Sex differences in the risk of metformin-associated gastrointestinal adverse events: A systematic review and meta-analysis
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.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,968 participants or records.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.