Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus

Abstract

Background Metformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive. Methods We searched PubMed and Embase for data extracted from inception to July 14, 2020, with a registration in PROSPERO (CRD42020177283). This study included randomized controlled trials (RCT) assessing the cardiovascular effects of metformin for T2DM. This study is followed by PRISMA and Cochrane guideline. Risk ratio (RR) with 95% CI was pooled across trials by a random-effects model. Primary outcomes include all-cause mortality and cardiovascular mortality. Results We identified 29 studies that randomly assigned patients with 371 all-cause and 227 cardiovascular death events. Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69–1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70–1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61–1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54–1.13; P = 0.19). Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin. Conclusion The combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of all-cause/cardiovascular mortality and cardiovascular events for T2DM. However, the conclusion shall be explained cautiously considering the limitations from UK Prospective Diabetes Study (UKPDS).

Mitophagy in Diabetic Cardiomyopathy: Roles and Mechanisms

“…However, the effect of metformin on cardiovascular mortality of T2DM patients remains controversial. A recent meta-analysis suggests that compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality, cardiovascular mortality, and heart failure ( Li et al, 2021 ). Therefore, whether the mechanism of metformin improving myocardial damage through mitophagy in diabetic animal models is also applicable to T2DM patients still needs to be supported by more clinical studies.…”

Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy

“…The methodology is performed as previously described (Li et al, 2021). We systematically searched PubMed, embase, Web of Science, Cochrane Library, and several Chinese databases (CNKI, VIP, and Wanfang databases) until January 10, 2021.…”

Roles of Nursing in the Management of Geriatric Cardiovascular Diseases

“…CVD remains the main killer for people throughout the world (14,29,30). At the beginning of this manuscript, we introduce the background of CVD and nursing, followed by roles of nursing in the management of CVD such as HF and myocardial ischemia.…”