NEW evidence suggests that metformin, a cornerstone therapy for Type 2 diabetes, may also have therapeutic potential in osteoarthritis (OA), extending its relevance beyond glycaemic control.
Traditionally prescribed to improve glycaemic control, metformin is now attracting attention for its anti-inflammatory and metabolic effects beyond diabetes. Two recent studies, one a randomized controlled trial and the other a long-term population-based cohort analysis, point towards a possible role for metformin in both symptom relief and disease risk reduction in OA.
Diabetes Drug Reduces Knee Pain in OA
In a double-blind randomised trial published in July 2024, researchers investigated metformin in people with symptomatic knee osteoarthritis and overweight or obesity. A total of 107 participants were randomised to receive either oral metformin at 2000 mg per day or placebo for 6 months.
Participants treated with metformin experienced a significantly greater reduction in knee pain compared with placebo, measured using a 100-mm visual analogue scale. Mean pain scores fell by 31.3 mm in the metformin group versus 18.9 mm in the placebo group, resulting in a statistically significant between-group difference of −11.4 mm. Although this improvement fell just short of the predefined minimum clinically important difference, the effect size was moderate, suggesting meaningful benefit for a subset of patients.
Importantly, metformin was generally well tolerated, with gastrointestinal symptoms such as diarrhea and abdominal discomfort being the most commonly reported adverse events.
Lower Long-Term Risk of Osteoarthritis
Supporting these findings, a large Swedish twin study examined whether metformin exposure influenced the long-term risk of developing OA. Over an 11-year follow-up, individuals who initiated metformin had a lower risk of receiving an OA diagnosis compared with their non-treated co-twins, even after adjusting for age, sex, body mass index, smoking, and education.
After adjustment, metformin use was associated with a 40% reduction in relative OA risk. At 10 years, the cumulative incidence of OA was approximately 3 percentage points lower among metformin users, suggesting a potential protective effect on joint health.
A Case for Cross-Specialty Collaboration
Taken together, these findings highlight the potential for a diabetes drug to influence musculoskeletal disease, reinforcing the need for closer collaboration between endocrinology and rheumatology. Metabolic dysfunction and low-grade inflammation are increasingly recognised as contributors to OA pathogenesis, particularly in people with overweight or obesity, providing a plausible biological rationale for metformin’s effects.
While larger randomised trials are needed before metformin can be recommended routinely for OA, the emerging evidence opens the door to drug repurposing strategies that bridge chronic disease silos. For clinicians managing patients at the intersection of diabetes, obesity, and osteoarthritis, metformin may one day offer benefits that extend well beyond glucose control.
References
Pan F et al. Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial. JAMA. 2025;333(20):1804-12.
Magnusson K et al. Metformin and incident osteoarthritis: Causal insights from a co-twin control study. Osteoarthritis and Cartilage. 2025;DOI: 10.1016/j.joca.2025.12.014.
