Obesity and Type 2 Diabetes Mellitus (T2DM) are interrelated chronic conditions whose global prevalence continues to rise, posing significant clinical and socioeconomic challenges. Their pathophysiological intersection-commonly referred to as "diabesity"-is sustained by a complex interplay of mechanisms, including visceral adipose tissue inflammation, macrophage polarization, disrupted insulin signaling, and adipokine imbalance. These processes contribute to chronic low-grade systemic inflammation, impair pancreatic β-cell function, and exacerbate glucose intolerance. This review critically explores the mechanistic connections between obesity and T2DM, with a focus on recent advances in pharmacological therapies-such as GLP-1 receptor agonists, SGLT2 inhibitors, and dual GIP/GLP-1 receptor agonists-alongside evidence-based lifestyle modifications and bariatric procedures. By integrating current translational and clinical findings, we aim to provide a comprehensive perspective to support the development of more effective and individualized treatment strategies for diabesity.

Inhibitors of the Sodium/Glucose co-transporter 2 (SGLT2) have been evolving into an important contribution to the treatment of diabetes mellitus. As the inhibition of SGLT2 is sensitive to the structural configuration at the sugar moiety of the inhibitors, it is of high interest to provide in silico-based methods for the prediction of the activity of potential SGLT2 inhibitors that take three-dimensional information into account. To attain this objective, a classification model based on the docking scores obtained from the best-performing docking-based virtual screening was created. Furthermore, the impact of ensemble docking using docking results from five SGLT2 structures and the incorporation of structural similarity information was assessed by creating classification models using these approaches. Taking a combined approach of docking score and structural similarity modelling led to the best performance with a Matthews Correlation Coefficient (MCC) of 0.64. Finally, to explore the ability of the used docking algorithms to correctly predict the influence of different three-dimensional information, a library of molecules with a negatively contributing configuration was created and docked, showing decreased docking scores for the molecule library with a disadvantaged configuration.

In the era of sodium-glucose cotransporter 2 (SGLT2) inhibitors, population-wide screening for chronic kidney disease (CKD) may provide good value, yet implications across racial and ethnic groups are unknown.

To evaluate the health outcomes, costs, and cost-effectiveness of population-wide CKD screening for 4 racial and ethnic groups.

In this cost-effectiveness analysis, a decision-analytic Markov model was separately calibrated to simulate CKD progression among simulated cohorts of US Hispanic adults, non-Hispanic Black adults, non-Hispanic White adults, and adults who belong to additional racial and ethnic groups (ie, Asian and multiracial individuals and those self-reporting other race and ethnicity). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and Centers for Medicare & Medicaid Services data. Analyses were conducted from January 1, 2023, to November 6, 2024.

One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated between age 35 and 75 years, with and without addition of SGLT2 inhibitors to angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy for CKD.

Lifetime cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); discounted life-years (LYs), quality-adjusted LYs (QALYs), lifetime health care costs (in 2024 US dollars), and incremental cost-effectiveness ratios.

Under the status quo, non-Hispanic Black adults aged 35 years had the highest lifetime incidence of kidney failure requiring KRT (6.2% [95% UI, 2.8%-10.6%]) compared with Hispanic adults (3.6% [95% UI, 1.1%-6.7%]), non-Hispanic White adults (2.3% [95% UI, 0.4%-5.2%]), and adults from additional racial and ethnic groups (3.3% [95% UI, 1.2%-6.5%]). Screening every 5 years from ages 55 to 75 years combined with SGLT2 inhibitors reduced incidence of KRT and increased LYs across all racial and ethnic groups, with the largest average changes observed for non-Hispanic Black adults (0.8-percentage point decrease and 0.19-year increase). Every 5-year screening from age 55 to 75 years cost $99 100/QALY gained for the overall population and less than $150 000/QALY gained across racial and ethnic groups, with the lowest cost observed for non-Hispanic Black adults ($73 400/QALY gained). Screening starting at age 35 years was only cost-effective for non-Hispanic Black adults ($115 000/QALY gained).

In this cost-effectiveness analysis, population-wide screening for CKD from ages 55 to 75 years was projected to improve population health, was cost-effective, and reduced disparities across 4 racial and ethnic groups. Starting population-wide screening at younger ages was projected to further benefit non-Hispanic Black adults.

Systemic autoimmune rheumatic disease (SARD) patients have been excluded from sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials given putative risks, but this risk magnitude is unknown. We aimed to quantify SGLT2i adverse event risks among patients with vs. without SARD.   METHODS: In a retrospective cohort study, patients with SARD at Mass General Brigham, a multihospital system in Boston, Massachusetts, prescribed SGLT2i were age-, self-reported race-, and sex-matched to patients prescribed the same SGLT2i between 1/1/2016 and 12/10/2021. Cumulative incidence and Cox models, overall and sex-stratified, estimated patient-reported adverse event risks from prescription date, censoring for discontinuation, death, or study end (12/12/2022).

Four hundred sixty-eight SARD and 420 matched non-SARD patients were compared: mean age 64 years (SD 11.3), 61% female, and 70% White. SARD patients had shorter SGLT2i use duration (8.4 vs. 12.7 months; p < 0.0001) and time to adverse event (0.59 vs. 0.85 years; p 0.04). Yeast infections (9.8% vs. 6.2%; p 0.047) and muscular symptoms (3.4% vs. 1.0%, p 0.01) were more prevalent among those with SARD. Adjusting for baseline demographics, adverse event risk was higher (MV HR 1.68; 95% CI 1.28, 2.21), in patients with vs. without SARD. Risk was higher in women than men overall and in women with SARD vs. without (adjusted HR 1.86; 95% CI 1.36, 2.54).

Patients with vs. without SARD had 68% higher adverse event risk with SGLT2i use. Women with vs. without SARD had > 85% higher adverse event risks, although most were not serious. Trials of safety and efficacy of SGLT2i among SARD patients are warranted. Key Points •To our knowledge, this is the first study to compare adverse events associated with SGLT2i utilization in patients with vs. without SARD, despite RCT exclusion and documented SGLT2i use in the population. •In our comparison of 468 patients with SARD and 420 patients without, we identified a greater than 65% increase in risk of adverse event outcomes among patients with SARD. •Furthermore, we found that this risk disproportionately affected female patients, with a 4.4-fold increased risk among women with SARD compared to men without.

We aimed to investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) in patients with type 2 diabetes mellitus (T2DM) in clinical practice.

A total of 340 patients were included. Data on age, gender, antidiabetic medications, and bioanalytical parameters were collected at baseline and one year later. Were analyzed estimated glomerular filtration rate (eGFR), blood sodium and potassium levels, blood pressure, weight, cardiovascular risk, and glycated hemoglobin (HbA1c).

Patients treated with SGLT2i exhibited a significant improvement in eGFR at the endpoint compared to baseline (p = 0.006). Both treatment groups experienced reductions in systolic blood pressure at the endpoint; especially patients treated with SGLT2i (p = 0.0002). GLP1RA treatment resulted in a statistically significant weight reduction from baseline to endpoint (p < 0.0001), with a higher percentage of patients achieving ≥ 5% weight loss compared to the non-GLP1RA group (33.6% vs. 19.8%). Both SGLT2i and GLP1RA treatments significantly reduced cardiovascular risk scores (p = 0.004 and p = 0.002, respectively). Additionally, both treatments were associated with a significant reduction in HbA1c levels at the endpoint (p = 0.010 and p = 0.002, respectively).

Our findings suggest that SGLT2i and GLP1RA offer beneficial effects in patients with T2DM.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have changed clinical management of chronic kidney disease (CKD) and made populationwide screening for CKD a viable strategy. Optimal age of screening initiation has yet to be evaluated.

To compare the clinical benefits, costs, and cost-effectiveness of population-wide CKD screening at different initiation ages and screening frequencies.

This cost-effectiveness study used a previously published decision-analytic Markov cohort model that simulated progression of CKD among US adults from age 35 years and older and was calibrated to population-level data from the National Health and Nutrition Examination Survey (NHANES). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and US Centers for Medicare & Medicaid Services data. Analyses were performed from June 2023 through September 2024.

One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated at ages between 35 and 75 years, with and without addition of SGLT2 inhibitors to conventional CKD therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers).

Cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); life years, quality-adjusted life years (QALYs), lifetime health care costs (2024 US currency), and incremental cost-effectiveness ratios discounted at 3% annually.

For those aged 35 years, starting screening at age 55 years, and continuing every 5 years through age 75 years, combined with SGLT2 inhibitors, decreased the cumulative incidence of kidney failure requiring KRT from 2.4% to 1.9%, increased life expectancy by 0.13 years, and cost $128 400 per QALY gained. Although initiation of screening every 5 years at age 35 or 45 years yielded greater gains in population-wide health benefits, these strategies cost more than $200 000 per additional QALY gained. The comparative values of starting screening at different ages were sensitive to the cost and effectiveness of SGLT2 inhibitors; if SGLT2 inhibitor prices drop due to patent expirations, screening at age 55 years continued to be cost-effective even if SGLT2 inhibitor effectiveness were 30% lower than in the base case.

This study found that, based on conventional benchmarks for cost-effectiveness in medicine, initiating population-wide CKD screening with SGLT2 inhibitors at age 55 years would be cost-effective.

Obesity and type 2 diabetes mellitus are closely associated with each other and require careful management. This study aimed to assess the impact of sodium-glucose co-transporter 2 (SGLT2) inhibitors on glycemic control and body composition in diabetic patients, stratified by obesity status.

We enrolled patients diagnosed with type 2 diabetes mellitus, categorized as obese (BMI≥30) or non-obese (BMI<30), from our outpatient clinic. SGLT2 inhibitor therapy was added to their existing treatment regimen without altering dietary habits or exercise routines. Anthropometric measurements and laboratory parameters were compared between baseline and the third month of treatment.

The study included 40 participants, evenly split between obese and non-obese groups. At the third-month follow-up, significant reductions were observed in BMI, weight, waist and hip circumference, and body fat percentage across both groups (p < 0.001). Conversely, muscle mass percentage significantly increased (p < 0.001). Additionally, there were statistically significant decreases in HbA1c, glucose, CRP, ALT, LDL, and total cholesterol levels from baseline to the third month of treatment (p < 0.001 for HbA1c and glucose; p = 0.009, p = 0.022, p = 0.003, and p = 0.021, respectively, for CRP, ALT, LDL, and total cholesterol).

The findings of the present study suggest that SGLT2 inhibitors may offer substantial benefits, particularly in the management of obesity-related type 2 diabetes.

Diabetes is a chronic endocrine disorder that negatively affects various body systems, including the nervous system. Diabetes can cause or exacerbate various neurological disorders, and diabetes-induced neurodegeneration can involve several mechanisms such as mitochondrial dysfunction, activation of oxidative stress, neuronal inflammation, and cell death. In recent years, the management of diabetes-induced neurodegeneration has relied on several types of drugs, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, also called gliflozins. In addition to exerting powerful effects in reducing blood glucose, gliflozins have strong anti-neuro-inflammatory characteristics that function by inhibiting oxidative stress and cell death in the nervous system in diabetic subjects. This review presents the molecular pathways involved in diabetes-induced neurodegeneration and evaluates the clinical and laboratory studies investigating the neuroprotective effects of gliflozins against diabetes-induced neurodegeneration, with discussion about the contributing roles of diverse molecular pathways, such as mitochondrial dysfunction, oxidative stress, neuro-inflammation, and cell death. Several databases-including Web of Science, Scopus, PubMed, Google Scholar, and various publishers, such as Springer, Wiley, and Elsevier-were searched for keywords regarding the neuroprotective effects of gliflozins against diabetes-triggered neurodegenerative events. Additionally, anti-neuro-inflammatory, anti-oxidative stress, and anti-cell death keywords were applied to evaluate potential neuronal protection mechanisms of gliflozins in diabetes subjects. The search period considered valid peer-reviewed studies published from January 2000 to July 2023. The current body of literature suggests that gliflozins can exert neuroprotective effects against diabetes-induced neurodegenerative events and neuronal dysfunction, and these effects are mediated via activation of mitochondrial function and prevention of cell death processes, oxidative stress, and inflammation in neurons affected by diabetes. Gliflozins can confer neuroprotective properties in diabetes-triggered neurodegeneration, and these effects are mediated by inhibiting oxidative stress, inflammation, and cell death.

Urinary tract infections (UTIs) are common in women; more than 50% of women will be diagnosed with a UTI in her lifetime. Many of these women will go on to develop recurrent UTI. Nevertheless, evidence-based prevention of recurrent UTI is under-utilized. Here, the authors provide detailed practical advice on UTI prevention with a thorough review of the evidence. Non-antibiotic prevention measures discussed include increased fluid intake, vaginal estrogen therapy, methenamine, and cranberry. Antibiotic prophyalxis for carefully selected patients is also discussed.

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), has shown demonstrated benefits for renal and cardiovascular outcomes in large clinical trials. However, short-term concerns regarding its impact on renal function and electrolyte balance exist. This study aimed to evaluate the short-term effects of dapagliflozin on renal function and electrolyte balance in patients newly prescribed the medication. A retrospective analysis of 246 patients who initiated dapagliflozin therapy was conducted. Serum creatinine, sodium, and potassium levels were measured at baseline (before dapagliflozin) and 5-8 days after initiation (endpoint). A Wilcoxon signed-rank test, Pearson's chi-square test, and Fischer's exact test were used for the data analysis. Glycemia and sodium levels were significantly higher at the baseline compared to the endpoint (p < 0.001). Conversely, creatinine and potassium levels were significantly higher at the endpoint than at the baseline (p < 0.001). The prevalence of hyponatremia and hyperkalemia were increased at the endpoint (17.5% vs. 10.2% and 16.7% vs. 8.9%, respectively). Although not statistically significant, a trend towards increased hyponatremia with the co-administration of furosemide was observed (p = 0.089). No significant association was found between potassium-sparing medications (p > 0.05) and hyperkalemia, except for angiotensin receptor blockers (p = 0.017). The combination of dapagliflozin and furosemide significantly increased the risk of acute kidney injury (AKI) at the endpoint (p = 0.006). Age, gender, and chronic kidney disease status did not significantly influence the occurrence of AKI, hyponatremia, or hyperkalemia (p > 0.05). These findings emphasize the importance of the close monitoring of renal function and electrolyte balance, particularly in the early stages of dapagliflozin therapy, especially in patients receiving diuretics or renin-angiotensin-aldosterone system inhibitors.

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Multiple randomized controlled trials have extensively examined the therapeutic effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors, ushering in a transformative approach to treating individuals with type 2 diabetes mellitus (DM). Notably, emerging reports have drawn attention to the potential positive impacts of SGLT2 inhibitors in nondiabetic patients. In an effort to delve into this phenomenon, a comprehensive systematic literature review spanning PubMed (NLM), Medline (Ovid), and Cochrane Library, covering publications from 2000 to 2024 was undertaken. This systematic review encompassed twenty-six randomized control trials (RCTs) involving 35,317 participants. The findings unveiled a multifaceted role for SGLT2 inhibitors, showcasing their ability to enhance metabolic control and yield cardioprotective effects through a reduction in cardiovascular death (CVD) and hospitalization related to heart failure (HF). Additionally, a renalprotective effect was observed, evidenced by a slowdown in chronic kidney disease (CKD) progression and a decrease in albuminuria. Importantly, these benefits were coupled with an acceptable safety profile. The literature also points to various biological plausibility and underlying mechanistic pathways, offering insights into the association between SGLT2 inhibitors and these positive outcomes in nondiabetic individuals. Current research trends indicate a continual exploration of additional role for SGLT2 inhibitors in. Nevertheless, further research is imperative to fully elucidate the mechanisms and long-term outcomes associated with the nondiabetic use of SGLT2 inhibitors.

Patients with type 2 diabetes mellitus (T2DM) are at higher risk for urinary tract infections (UTIs), which greatly impacts their quality of life. Developing a risk prediction model to identify high-risk patients for UTIs in those with T2DM and assisting clinical decision-making can help reduce the incidence of UTIs in T2DM patients. To construct the predictive model, potential relevant variables were first selected from the reference literature, and then data was extracted from the Hospital Information System (HIS) of the Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital for analysis. The data set was split into a training set and a test set in an 8:2 ratio. To handle the data and establish risk warning models, four imputation methods, four balancing methods, three feature screening methods, and eighteen machine learning algorithms were employed. A 10-fold cross-validation technique was applied to internally validate the training set, while the bootstrap method was used for external validation in the test set. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the performance of the models. The contributions of features were interpreted using the SHapley Additive ExPlanation (SHAP) approach. And a web-based prediction platform for UTIs in T2DM was constructed by Flask framework. Finally, 106 variables were identified for analysis from a total of 119 literature sources, and 1340 patients were included in the study. After comprehensive data preprocessing, a total of 48 datasets were generated, and 864 risk warning models were constructed based on various balancing methods, feature selection techniques, and a range of machine learning algorithms. The receiver operating characteristic (ROC) curves were used to assess the performances of these models, and the best model achieved an impressive AUC of 0.9789 upon external validation. Notably, the most critical factors contributing to UTIs in T2DM patients were found to be UTIs-related inflammatory markers, medication use, mainly SGLT2 inhibitors, severity of comorbidities, blood routine indicators, as well as other factors such as length of hospital stay and estimated glomerular filtration rate (eGFR). Furthermore, the SHAP method was utilized to interpret the contribution of each feature to the model. And based on the optimal predictive model a user-friendly prediction platform for UTIs in T2DM was built to assist clinicians in making clinical decisions. The machine learning model-based prediction system developed in this study exhibited favorable predictive ability and promising clinical utility. The web-based prediction platform, combined with the professional judgment of clinicians, can assist to make better clinical decisions.

Patients with diabetes are at higher risk of cognitive impairment and memory loss than the normal population. Thus, using hypoglycemic agents to improve brain function is important for diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a class of therapeutic agents used in the management of diabetes that has some pharmacologic effects enabling them to fight against the onset and progress of memory deficits. Although the exact mediating pathways are not well understood, emerging evidence suggests that SGLT2 inhibition is associated with improved brain function. This study reviewed the possible mechanisms and provided evidence suggesting SGLT2 inhibitors could ameliorate cognitive deficits.

As heart failure (HF) progresses, ATP levels in myocardial cells decrease, and myocardial contractility also decreases. Inotropic drugs improve myocardial contractility but increase ATP consumption, leading to poor prognosis. Kyoto University Substance 121 (KUS121) is known to selectively inhibit the ATPase activity of valosin-containing protein, maintain cellular ATP levels, and manifest cytoprotective effects in several pathological conditions. The aim of this study is to determine the therapeutic effect of KUS121 on HF models.

Cultured cell, mouse, and canine models of HF were used to examine the therapeutic effects of KUS121. The mechanism of action of KUS121 was also examined. Administration of KUS121 to a transverse aortic constriction (TAC)-induced mouse model of HF rapidly improved the left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. In a canine model of high frequency-paced HF, administration of KUS121 also improved left ventricular contractility and decreased left ventricular end-diastolic pressure without increasing the heart rate. Long-term administration of KUS121 to a TAC-induced mouse model of HF suppressed cardiac hypertrophy and fibrosis. In H9C2 cells, KUS121 reduced ER stress. Finally, in experiments using primary cultured cardiomyocytes, KUS121 improved contractility and diastolic capacity without changing peak Ca2+ levels or contraction time. These effects were not accompanied by an increase in cyclic adenosine monophosphate or phosphorylation of phospholamban and ryanodine receptors.

KUS121 ameliorated HF by a mechanism totally different from that of conventional catecholamines. We propose that KUS121 is a promising new option for the treatment of HF.

According to the preclinical data, sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) may exert anticancer effects. Here, we clarified the cancer-specific mortality (primary outcome) and all-cause mortality (secondary outcome) of SGLT2is and their dose-dependency in patients with cancer undergoing standard curative treatments.

We analyzed data from patients with type 2 diabetes mellitus (T2DM) diagnosed with cancer between January 1, 2016, and December 31, 2018, enrolled from the Taiwan Cancer Registry database. Kaplan-Meier method was used to estimate all-cause mortality and cancer-specific mortality, comparing survival curves between SGLT2i users and nonusers using the stratified log-rank test. Cox proportional hazards regression was conducted to identify independent predictors for all-cause and cancer-specific mortality among the covariates.

We performed 1:2 propensity score matching of our data, which yielded a final cohort of 50,133 patients with cancer; of them, 16,711 and 33,422 were in the SGLT2i user and nonuser groups, respectively. The adjusted hazard ratio (aHR) for cancer-specific and all-cause mortality in SGLT2i users compared with nonusers was 0.21 (95 % confidence interval [CI]: 0.20-0.22) and 0.22 (95 % CI: 0.21-0.23). We divided the patients into four subgroups stratified by quartiles (Q) of cumulative defined daily doses per year (cDDDs), and all-cause and cancer-specific mortality was noted to significantly decrease with increases in dosage (from Q1 to Q4 cDDDs) in SGLT2i users compared with in nonusers (P < 0.001).

SGLT2is increase overall survival and cancer-specific survival in patients with cancer in a dose-dependent manner.

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials independent of glycemic control. The mechanisms of this cardioprotective property remain uncertain. Evidence suggests positive hemodynamic changes and favorable cardiac remodeling contributing to the clinical outcomes but results were conflicting. We aim to investigate the potential impact on hemodynamic parameters, cardiac structure and functions. This prospective observational study included T2DM patients receiving canagliflozin 100 mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by echocardiographic measurements and impedance cardiography (ICG) to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. A total of 47 patients (25 males and 22 females) averaging 64.6 ± 10.9 years had a significant reduction in HbA1c, body weight, and systolic blood pressure. Hematocrit increased significantly, while NT-proBNP remained unchanged. E/e', left atrium (LA) volume, and LA stiffness were reduced, while left ventricle (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. ICG suggested significant improvement in hemodynamic parameters with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes in large clinical trials.

To investigate how sodium-glucose co-transporter 2 inhibitors (SGLT2is) add-on therapy for metformin affects diabetic retinopathy (DR) progression in patients with type 2 diabetes mellitus (T2DM). This nationwide population-based study conducted from January 1, 2016, to December 31, 2018 involved 3,432,911 adults with T2DM in Taiwan. To adjust for potential confounders, data on sex, age, income, comorbidities, diabetes complication severity index score, staging of kidney disease, anti-diabetic medications, and index year were included. The outcome was DR progression, determined by procedure codes or the addition of ICD-9-CM or ICD-10-CM codes to the medical records of the patients during the study. Sensitivity analyses were performed to validate the findings. The adjusted hazard ratio (aHR) of DR progression was 0.89 for the SGLT2is add-on group, relative to the control group [95% confidence interval (CI) 0.81-0.99, P = 0.026]. The Kaplan-Meier curve of the cumulative incidence rate showed that the cumulative incidence of DR progression was considerably decreased in the SGLT2is cohort (log-rank P = 0.0261). The use of SGLT2is for less than 1 year and 1-2 years were associated with a significant increase in the risk of DR progression (aHR 1.56 and 1.88, respectively); however, the risk markedly reduced if the SGLT2is regimen was used for more than 2 years (aHR 0.41, 95% Cl 0.35-0.48; P < 0.001). The serial sensitivity analysis showed consistent findings. The aHR of DR progression was 0.82 for the SGLT2is cohort relative to the non-SGLT2is cohort based on the fundoscopy or indirect ophthalmoscopy findings within 1 year before the outcome date (95% Cl 0.71-0.95; P = 0.009). Co-administration of metformin and SGLT2is may reduce the risk of DR progression. Short-term use of SGLT2is may markedly increase the risk of DR, whereas prolonged use SGLT2is may significantly decrease it.

Nano-drug delivery is a rapidly growing approach in medicine that helps design and develop newer forms of drugs with more efficacy and lower adverse effects. Sodium-glucose cotransporter-2 inhibitors are an emerging class of antidiabetic agents that reduce the blood glucose levels by damping glucose reabsorption in renal proximal tubules.

This mechanism might be followed by some adverse effects that could be prevented by nano-drug delivery. Although we have still limited evidence about nanoforms of sodium-glucose cotransporter-2 inhibitors, current knowledge strongly suggests that nanotechnology can help us design more effective drugs with lower side effects. In recent years, several studies have explored the possible benefits of nanoforms of sodium-glucose cotransporter-2 inhibitors. However, clinical trials are yet to be conducted.

In the current review, we present the latest findings on the development and benefits of nanoforms of sodium-glucose cotransporter-2 inhibitors.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are part of the treatment for hyperglycemia in patients with diabetes. These drugs have shown important benefits including cardiovascular and renal protection among people with diabetes.

We report a case of a 60-year-old woman with diabetes who presented to the emergency department complaining of left flank pain radiating to the groin. The patient was on multiple antidiabetic medications, including a recently added empagliflozin, considering the difficulty in controlling hyperglycemia. She quickly developed severe sepsis with shock, and imaging studies of the abdomen revealed the presence of encapsulated gas in the left kidney compatible with emphysematous pyelonephritis (EPN). There was no presence of nephrolithiasis or other anatomical or structural abnormality that could have precipitated this focal renal infection.Besides antimicrobials, fluid resuscitation, and vasopressor agents, an emergent surgical nephrectomy, as well as intensive care, was required until the patient fully recovered. Escherichia coli was isolated from the initial blood cultures, and ceftriaxone was administered. The patient was subsequently discharged home in stable condition. Two months later, the patient was readmitted with near-syncope and abdominal pain, which was found to be related to small bowel obstruction. The patient decompensated rapidly and had a cardiac arrest even before surgical evaluation. She was resuscitated and admitted to the intensive care unit but showed no signs of neurologic recovery after the anoxic event. She did not survive this hospitalization.

The exposure of SGLT2 inhibitors in this patient seemed to have been the precipitating factor for development of complicated pyelonephritis with gas gangrene. EPN is a consequence of a severe renal parenchymal infection, which carries high mortality even with prompt treatment.

Use of SGLT2 inhibitors has expanded worldwide as there are clear clinical benefits, but we need to recognize their uncommon yet potentially fatal complications, such as EPN.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have the potential to alter the natural history of chronic kidney disease (CKD), and they should be included in cost-effectiveness analyses of screening for CKD.

To determine the cost-effectiveness of adding population-wide screening for CKD.

Markov cohort model.

NHANES (National Health and Nutrition Examination Survey), U.S. Centers for Medicare & Medicaid Services data, cohort studies, and randomized clinical trials, including the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial.

Adults.

Lifetime.

Health care sector.

Screening for albuminuria with and without adding SGLT2 inhibitors to the current standard of care for CKD.

Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), all discounted at 3% annually.

One-time CKD screening at age 55 years had an ICER of $86 300 per QALY gained by increasing costs from $249 800 to $259 000 and increasing QALYs from 12.61 to 12.72; this was accompanied by a decrease in the incidence of kidney failure requiring dialysis or kidney transplant of 0.29 percentage points and an increase in life expectancy from 17.29 to 17.45 years. Other options were also cost-effective. During ages 35 to 75 years, screening once prevented dialysis or transplant in 398 000 people and screening every 10 years until age 75 years cost less than $100 000 per QALY gained.

When SGLT2 inhibitors were 30% less effective, screening every 10 years during ages 35 to 75 years cost between $145 400 and $182 600 per QALY gained, and price reductions would be required for screening to be cost-effective.

The efficacy of SGLT2 inhibitors was derived from a single randomized controlled trial.

Screening adults for albuminuria to identify CKD could be cost-effective in the United States.

Agency for Healthcare Research and Quality, Veterans Affairs Office of Academic Affiliations, and National Institute of Diabetes and Digestive and Kidney Diseases.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications, owing to their positive cardiovascular and renal effects. SGLT2 inhibitors reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reductions in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data on SGLT2 inhibitors in special populations, including patients with acute myocardial infarction, acute HF, right ventricular (RV) failure, left ventricular assist device (LVAD), and type 1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these medications.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to improve cardiovascular and renal outcomes in patients with established cardiovascular disease, chronic kidney disease (CKD), and heart failure (HF) with reduced or preserved ejection fraction. Clinical benefit has been substantiated in patients with and without type 2 diabetes (T2D). Consequently, SGLT2is have an increasingly important role in HF and CKD management that extends beyond T2D treatment. Their pleiotropic pharmacological effects underlying their cardiovascular and renal benefits are not completely understood but include significant effects beyond blood glucose reduction. SGLT2is inhibit the reabsorption of glucose and sodium in the proximal tubule which, in addition to lowering blood glucose, activates tubuloglomerular feedback, leading to reduced glomerular hydrostatic pressure and the mitigation of glomerular filtration rate loss. SGLT2is have diuretic and natriuretic effects, leading to decreased blood pressure, preload, and left ventricular (LV) filling pressure, and improvements in other surrogates of afterload. In HF, SGLT2is mitigate the risks of hyperkalemia and ventricular arrhythmia and improve LV dysfunction. SGLT2is also reduce sympathetic tone and uric acid levels, increase hemoglobin levels, and are postulated to have anti-inflammatory properties. This narrative review discusses the multifactorial and interrelated pharmacological mechanisms underlying the cardiovascular and renal benefits of SGLT2is.

Clinical practice guidelines are helpful for clinicians, and their proper implementation could improve the quality of care and management of participants with diabetes. This study aimed to evaluate the degree of adherence to the Clinical Practice Guidelines (CPG) recommendations among obese, frail, or recently diagnosed type 2 diabetes mellitus (T2DM) participants in primary care centers in Spain.

We perform a cross-sectional study on a national level in two phases. In the first phase, study participants were recruited, and their clinical data were collected. In the second phase, data related to the participating physicians were collected.

In total, 882 participants from 240 physicians were analyzed. According to the study questionnaire, most participants from all three clinical groups had adequate adherence to the CPG. This percentage was highest among the recently diagnosed T2DM (91.6%) and lowest percent of frail T2DM persons (74.7%). The inadequate adherence to the guidelines was observed mainly among the obese and frail participants with T2DM from medical doctors with low CPG knowledge (3.4% and 3.5%, respectively). Regarding the patient's characteristics and degree of adherence to the guidelines, the participants with inadequate adherence were generally older, with higher BMI, poorer HbA1c control, and fewer visits with primary care physicians. Most (57%) primary care physicians had moderate CPG knowledge. In our multivariable logistic model, we did not observe statistically significant odds ratios for different characteristics related to the physicians/consultation and low CPG knowledge.

The results of our cross-sectional study observe adequate adherence to the clinical guidelines by the primary care physicians for the majority of the participants with obesity, frailty, or newly diagnosed with T2DM.

Epicardial adipose tissue is a layer of adipocytes that physiologically surround the myocardium and play some physiologic roles in normal heart function. However, in pathologic conditions, the epicardial adipose tissue can present a potent cardiac risk factor that is capable of impairing heart function through several pathways, increasing the risk of dysrhythmia and creating an inflammatory milieu around the heart tissues. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a relatively newly introduced class of antidiabetes drugs which effectively normalize blood glucose via overt glycosuria. Some recent reports suggest that these drugs are able to modulate epicardial adiposity and decrease the risk of cardiac complications in diabetic patients who are at higher risk of epicardial adiposity-dependent cardiac disorders. If proven to be true, these antidiabetic drugs can provide dual benefits as both hypoglycemic agents and as epicardial adiposity normalizing agents, thus providing cardiac benefits. In this study, we discuss the physiological and pathophysiological importance of epicardial adiposity and the potential positive effects of SGLT2is in the diabetic milieu.

Cardiac rehabilitation (CR) has evolved over time not only to improve cardiorespiratory fitness through exercise but also to promote lifestyle-related behaviors to manage cardiovascular disease risk factors. Given the prevalence of obesity, diabetes mellitus, metabolic syndrome, and heart failure, CR serves as an ideal setting to monitor and, when indicated, intervene to ensure that individuals are optimally treated.

The objective of this report was to review current antihyperglycemic agents and discuss the role for these medications in the care and treatment of individuals participating in CR.

There is strong evidence that the benefits provided by some antihyperglycemic medications go beyond glycemic control to include general cardiovascular disease risk reduction. Health care professionals in CR should be aware of the cardiovascular benefits of newer antihyperglycemic agents, as well as the treatment approach to patients with type 2 diabetes, obesity, and heart failure.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a newly developed class of highly effective antidiabetic therapies that normalize hyperglycemia via urinary glucose excretion. However, they may be accompanied by certain side effects that negatively impact their therapeutic benefits. SGLT2is induce a metabolic shift from glucose to fatty acids and thus increase lipolysis which, in turn, induces ketogenesis. The complete pathways linking SGLT2is to ketoacidosis have not yet been fully elucidated, though much is now known. Therefore, in this mechanistic study, we present the current knowledge and shed light upon the possible cellular pathways involved. A deeper understanding of the possible links between SGLT2is and ketogenesis could help to prevent adverse side effects in diabetic patients treated with these drugs.

Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D.

Chronic hyperglycemia induces pathophysiologic pathways with negative effects on the metabolism of most substrates as well as lipids and lipoproteins, and thereby induces dyslipidemia. Thus, the diabetic milieu is commonly accompanied by different levels of atherogenic dyslipidemia, which is per se a major risk factor for subsequent complications such as atherosclerosis, coronary heart disease, acute myocardial infarction, ischemic stroke, and nephropathy. Therefore, readjusting lipid metabolism in the diabetic milieu is a major goal for preventing dyslipidemia-induced complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of relatively newly introduced antidiabetes drugs (including empagliflozin, canagliflozin, dapagliflozin, etc.) with potent hypoglycemic effects and can reduce blood glucose by inducing glycosuria. However, recent evidence suggests that they could also provide extra-glycemic benefits in lipid metabolism. It seems that they can increase fat burning and lipolysis, normalizing the lipid metabolism and preventing or improving dyslipidemia. Nevertheless, the exact mechanisms involved in this process are not well-understood. In this review, we tried to explain how these drugs could regulate lipid homeostasis and we presented the possible involved cellular pathways supported by clinical evidence.

Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that was recently approved in the USA and the EU for the treatment of adults with chronic kidney disease (CKD) with or without diabetes mellitus (DM). The DAPA-CKD trial showed a 39% decline in the risk of worsening kidney function, onset of end-stage kidney disease, or kidney failure-related death. Patients with lower levels of eGFR and higher levels of albuminuria are among those who stand to gain the greatest absolute benefits. These benefits were similar in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related nephrotoxicity. Suggested mechanisms for renal protection include hemodynamic effects; BP reduction and improving salt sensitivities and metabolic effects; and glucose, uric acid and triglycerides (TG)-lowering effects. There have been already many excellent reviews on dapagliflozin and CKD management. Most of them cover both efficacy and safety. This review will focus on clinical perspectives and patient selection for the practicing clinician.

Sodium-glucose co-transporter-2 inhibitors (SGLT2-I's) are novel oral hypoglycaemic agents, with proven decreased MACE and re-hospitalisation risk in type 2 diabetic patients with concomitant heart failure. This study aimed to assess the current practice in the use of SGLT2-I's in general medical units at a large metropolitan health service.

A retrospective audit was conducted of patients admitted to general medicine over a 12 month period (between April 2018 and 2019). Inclusion criteria included decompensated heart failure of any aetiology and ejection fraction, and type 2 diabetes mellitus with an HbA1c ⩾ 7 within 6 months of the admission period. A total of 150 admissions fulfilled criteria. Baseline demographics and comorbidities identified an older, more comorbid population than reference trials. These included age (75% over 75 years), smoking history (46%), hypertension (83%), chronic kidney disease grade IV or V (26%), previous myocardial infarction (57%), stroke (18%), atrial fibrillation (55%) and known left ventricular ejection fraction < 50% (38%). Co-prescribed medications included ACE-I/ARB (53%), beta-blocker (67%), loop diuretic (87%), thiazide (7%), MRA (31%), insulin (57%), metformin (47%), sulphonylurea (31%), DPP-4 Inhibitor (21%), GLP-1 analogue (6%) and 15% of patients had an HbA1c > 10. There was a significant difference between patients in our study eligible for and prescribed metformin (66/111) compared to SGLT-2 inhibitors (4/25) (P = .013). A total of 26 patients had readmissions within 28 days, of which one had been discharged on an SGLT2-I.

The results of this study identified significant under prescribing of SGLT2-I's in eligible type 2 diabetic patients with heart failure admitted under general medicine.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an insulin-independent class of oral antihyperglycemic medication and from recently established therapy in chronic heart failure patients. A rare, but potentially life-threatening complication of SGLT2 inhibitor use is euglycemic diabetic ketoacidosis. We described a case of a middle-aged male patient with type 2 diabetes who developed metabolic ketoacidosis after a few days of empagliflozin administration. SGLT2 inhibitor related ketoacidosis presents with euglycemia or only modestly elevated glucose blood concentrations, which causes delayed detection and treatment of ketoacidosis. There are multiple possible risk factors and mechanism that might contribute to the pathogenesis of ketoacidosis. It is implied that SGLT2 inhibitor use and prescription by non-diabetologists (cardiologists, nephrologists, family physicians, etc.) will continue to grow in the future. It is important to inform the general cardiac public about this rare but serious side effect of SGLT2 inhibitors.

Many patients with diabetes mellitus, especially those with chronic kidney disorders, have some degree of anemia due to a spectrum of causes and underlying pathophysiologic pathways. As such, enhancement in erythropoiesis is important in these patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of antidiabetic drugs with confirmed protective effects in kidney and cardiovascular tissues. Recent evidence suggests that these drugs may provide additional benefits in enhancing hematopoietic processes in diabetic patients. Though the exact mediating pathways have not been fully elucidated, cellular mechanisms are likely involved. In the current study, we present the potential pathways by which SGLT2i may modulate hematopoiesis and stimulate erythropoiesis.

The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration.