Metformin use was linked to a reduced rate of medial cartilage loss that may, in turn, reduce the risk for total knee replacement among patients with osteoarthritis who are obese, according to data published in Arthritis Research & Therapy.
“Current treatments for osteoarthritis are modestly effective in pain relief with short-term effects, with no treatments that slow disease progression,” Yuanyuan Wang, MD, PhD, MBBS, MMed, of Monash University, in Melbourne, Australia, told Healio Rheumatology. “There is an unmet need for effective treatments that can reduce joint pain and slow the structural progression.”
He added, “Metformin has been used in clinical practice for over 50 years with good safety profile. In additional to its effect on reducing blood sugar levels, it also reduces weight, inflammation and blood lipid levels; as there is evidence that each of these plays an important role in the progression of knee osteoarthritis, we hypothesized that metformin may slow the progression of knee osteoarthritis.”
To determine whether treatment with metformin was linked to a 4-year loss of knee cartilage volume, as well as the 6-year risk for total knee replacement, among patients with OA and obesity, Wang and colleagues analyzed data from the Osteoarthritis Initiative. According to the researchers, the Osteoarthritis Initiative is a multicenter observational cohort study of knee OA, with 4,796 participants aged 45 to 79 years at baseline.
Wang and colleagues studied participants with radiographic knee OA who were obese. They included 818 participants, of whom 56 reported using metformin regularly at baseline, as well as at the 1- and 2-year follow-up. The researchers evaluated medial and lateral cartilage volume using MRI at baseline and 4 years. Total knee replacement was assessed during a period of 6 years.
According to the researchers, patients who used metformin demonstrated a lower rate of medial cartilage volume loss, with 0.71% per annum, compared with nonusers, with 1.57% (difference = –0.86%; 95% CI,–1.58 to –0.15). The researchers arrived at this figure after adjusting for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes and weight change over 4years, they wrote.
“We found that metformin users had about half the rate of knee cartilage loss compared to those who did not use metformin,” Wang said. “Slowing of knee cartilage loss is associated with less knee pain and lower risk of knee replacement surgery.”
According to researchers, metformin treatment was associated with a trend toward a significantly reduced 6-year risk for total knee replacement (OR = 0.3; 95% CI, 0.07-1.3), after adjusting for age, gender, BMI, Kellgren-Lawrence grade, pain score and self-reported diabetes.
“Our results will need to be confirmed in randomized controlled trials, however, it builds on previous work suggesting many different disease pathways in knee osteoarthritis, Wang said. “A patient with osteoarthritis 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 patient outcomes.”
Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiative—a prospective cohort study
Anyuan Wang, Sultana Monira Hussain, Anita E. Wluka, Yuan Z. Lim, François Abram, Jean-Pierre Pelletier, Johanne Martel-Pelletier and Flavia M. Cicuttini