1. For patients with type 2 diabetes mellitus (T2DM), metformin use was associated with a significant reduction in risk of total knee replacement (TKR) and total hip replacement (THR).
Evidence Rating Level: 2 (Good)
Study Rundown: Osteoarthritis (OA) is one of the primary causes of chronic pain and disability, leading to high volumes of total knee replacement (TKR) and total hip replacement (THR) surgeries worldwide. While obesity is a risk factor for OA, diabetes mellitus is also a risk factor independent of obesity, with insulin resistance cited as a contributing factor. The leading treatment for type 2 diabetes mellitus (T2DM) is metformin, which ameliorates insulin resistance without altering weight, as well as reduces inflammation and protects cartilage. However, previous studies have been inconclusive in identifying a relationship between metformin use and improvement in OA outcomes. Therefore, this retrospective cohort study based in Taiwan examined the association between metformin use and risk of TKR or THR for patients with T2DM. The cohort consisted of patients diagnosed with T2DM over 13 years, drawn from a national health insurance database. Metformin users were then matched by age, sex, and time of diagnosis to metformin nonusers; however, data on patients’ glycemic control was not collected or analyzed. Overall, the results demonstrated a significant risk reduction for both TKR and THR for T2DM patients who used metformin.
In-Depth [retrospective cohort]: The study population included T2DM patients from the national database, diagnosed between 2000 and 2012, excluding those diagnosed under age 45. As well, metformin users were defined as individuals who were started on metformin within 180 days before or after their diagnosis of T2DM. These individuals were matched by age, sex, and time of diagnosis, with separate analyses using prescription time-distribution matching (PTDM) and propensity-score matching (PSM). In total, there were 20,347 patients in the metformin users and nonusers groups each. In comparisons of the two groups, metformin users had more severe disease, higher rates of hypertension and dyslipidemia, and higher baseline likelihood of being prescribed antihyperglycemic agents or insulin. Overall, the results generally demonstrated a significant risk reduction in joint replacement among metformin users. In the PTDM cohort, the TKR incidence was 2.96 vs 4.15 per 10,000 person-months for metformin users and nonusers respectively (hazards ratio 0.71, 95% CI 0.61-0.84); the THR incidence was 0.44 vs 0.83 per 10,000 person-months for users and nonusers respectively (HR 0.61, 95% CI 0.41-0.92). In the PSM cohort, there was a significant risk reduction for TKR in metformin users compared to nonusers (HR 0.76, 95% CI 0.62-0.92) but not a significant reduction for THR (HR 0.71, 95% CI 0.44-1.13). Altogether, this study showed that metformin use in T2DM patients is associated with a reduced risk of knee and hip total joint replacement.
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