Qu B, Li Z, Hu W. Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases. World J Diabetes 2025; 16(4): 100533 [DOI: 10.4239/wjd.v16.i4.100533]
Corresponding Author of This Article
Wei Hu, PhD, Professor, Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, No. 678 Furong Road, Hefei 230601, Anhui Province, China. huwei@ahmu.edu.cn
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Apr 15, 2025; 16(4): 100533 Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.100533
Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases
Biao Qu, Zheng Li, Wei Hu
Biao Qu, Wei Hu, Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
Zheng Li, Jiangsu Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, College of Health Sciences, School of Life Sciences, Jiangsu Normal University, Xuzhou 221000, Jiangsu Province, China
Author contributions: Hu W designed the article; Qu B and Li Z drafted and revised the article.
Supported by the Natural Science Research Project of Anhui Province, No. 2023AH053172; National Natural Science Foundation of Anhui Province, No. 2408085QH260; Projects of Administration of Traditional Chinese Medicine of Anhui Province, No. 2024CCCX082; and National Natural Science Foundation Incubation Program of The Second Hospital of Anhui Medical University, No. 2022GMFY08.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Hu, PhD, Professor, Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, No. 678 Furong Road, Hefei 230601, Anhui Province, China. huwei@ahmu.edu.cn
Received: August 20, 2024 Revised: December 30, 2024 Accepted: January 10, 2025 Published online: April 15, 2025 Processing time: 192 Days and 19.8 Hours
Abstract
Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications. The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism, thus contributing to the development of vascular disorders, especially atherosclerotic diseases. Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis. It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes (T2DM) complicated with atherosclerotic diseases. Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor, which could offer additional vascular benefits and reduce the risk of atherosclerotic complications. Likewise, combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia, whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits. Moreover, co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies. For instance, a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications. However, these potential benefits remain need validation by the evidence from clinical studies. Despite the limitations, such as heterogeneity across different patient populations, and deficiency in long-term outcomes, such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.
Core Tip: The hyperglycemic state can actually induce atherosclerosis development or further accelerate its progression, which leads to cardio-cerebrovascular diseases associated with high morbidity and mortality. As metformin is the preferred first-line drug to manage type 2 diabetes, metformin combined with either hypoglycemic agents, hypolipidemic agents, or systemic antioxidant/anti-inflammatory agents, have been investigated to provide additional vascular benefits. It is quite clear that such exploration can contribute to finding a better drug combination to mitigate diabetes-associated atherosclerotic diseases.
