When examining metformin use, researchers from China, Taiwan, and Australia discovered a reduced risk of total knee replacement (TKR) and total hip replacement (THR). This scientific journey began as an effort to build stronger evidence of an association between the use of metformin and joint health in patients diagnosed with diabetes, which had previously been based on inconclusive and scarce observations.

The researchers published their findings in the Canadian Medical Association Journal in December 2022, hoping their work might alleviate the demand and need for joint replacements in patients diagnosed with diabetes.

The international team that included Changhai Ding, MD, PhD, Clinical Research Center of Zhujiang Hospital, Southern Medical University in Guangzhou, China, and coauthors, focused efforts to establish whether metformin use was associated with a reduced risk of TKR or THR in diabetic patients. The researchers selected a 12-year time range (2000-2012) that included a cohort of 20,347 patients with diabetes who were prescribed metformin and 20,347 patients with diabetes who were not treated with metformin. All of the patients were selected from the Taiwan National Health Insurance Research Database, using Cox proportional hazards regression and propensity-score matching to balance potential confounders between those who were prescribed metformin and those who did not receive the diabetic drug. The team established an index date as 3 months after the first prescription of metformin and matched the subjects by age (within 3 years), sex, and time of prescriber visit for first diagnosis of type 2 diabetes mellitus (T2DM; within 180 days).

The authors provided insight into their hypothesis that diabetes had been identified as an independent risk factor for osteoarthritis (OA) without regard to BMI and that insulin resistance further contributes to the development of OA. Metformin is considered to be one of the most commonly prescribed medications to control diabetes, and its use associated with a decreased risk of cardiovascular disorders and inflammatory illnesses.

The team concluded that metformin use in patients with T2DM was associated with a significantly decreased risk of total joint replacement. They cautioned, however, that randomized, controlled clinical trials are still warranted to determine whether metformin is effective in decreasing the need for joint replacement in patients with OA. They also reported that when compared with subjects who did not use metformin, those who did had lower risks of TKR or THR (adjusted hazard ratio [HR] 0.70; 95% CI, 0.60-0.81 for TKR or THR; adjusted HR 0.71; 95% CI, 0.61-0.84 for TKR; adjusted HR 0.61; 95% CI, 0.41-0.92 for THR).

To summarize their findings, Dr. Ding wrote, “We found that metformin use in patients with type 2 diabetes mellitus was associated with a significantly reduced risk of joint replacement, suggesting a potential therapeutic effect of metformin in patients with osteoarthritis.”

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