Aims: Examine the efficacy of metformin compared to placebo or other glucose-lowering medications on microvascular outcomes in patients with Type 2 Diabetes Mellitus (T2DM).
Methods: 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).
Results: 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.
Conclusions: 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.
Keywords: Metformin; Microvascular; Patient important outcomes; Systematic review; Type 2 diabetes.
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