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

José Gerardo González-González, Ricardo Cesar Solis, Alejandro Díaz González-Colmenero, Karina Raygoza-Cortez, Pablo J. Moreno-Peña, Alicia L. Sánchez, Rozalina G. McCoy, Naykky Singh Ospina, Spyridoula Maraka, Juan P. Brito, René Rodriguez-Gutierrez

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Article number109821
JournalDiabetes Research and Clinical Practice
StatePublished - Apr 2022


  • Metformin
  • Microvascular
  • Patient important outcomes
  • Systematic review
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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