Metformin Could Lower Osteoarthritis Risk in Type 2 Diabetes

An analysis of real-world data from more than 40,000 individuals with type 2 diabetes suggests use of metformin could aid in lowering the risk of osteoarthritis and need for joint replacements.¹

A retrospective cohort study leveraging data propensity-matched data, results of the study indicate risk of developing osteoarthritis was reduced by 24% with metformin use relative to sulfonylureas, with further analysis indicated a nonsignificant 20% reduction in risk of joint replacement.¹

“In our large, nationwide cohort study of individuals with diabetes, metformin treatment was associated with a significant reduction in the risk of developing [osteoarthritis] compared with sulfonylurea treatment. Results from this study must be interpreted with caution due to the lack of data on body mass index, and the possibility that weight loss induced by metformin may have accounted for some of the benefit seen,” wrote investigators.¹

A cornerstone of diabetes management for decades, research into the effects of metformin has been the subject of a multitude of expansive studies, trials, and reviews since approval in 1994.² With osteoarthritis and joint replacement posing a significant threat to the quality of life of an aging population of T2D, a team of investigators led by Matthew C. Baker, MD, MS, of the Division of Immunology and Rheumatology at Stanford University, conducted the current study to better understand these potential associations based on previous research indicating metformin may have a protective association against osteoarthritis.¹

With this in mind, investigators designed their retrospective cohort study using claims data from the Clinformatics Data Mart database for a time period lasting from December 2003-December 2019. Using time-conditional propensity score matching and limiting their study individuals aged 40 years or older with T2D and at least 1 year of continuous enrollment, investigators identified 20,937 individuals for inclusion in the metformin and reference group. For the purpose of analysis, the reference group was comprised of people with T2D using sulfonylureas.¹

This cohort had a mean age of 62.0 (SD, 11.5) years, 58.2% were males, and the mean Charlson comorbidity score was 0.71 (SD, 1.35). In the metformin group, the mean duration of treatment was 12.34 (SD, 10.70) months and, in the sulfonylurea group, the mean duration of treatment was 12.56 (SD, 12.37) months.¹

The primary outcomes of interest for the study were incident osteoarthritis and joint replacement. Investigators used Cox proportional hazards models to estimate risk of each primary outcome. Investigators also planned a sensitivity analysis among subgroups of patients who were only ever treated with metformin and only ever treated with a sulfonylurea.¹

Upon analysis, results indicated use of metformin was associated with a reduced risk of developing osteoarthritis relative to use of a sulfonylurea (adjusted hazard ratio [aHR], 0.76 [95% confidence interval [CI], 0.68-0.85]; P <.001). However, there difference in risk of joint replacement failed to reach statistical significance (aHR, 0.80 [95% CI, 0.50-1.27]; P=.34).¹

In their sensitivity analysis, which included 8277 people in each group, investigators found the observed trend of reduced risk for developing osteoarthritis persisted among those treated with metformin compared with a sulfonylurea (aHR, 0.77 [95% CI, 0.65-0.90]; P <.001) and the risk of joint replacement remained not statistically significant (aHR, 1.04 [95% CI, 0.60-1.82]; P=.89).¹

“This study further supports the preclinical and observational data that show metformin may have a protective association against the development of [osteoarthritis]. Future interventional studies with metformin for the treatment or prevention of [osteoarthritis] should be considered,” investigators added.¹

References

1. Baker MC, Sheth K, Liu Y, et al. Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. JAMA Netw Open. 2023;6(3):e233646. doi:10.1001/jamanetworkopen.2023.3646
2. Corcoran C, Jacobs TF. Metformin. [Updated 2022 May 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK518983/