Metformin Reduces Osteoarthritis Risk Save

Metformin may help cut the risk of osteoarthritis (OA) in those with type 2 diabetes, researchers reported.

In a retrospective cohort study of nearly 21,000 adults with diabetes, those who were taking metformin saw a 24% lower risk for developing OA compared with those taking a sulfonylurea (adjusted hazard ratio [aHR] 0.76, 95% CI 0.68-0.85), according to Matthew Baker, MD, MS, of Stanford University in Palo Alto, California, and colleagues.

Metformin-treated patients saw an OA incidence rate of 27.5 events per 1,000 person-years vs 39.6 events per 1,000 person-years for those treated with a sulfonylurea, the group wrote in JAMA Network Open.

The models were adjusted for age, sex, race and ethnicity, geographical region, education, Charlson comorbidity score, and outpatient visit frequency.

Taking this one step further, Baker's group stratified the analysis according to patients treated with a sulfonylurea who were previously treated with metformin. Here, the risk reduction for OA was not significantly different from current metformin users (aHR 0.92, 95% CI 0.76-1.12). But these patients previously exposed to metformin still had a significantly lower OA risk than those never exposed (aHR 0.71, 95% CI 0.62-0.81).

"One possible hypothesis for this finding is that individuals in the sulfonylurea group with prior exposure to metformin derived a degree of long-lasting protection associated with the metformin exposure," the researchers explained. These findings fall in line with previous researchopens in a new tab or window that already suggested a protective OA benefit with metformin, Baker's group pointed out.

"It is possible that metformin use resulted in more weight loss than sulfonylurea use, and the reduction in OA we observed was mediated primarily by weight loss," the study authors said, but then added that they "believe metformin likely exerts protective associations beyond what can be attributed to weight loss alone."

This protective benefit didn't appear to extend to the risk of joint replacement (aHR 1.04, 95% CI 0.60-1.82). The incidence rate of joint replacement for individuals treated with metformin was 1.5 events per 1,000 person-years, compared with 2.1 events per 1,000 person-years for sulfonylurea-treated patients.

This particular finding diverges from another prior studyopens in a new tab or window that had suggested daily metformin was associated with a 30% lower risk for total knee and hip replacement compared with no metformin.

Data for the present study came from claims of patients covered with commercial or Medicare Advantage from the Optum deidentified Clinformatics Data Mart Database from 2003 to 2019. Among the 20,937 individuals included, 58% were male and the average age was 62 years. All individuals were at least age 40 with type 2 diabetes. Those with type 1 diabetes, existing OA, inflammatory arthritis, or joint replacement were excluded.

The researchers acknowledged that they included patients who switched from metformin to sulfonylureas, but not vice versa, potentially creating some bias in the findings. Another limitation to the study was an inability to account for medication adherence in either treatment group.

"Future interventional studies with metformin for the treatment or prevention of OA should be considered," suggested Baker's group.

Source Reference: Baker MC, et al "Development of osteoarthritis in adults with type 2 diabetes treated with metformin vs a sulfonylurea" JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2023.3646.