Effect of metformin on microvascular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis

Examine the efficacy of metformin compared to placebo or other glucose-lowering medications on microvascular outcomes in patients with Type 2 Diabetes Mellitus (T2DM).

MEDLINE, EMBASE, Web of Science, and Scopus were searched from database inception to March 2020. We included randomized clinical trials of patients with T2DM receiving metformin compared with another active glucose-lowering treatment or placebo in which a microvascular outcome was assessed. The risk of bias was assessed using the Cochrane Risk of Bias tool. Microvascular complications included kidney-related outcomes, retinopathy, and peripheral neuropathy. An inverse-weighted variance random-effect meta-analysis was performed to estimate drugs effect over microvascular disease. PROSPERO (CRD42019120365).

Nineteen RCTs (n = 18,181) were included. Metformin increased estimated glomerular filtration rate (eGFR) by a mean difference (MD) of 1.08 (95% CI 0.84 to 1.33 ml/min/1.73 m²) after 24 weeks. No effect was found on urinary albumin-creatinine ratio, serum creatinine, and end-stage kidney disease; Patient-important outcomes regarding kidney disease, retinal outcomes, peripheral neuropathy or quality of life were not assessed by any of the included studies and could not be analyzed.

There is no evidence of clinically significant beneficial effect of metformin therapy as compared to other glucose-lowering medications or placebo on the examined microvascular complications.