medwireNews: Metformin use may protect against knee cartilage damage in obese people with knee osteoarthritis (OA), suggests an analysis of Osteoarthritis Initiative participants.
Metformin has been “widely used as first-line therapy for type 2 diabetes for over 50 years,” and “[i]n addition to its glucose-lowering effects, [it] modulates inflammatory and metabolic factors resulting in weight loss and reduced inflammation and plasma lipids,” explain the researchers.
The study among 818 individuals with radiographic knee OA (Kellgren–Lawrence grade ≥2) and obesity (BMI ≥30 kg/m2) found that, during 4 years of follow-up, the average annual rate of medial cartilage volume loss was significantly lower in metformin users (n=56) than in nonusers (n=762), at 0.71% vs 1.57%, when the results were adjusted for age, sex, BMI, pain score, Kellgren–Lawrence grade, self-reported diabetes, and weight change.
The fact that the beneficial effect of metformin use was independent of weight loss suggests “this is not the sole mechanism” involved in the preservation of knee cartilage, say Yuanyuan Wang (Monash University, Melbourne, Victoria, Australia) and co-investigators.
“The mechanisms may be via metformin’s effect on modulating inflammatory and metabolic pathways which in turn reduces inflammation and lowers plasma glucose and lipids,” they add.
The researchers found no difference in the rate of lateral cartilage volume loss between the two groups, but observed a nonsignificant reduction in the risk for total knee replacement over 6 years among metformin users relative to nonusers, after adjustment for age, sex, BMI, Kellgren–Lawrence grade, pain score, and self-reported diabetes.
Specifically, three (5.4%) metformin users and 88 (11.6%) nonusers received a total knee replacement during the observation period.
“Data from our study, together with data from previous human and animal studies, provide proof of concept that targeting obesity and obesity-related inflammatory, and metabolic pathways may have a disease-modifying effect in knee OA and that metformin might be a potential disease-modifying OA drug by affecting multiple pathological pathways in people with knee OA who are obese,” Wang and co-authors conclude in Arthritis Research & Therapy.
“Randomised controlled trials are needed to clarify this,” they add.
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Arthritis Res Ther 2019; 21: 127
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