Metformin Protective Against Joint Replacement in Type 2 Diabetes

Among people with type 2 diabetes, use of metformin might help to stave off total joint replacement, a population-based cohort study showed.

Among over 40,000 patients, daily metformin was associated with a 30% lower risk for total knee and hip replacement compared with no metformin (adjusted HR 0.70, 95% CI 0.60-0.81) over a median follow-up of 54 months, reported Changhai Ding, MD, PhD, of Southern Medical University in Guangzhou, China, and colleagues.

Broken down, use of metformin was linked to lower risks for both total knee replacement (aHR 0.71, 95% CI 0.61-0.84) and total hip replacement (aHR 0.61, 95% CI 0.41-0.92), they noted in the Canadian Medical Association Journal.

“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 OA [osteoarthritis],” the researchers wrote. “Randomized controlled clinical trials are warranted to determine whether metformin is effective in patients with OA.”

The incidence of hip or knee joint replacement was 4.99 per 10,000 person-months for non-users versus 3.40 per 10,000 person-months for patients on metformin.

The researchers also calculated whether or not this relationship was dose-dependent, separating models for patients taking less than 1 g of metformin per day versus 1+ g per day, but found these results to be “inconsistent.”

“Metformin could decrease the risk of total joint replacement among patients with diabetes mellitus by multiple mechanisms, including by reducing inflammation, by sustaining adenosine 5′-monophosphate-activated protein kinase activity in chondrocytes and by regulating metabolism,” they explained.

Ding and team also noted that “metformin has been studied in patients without diabetes mellitus and [it] was found to be safe.”

“Trials of metformin for the prevention of diabetes mellitus and for weight reduction among patients with obesity and without diabetes mellitus showed that doses of 1.7-2.5 g/d could be prescribed without increases in incidence of hypoglycemia or lactic acidosis,” they wrote.

The Taiwan-based study used data from 40,694 patients included in the National Health Insurance Research Database, split evenly between those taking metformin and those not. Mean age was 63, and 49.8% were women. People with type 1 diabetes were excluded, as were those younger than 45 years at the time of diabetes diagnosis.

Exposure to metformin was defined as use within 180 days after or before a new type 2 diabetes diagnosis from January 2000 to December 2012.

About 16% of the cohort had osteoarthritis at baseline. Some of the most common comorbidities included hypertension, hyperlipidemia, depression, and chronic obstructive pulmonary disease. Less than 1% of the cohort had obesity.

More than half of patients on metformin were on a sulfonylurea, while only 7% of those not on metformin were taking one. Patients on metformin were more likely to also be taking insulin, α-glucosidase inhibitors, thiazolidinediones, or DPP-4 inhibitors.

The models were adjusted for baseline covariates including sex, age, urbanization, insurance type, severity of diabetes complications, comorbidities, medications for pain management, other oral antihyperglycemics, and insulin use.