Data_Sheet_1_Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies.docx

BackgroundThe cardiovascular protection effect of metformin on patients with type 2 diabetes mellitus (T2DM) remains inconclusive. This systemic review and meta-analysis were to estimate the effect of metformin on mortality and cardiovascular events among patients with T2DM.
MethodsA search of the Pubmed and EMBASE databases up to December 2021 was performed. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method.
ResultsA total of 39 studies involving 2473009 T2DM patients were adopted. Compared to non-metformin therapy, the use of metformin was not significantly associated with a reduced risk of major adverse cardiovascular event (MACE) (HR = 1.06, 95%CI 0.91–1.22; I2 = 82%), hospitalization (HR = 0.85, 95%CI 0.64–1.13; I2 = 98%), heart failure (HR = 0.86, 95%CI 0.60–1.25; I2 = 99%), stroke (HR = 1.16, 95%CI 0.88–1.53; I2 = 84%), and risk of AMI (HR = 0.88, 95%CI 0.69–1.14; I2 = 88%) in T2DM patients. Metformin was also not associated with significantly lowered risk of MACE compared to dipeptidyl peptidase-4 inhibitor (DPP-4i) in T2DM patients (HR = 0.95, 95%CI 0.73–1.23; I2 = 84%).
ConclusionsThe effect of metformin on some cardiovascular outcomes was not significantly better than the non-metformin therapy or DPP-4i in T2DM patients based on observational studies.