OA is not rheumatoid arthritis (RA), an autoimmune disease in which the immune system attacks healthy cells. People with RA were excluded from the study.
Metformin Slows Knee Cartilage Loss
The study followed obese people with knee osteoarthritis for four years to see what effect metformin had on knee cartilage volume loss and for six years to assess the risk of total knee replacement. “We found that metformin users had about one-half the rate of knee cartilage loss [as compared with] those who did not use metformin. Slowing of knee cartilage loss is associated with less knee pain and lower risk of knee replacement surgery,” says lead study author YuanYuan Wang, PhD, senior research fellow in the department of epidemiology and preventive medicine at Monash University in Melbourne, Australia. The study additionally reported that “metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over six years.”
Non-Obese OA Patients May Benefit as Well
“Obese OA patients are the group of people most likely to benefit from metformin as they are enriched with obesity and obesity-related metabolic and inflammatory factors that metformin affects. Metformin may have an effect on non-obese OA patients but might be of less magnitude,” says Dr. Wang. Metformin might also be helpful for people with secondary OA, caused by a specific injury or trauma, obesity, genetics, or rheumatoid arthritis. “In our study we included participants with knee osteoarthritis assessed by X-ray. Some participants might have secondary osteoarthritis such as those with post-traumatic osteoarthritis,” says Wang.
Why Use a Diabetes Drug for OA?
The study researchers first thought to look at metformin as a possible therapy for OA because the diabetes drug provides multiple effects. In addition to its influence on reducing blood sugar levels, it also reduces weight, inflammation, and blood lipid levels. (A study published in June 2018 in the journal Arthritis Care & Research showed that if you are obese, losing 10 percent of your body weight or more can significantly improve your knee OA symptoms.) “As there is evidence that each of these — obesity, blood sugar, blood lipids, and inflammation — plays an important role in the progression of knee osteoarthritis, we hypothesized that metformin may slow the progression of the disease,” explains Wang.
Weight Loss Is Not the Whole Story
While the research team collected data on weight change over four years, the statistical analysis was controlled for weight loss, as there was slightly more of that in the metformin users than those who did not use metformin. “Our results suggest that the beneficial effect of metformin on cartilage was not simply explained by its effect on weight loss,” says Wang.
Hypothesis Needs More Study — Initial Finding Is Promising
This is a preliminary study, but it does build on previous work suggesting there are many different disease pathways in osteoarthritis. Wang says, “A patient with OA can take away the message that targeting metabolic and inflammatory pathways associated with obesity looks like a promising approach to slowing the progression of this disease and improving outcomes.”
