Sex differences in the risk of metformin-associated gastrointestinal adverse events: A systematic review and meta-analysis
In brief
Women taking metformin face nearly twice the risk of GI side effects as men
A meta-analysis of seven studies involving almost 8,000 patients found that females had about 85% higher odds of metformin-related gastrointestinal adverse events compared with males. The finding was consistent across cohorts, a case-control and a trial, suggesting clinicians should watch women more closely for intolerance, though the analysis cannot prove causality.
- Journal
- Diabetes research and clinical practice (Q1)
- Published
- 6 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Alok Kumar, Antonino Catalano, Emilia Biamonte, Basilio Pintaudi, Pentti Nieminen, Sunita Singh
- PMID
- 42702238
- DOI
- 10.1016/j.diabres.2026.113560
Why clinicians should know about it
- Picked for Internal Medicine (top studies of the week, 13 September 2026): Sex differences in metformin GI adverse events
- Picked for Epidemiology (top studies of the week, 13 September 2026): Systematic review/meta‑analysis of sex differences in metformin GIAEs
Abstract
Evidence regarding sex-related differences in metformin-associated gastrointestinal adverse events (GIAEs) remains limited. This systematic review and meta-analysis aimed to determine whether sex influences the risk of metformin-associated GIAEs. We included observational studies (5 cohorts and 1 case-control) and a randomized controlled trial identified through searches of Ovid MEDLINE, Ovid EMBASE, and CENTRAL from inception to June 2026. Eligible studies reported metformin-associated GIAEs separately in females and males, while studies in which GIAEs could not be attributed to metformin were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for randomized trials. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects meta-analysis. Seven studies (five cohort studies, one case-control study, and one randomized controlled trial) involving 7,968 participants (3,106 females and 4,862 males) were included. Females had significantly higher odds of metformin-associated GIAEs than males (OR 1.85, 95% CI 1.58-2.17), with consistent findings in sensitivity analyses. Females may have a higher risk of metformin-associated GIAEs than males, highlighting the importance of considering sex differences when prescribing metformin and monitoring gastrointestinal intolerance.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.