Diabetes Drug Metformin Reduces Knee Pain From Osteoarthritis in Study

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On April 29, 2025

A new study suggests that the common, inexpensive diabetes medication metformin may help some people with chronic knee pain from osteoarthritis.

Findings recently published in JAMA showed that taking these pills daily over the course of six months lowered pain levels, eased stiffness, and improved knee function in people who are overweight or have obesity.

“Primary care physicians are very familiar with metformin, which is a low-cost, safe medication,” says lead researcher Flavia Cicuttini, PhD, who heads Monash University’s Musculoskeletal Unit and is head of rheumatology at The Alfred Hospital in Melbourne, Australia. “It can be provided to help patients with knee pain in addition to other treatments, including encouraging physical activity.”

Osteoarthritis (OA) is a degenerative joint disease that is more likely to affect people who are overweight or have obesity. Excess weight heightens the pressure on the joint, and that increase in stress can possibly hasten the breakdown of cartilage.

Osteoarthritis interferes with basic activities such as walking, and makes people less confident in their bodies, according to the Arthritis Foundation.

Metformin Cut Knee Pain in Half

The new study builds on prior research suggesting that metformin can help alleviate osteoarthritis in people with diabetes.

The current investigation involved 107 adult patients without diabetes — 73 women and 34 men who were an average age of 59. Participants had a body mass index of 25 or higher (which is considered overweight) and knee pain for six months.

They were divided into two groups, with one group taking up to 2,000 milligrams of metformin daily and the other group taking a placebo (dummy pill).

Knee pain was measured on a 0 to 100 scale, with 100 being the worst. The metformin group reported a 31.3 point reduction in pain after six months, compared with 18.9 for the placebo group.

Study authors called the decrease in pain “significant” with a 52 percent reduction in knee pain in the metformin group and a 32 percent reduction in the placebo group.

A decrease in knee pain in the placebo group is an effect often seen in trials of osteoarthritis, as people who enter a study with pain tend to improve over time even without intervention, according to the researchers. The effect, however, was much greater in the metformin group.

Dr. Cicuttini adds that the magnitude of metformin’s effect was considered moderate, yet higher than that seen with anti-inflammatory medications and acetaminophen (Tylenol).

“Also, many people can’t use anti-inflammatory medications due to safety issues,” she says.

Treatment Is a Possible Way to Avoid or Delay Knee Replacement

While there is no cure for osteoarthritis, people can ease symptoms with medications, including analgesics, nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen), and corticosteroids. Exercise and weight loss can also help.

The study authors caution, however, that effective treatments for osteoarthritis are limited, which leads to more people having knee replacements early in the course of the disease.

“This results in a number of problems,” says Cicuttini.

The researchers estimate that patient dissatisfaction with knee replacements can range from 20 to 30 percent because many people continue to have symptoms and their expectations are not met. They highlight evidence suggesting the rate of patient dissatisfaction is 2.5 times higher in those who have knee replacement earlier in the course of their osteoarthritis rather than later.

Even though knee replacements can be long-lasting — about 20 years — they tend to endure better in older people than in younger people due to differences in activities that people do at different ages, notes Cicuttini.

“Earlier knee replacement means that the person is at increased risk of needing revision surgery or a ‘redo,’ which costs 3.5 times that of the first knee replacement, with worse results,” she says. “Knee replacements are an excellent procedure for those that really need it, but the idea is to try and time it so they only need one for that knee over their lifetime.”

The results from this analysis suggest that metformin could lessen knee pain enough so that patients can be more physically active and delay potential knee surgery.

More Expansive Study Needed to Confirm Results

Rajat Bhatt, MD, a rheumatologist in Richmond, Texas, who is affiliated with Memorial Hermann Health System Health, notes that these findings are limited in that they are based on a relatively small group of participants.

“The study needs to be replicated on a larger scale over a longer period to really see what the patient benefit is,” says Dr. Bhatt, who was not involved in the research.

While metformin may be useful in reducing osteoarthritis pain, Absalon Gutierrez, MD, associate professor of endocrinology, diabetes, and metabolism at UTHealth Houston, stresses that the drug is not a cure.

“It is unclear whether metformin treats the underlying cause or not,” says Dr. Gutierrez, who was not involved in the study.

Findings from this and other research, however, suggest that the drug improves the metabolism of joints and reduces low grade inflammation.

Metformin is also known to promote weight loss, which could have been a contributing factor in decreasing pain. People in this study taking the drug lost an average of nearly four pounds compared with about two and a half pounds in the placebo group.

Should You Talk to Your Doctor About Metformin?

The U.S. Food and Drug Administration has not approved metformin for osteoarthritis therapy, but patients may consult with their physician about using the drug off label.

Metformin has already been repurposed for treatment of gestational diabetes, nonalcoholic fatty liver disease, weight gain issues caused by antipsychotic medication, polycystic ovary syndrome (PCOS), and some cancer cases.

“The study adds to growing indications besides diabetes for this relatively safe medication,” says Ajaykumar Rao, MD, chief of the section of endocrinology, diabetes, and metabolism at the Lewis Katz School of Medicine at Temple University in Philadelphia, who was not involved in the study. “We still need some further research to clarify how metformin actually works on a cellular level to benefit patients.”