Metformin and incident osteoarthritis: Causal insights from a co-twin control study
Karin Magnusson1, Aleksandra Turkiewicz2, Andrea Dell'Isola2
1Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Remissgatan 4, Lund 222 42, Sweden; Norwegian Institute of Public Health, Cluster for Health Services Research, Sandakerveien 24C, Oslo 0473, Norway.
Osteoarthritis and Cartilage
|December 20, 2025
Summary
Metformin treatment may reduce the risk of osteoarthritis (OA) diagnosis. This study found a lower incidence of OA in individuals taking metformin compared to their non-treated twins over 11 years.
Area of Science:
- Endocrinology
- Rheumatology
- Epidemiology
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease.
- Metformin is a common medication for type 2 diabetes.
- The potential impact of metformin on OA risk is not well-established.
Purpose of the Study:
- To investigate the association between initiating metformin treatment and the risk of incident osteoarthritis (OA) diagnosis.
- To compare OA risk in metformin users versus non-users within a co-twin control framework.
- To assess OA risk over an 11-year follow-up period.
Main Methods:
- A co-twin control study design was employed, including discordant twin pairs and singletons.
- Data from 52,341 individuals aged 35-75 in Sweden were analyzed.
- Stratified Cox models and Weibull shared frailty models were used, adjusting for BMI, smoking, age, sex, and education.
Main Results:
- Metformin initiators showed a reduced risk of OA diagnosis (adjusted HR=0.60; 95% CI=0.44-0.82).
- The 10-year cumulative incidence of OA was approximately 3 percentage points lower in metformin users (6.7%) compared to non-users (9.7%).
- Treated twins had a higher baseline body mass index (BMI).
Conclusions:
- Initiating metformin treatment may be associated with a decreased risk of incident osteoarthritis diagnosis in specialist care.
- The findings suggest a potential protective effect of metformin against OA development.
- Further research is warranted to confirm these findings and explore underlying mechanisms.
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