Sex differences in the risk of metformin-associated gastrointestinal adverse events: A systematic review and meta-analysis.
Alok Kumar, Antonino Catalano, Emilia Biamonte et al.
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In 30 seconds
This systematic review and meta-analysis examined whether sex is associated with metformin-related gastrointestinal adverse events (GIAEs). It included seven studies—five cohort studies, one case-control study and one randomised controlled trial—with 7,968 participants (3,106 females and 4,862 males). Females had higher pooled odds of GIAEs than males (OR 1.85, 95% CI 1.58-2.17), and sensitivity analyses showed consistent findings. The evidence combines observational studies with one trial, so the result indicates a sex-related difference in reported risk rather than establishing that sex itself causes gastrointestinal intolerance.
Key findings
- Across seven studies and 7,968 participants, females had higher odds of metformin-associated GIAEs than males (OR 1.85, 95% CI 1.58-2.17).
- Sensitivity analyses produced findings consistent with the overall result.
Why it matters
Gastrointestinal intolerance can affect metformin use, and this pooled analysis suggests that reported adverse-event risk may differ by sex. Recognising this potential difference can inform how clinicians interpret gastrointestinal symptoms and consider tolerability during metformin treatment, while the mixed study designs mean the estimate should not be treated as proof of a causal effect.
What to keep in mind
The evidence included only seven studies and combined observational studies with one randomised trial; the abstract does not report further limitations.