A study of over 40,000 patients with type 2 diabetes has found that treatment with metformin reduced the risk of new-onset osteoarthritis (OA) by 24% compared to treatment with a sulfonylurea. Metformin also reduced the incidence of joint replacement, although this difference was statistically non-significant. These findings are published in JAMA Network Open.¹

In this retrospective study, researchers investigated the risk of incident osteoarthritis and joint (knee or hip) replacement in patients aged 40 years or older with type 2 diabetes on metformin. Data for the present study was obtained from the Clinformatics Data Mart Database from December 2003 to December 2019. The selected patients had been registered with the database continually for at least one year. Patients who had type 1 diabetes, or had been already diagnosed with OA, inflammatory arthritis or had undergone joint replacement were not included in the study. Type 2 diabetes patients being treated with a sulfonylurea were included in the study as a control group. Each group included 20,937 participants. The mean age of the participants was 62 years; nearly 60% of them were males.

Adjusted analysis revealed that treatment with metformin was associated with 24% lower risk of developing new-onset OA compared to those treated with a sulfonylurea with adjusted hazard ratio (aHR) of 0.76. However, no statistically significant between-group difference was noted in the risk of joint replacement (aHR 0.80). The incidence rate of joint replacement in the metformin group was 1.5 events per 1,000 person-years in comparison to 2.1 events per 1,000 person-years in the sulfonylurea group.

A sensitivity analysis was done to further validate the strength of the association with 8277 patients each, who were only ever treated with either metformin or a sulfonylurea. Similar trends were observed. The reduced risk for OA with metformin (vs a sulfonylurea) was found to persist (aHR 0.77) with a 23% reduction in the risk of incident OA and the risk of joint replacement did not acquire statistical significance (aHR 1.04).

Patients treated with a sulfonylurea who had been earlier treated with metformin were also analysed. Their risk of developing OA was similar to those currently being treated with metformin (aHR 0.92). But when compared with patients treated with a sulfonylurea but never with metformin, the current metformin-treated patients had a significantly lower risk of OA (aHR 0.71).

Metformin has been the mainstay of type 2 diabetes treatment for decades. The easy accessibility and affordability have further propagated its use as the first-line treatment option. Metformin is a pleiotropic drug and has beneficial effects beyond diabetes such as anti-inflammatory, immunomodulatory, antioxidant, anticancer, antiaging and anti-atherosclerotic. It also helps in weight loss.

This study provides evidence supporting the protective effect of metformin against development of osteoarthritis. However, “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,” write the authors. They also note a lack of data for physical activity or history of trauma to the affected joint/s as a limitation of their study and suggest further studies to investigate the role of metformin in the treatment or prevention of OA.

Reference

1. Baker MC, et al. Development of osteoarthritis in adults with type 2 diabetes treated with metformin vs a sulfonylurea. JAMA Netw Open. 2023 Mar 1;6(3):e233646. doi: 10.1001/jamanetworkopen.2023.3646.