Qu Biao, Li Zheng, Hu Wei
Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China.
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.
World J Diabetes. 2025 Apr 15;16(4):100533. doi: 10.4239/wjd.v16.i4.100533.
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.
糖尿病由于其高患病率和严重并发症，对全球健康构成了重大威胁。高血糖状态会损害血管内皮细胞并扰乱脂质代谢，从而促进血管疾病尤其是动脉粥样硬化疾病的发展。积极的血糖控制与血管干预相结合对于预防和治疗糖尿病相关的动脉粥样硬化至关重要。建议二甲双胍应与已证实具有血管益处的降糖药物联合使用，以治疗合并动脉粥样硬化疾病的2型糖尿病（T2DM）。临床研究表明，首选的联合用药是二甲双胍与胰高血糖素样肽-1受体激动剂或钠/葡萄糖协同转运蛋白-2抑制剂，这两种联合用药可带来额外的血管益处并降低动脉粥样硬化并发症的风险。同样，二甲双胍与降脂药物的联合治疗在糖尿病和血脂异常患者的血糖控制和降脂方面也显示出相加作用，不过需要广泛的临床试验以动脉粥样硬化相关结局来支持其血管益处。此外，正如一些动物研究所示，二甲双胍与全身抗氧化或抗炎治疗联合使用也可能带来额外的血管益处。例如，最近一项研究发现，额外补充胆钙化醇和牛磺酸可增强二甲双胍控制糖尿病的疗效，同时降低相关动脉粥样硬化并发症的风险。然而，这些潜在益处仍需临床研究证据的验证。尽管存在局限性，如不同患者群体之间的异质性以及长期结局的不足，但这些努力有助于找到最佳药物组合，以改善T2DM的管理并减少其动脉粥样硬化并发症。
