is prolonged NHE activation in chronic diseases such as aforementioned. Novel coronavirus disease 2019 (COVID-19) progression may be more severe and mortal in these patients. SARS-CoV-2 readily invades the cell at low intracellular pH and causes infection. The renin-angiotensin system and NHE play a vital role in regulating intracellular pH. The reduction of NHE activity or its prolonged activation may cause susceptibility to SARS-CoV-2 infection by lowering intracellular pH in patients with diabetes, hypertension, and obesity. Prolonged NHE activation in these patients with COVID-19 may worsen the course of the disease. Scientists continue to investigate the mechanism of the disease and the factors that affect its clinical progression.
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Affiliation(s)
- Medine Cumhur Cure
- Department of Biochemistry, Private Kucukcekmece Hospital, Istanbul, Turkey
| | - Erkan Cure
- Department of Internal Medicine, Ota&Jinemed Hospital, Istanbul, Turkey
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Schernthaner G. Can glucose-lowering drugs affect the prognosis of COVID-19 in patients with type 2 diabetes? Lancet Diabetes Endocrinol 2021; 9:251-252. [PMID: 33798462 PMCID: PMC8009615 DOI: 10.1016/s2213-8587(21)00059-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 03/01/2021] [Indexed: 12/21/2022]
Affiliation(s)
- Guntram Schernthaner
- Department of Medicine I, Rudolfstiftung Hospital Vienna, Vienna A 1030, Austria; Medical University of Vienna, Vienna, Austria.
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Zhao LM, Chen XH, Qiu M. Commentary: Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2021; 12:825100. [PMID: 35082762 PMCID: PMC8785330 DOI: 10.3389/fendo.2021.825100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/15/2021] [Indexed: 12/02/2022] Open
Affiliation(s)
- Li-Min Zhao
- Department of Geriatric Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
| | - Xie-Hui Chen
- Department of Geriatric Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
- *Correspondence: Xie-Hui Chen, ; Mei Qiu,
| | - Mei Qiu
- Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China
- *Correspondence: Xie-Hui Chen, ; Mei Qiu,
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