Posted on 05/15/2025 5:14:15 AM PDT by Red Badger
A clinical trial led by Monash University found that the common diabetes drug metformin significantly reduced knee pain in people with osteoarthritis and overweight or obesity, potentially delaying the need for knee replacements. Over six months, participants taking metformin experienced greater pain relief than those on placebo, offering a promising, low-cost alternative treatment.
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Metformin may reduce knee pain in overweight patients with osteoarthritis, offering a low-cost alternative to early knee replacement surgery, according to a Monash University trial.
A widely used diabetes medication may help relieve knee osteoarthritis (OA) pain in people who are overweight or obese, potentially delaying the need for knee replacement surgery, according to new research led by Monash University.
The study, published in JAMA, investigated the effects of metformin, a drug commonly prescribed for type 2 diabetes, on knee pain. Over a six-month period, researchers conducted a randomized clinical trial comparing metformin to a placebo in adults with symptomatic knee OA and no history of diabetes.
Conducted entirely via telehealth, the community-based trial enrolled 107 participants (73 women and 34 men) with an average age of 60. Participants received either a daily dose of up to 2000 mg of metformin or a placebo. None had diabetes.
Measured Impact on Pain Levels
Knee pain was measured on a 0-100 scale, with 100 being the worst. The metformin group reported a 31.3 point reduction in pain after six months, compared to 18.9 for the placebo group. This was considered a moderate effect on pain.
“These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity,” the researchers found. “Because of the modest sample size, confirmation in a larger clinical trial is warranted.”
Lead researcher Professor Flavia Cicuttini, who heads Monash University’s Musculoskeletal Unit and is The Alfred’s Head of Rheumatology, said the results showed that metformin was a potentially new and affordable way to improve knee pain in those with knee OA and overweight or obesity.
Knee OA treatments include lifestyle approaches such as exercise and weight loss, which patients often find difficult, and medications such as paracetamol, topical anti-inflammatory creams, and oral anti-inflammatory medications which have small benefits and may be unsuitable for some patients for safety reasons.
No new OA drugs have been approved in Australia since Celebrex (celecoxib) and Vioxx (rofecoxib) in the late 1990s.
Implications for Surgery and Healthcare Costs
Professor Cicuttini said effective treatments that improved knee pain in osteoarthritis were limited. She said this led some patients and their doctors to seek alternative treatments including surgery.
This resulted in major problems managing knee OA in Australia and internationally, including an increase in the rate of knee replacements performed for earlier stages of OA. This was based on the idea that effective treatments for knee OA were limited and that knee replacements lasted a long time
“At first glance, this may seem reasonable, but it is a major problem because patient dissatisfaction with knee replacements is already high at between 20-30 per cent, even when the operation is technically perfect*,” Professor Cicuttini said. “Dissatisfaction rates are highest when the operation is done for early knee OA.
“To go through the effort and cost of a big operation like a knee replacement, only to be unhappy with the results because of ongoing pain and symptoms, is definitely low-quality care. Doing a knee replacement earlier also increases the potential need for the procedure to be redone.
“This costs about 3.5 times as much, so about $70,000 compared to $20,000, and the results tend not to be as good as the first time. The best outcome for patients is to delay the knee replacements until it is absolutely needed.”
Potential for Broad Implementation
Professor Cicuttini said metformin now provided GPs an alternative they could offer patients in addition to managing weight and increasing activity. “Metformin works in a number of ways on the knee, including affecting low grade inflammation and other metabolic pathways that are important in knee OA,” she said. “It is a different way to treat knee OA pain.
“GPs are very familiar with metformin, which is a low-cost, safe medication. It could be provided to patients in addition to other treatments they use and has the potential to delay people having knee replacements before they are absolutely needed. If people on metformin have less knee pain and are able to do more physical activity, then knee replacements can wait.”
Professor Cicuttini and her colleagues are now working with consumers, GPs, orthopaedic surgeons and other healthcare professionals to introduce metformin into the knee OA management pathway in order to improve patient outcomes and potentially better target knee replacements. Metformin could be used ‘off label’ after discussions between patients and their doctor.
“Metformin is safe and well tolerated,” she said. “It is used safely in other non-diabetes conditions such as polycystic ovarian syndrome. Metformin could be provided simply and safely using a telehealth approach, as we did in our study, meaning that it could be provided across the community, including in regional and remote areas.”
About knee osteoarthritis (OA)
Effective therapy for knee OA is limited, with a growing international trend toward knee replacements on patients with even milder cases[1], despite recommendations that surgery be reserved for symptomatic end-stage OA[2]. This trend has been partly explained by the lack of effective treatments for knee OA and improved longevity of knee replacements.
Other research has found pain is an ‘omni- present’ feature of knee osteoarthritis and perceived to interrupt and deter daily activities such as walking, making people less confident in their bodies[3]. Current guidelines leave the timing and patient appropriateness for surgery to the discretion of the treating clinicians[4]. However, a systematic review and meta-analysis provided consistent evidence that mild radiological OA was a major contributor to the 20-30% patient dissatisfaction with knee replacements, including persisting pain[5].
About metformin
Metformin is a safe, inexpensive, well-tolerated oral medication that has been first-line therapy for type 2 diabetes for more than 60 years. Metformin reduces the production of glucose produced and released by the liver, insulin resistance, and low blood-sugar levels. It causes modest weight loss and reduces inflammation in people with and without diabetes. Other effects of metformin, such as anti-inflammatory properties, and improved glucose and lipid metabolism, such as reduced insulin resistance, may reduce knee pain in osteoarthritis[6].
Reference:
"Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial” by Feng Pan, Yuanyuan Wang, Yuan Z. Lim, Donna M. Urquhart, Mahnuma Mahfuz Estee, Anita E. Wluka, Rory Wolfe and Flavia M. Cicuttini, 24 April 2025, JAMA.
DOI: 10.1001/jama.2025.3471
This research was supported by the National Health and Medical Research Council (NHMRC).
Shohat N, Heller S, Sudya D, Small I, Khawalde K, Khatib M, Yassin M. Mild radiographic osteoarthritis is associated with increased pain and dissatisfaction following total knee arthroplasty when compared with severe osteoarthritis: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2022;30:965-81.
Kloppenburg M, Namane M, Cicuttini F Osteoarthritis. Lancet. 405:71-85, 2025 Jan 04.59.
Wallis JA, Taylor NF, Bunzli S, Shields N. Experience of living with knee osteoarthritis: a systematic review of qualitative studies. BMJ Open. 2019 Sep 24;9(9):e030060. doi: 10.1136/bmjopen-2019-030060. PMID: 31551381; PMCID: PMC6773287
Usiskin I. Surgical Treatments for Osteoarthritis. Eur J Rheumatol. 2023;11:S41-7.
Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ Open. 2012;2:e000435.
Lim YZ, Wang Y, Estee M, Abidi J, Udaya Kumar M, Hussain SM, Wluka AE, Little CB, Cicuttini FM. [Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of pre-clinical and human studies. Osteoarthritis Cartilage.2022 11];30(11):1434-1442
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Metformin Ping!..............
I was telling Mrs.V_TWIN just the other day, my knees are pretty much the only part of my body I DON’T have pain in. 😁
I wonder what high percentage of patients with osteoarthritis and awaiting knee replacement are also overweight and on metformin for type 2 diabetes? A large number I reckon.
Metformin seems to be useful for a whole slough of things!.................
Rx’s usually do not address root causes and actually heal or remove the problem. RX’s do all have side effects, most times slow over time and that way doctors keep making more money off of you as new symptoms arise.
Lose the weight with behavior modification, and exercise like pushing away from the trough earlier than normal....
Metformin is being studied as a wonder drug. It helps so many conditions. It is cheap. It is widely available.
Helps with constipation too. ;0)
And for this reason they will 'discover' a serious side effect hitherto unknown and remove it from the market immediately...............
Skeptical that it will re-grow cartilage lost to old age.
Funny what happens when you do something to alleviate the effects of inflammation - /s - but there’s no excuse to take a pill for what is indisputably “lifestyle disease” (type 2).
I have flat out bone on bone in my left knee. getting the replacement done in july. Don’t know how metformin can help.
Stages of OA
https://www.verywellhealth.com/stages-of-osteoarthritis-5095938
This sounds like what the doc was telling the wife last week.
Metformin still reminds me of the Carpet Bagger tried to sell Josie Wales a $1 bottle of cure all. This stuff works good on everything! (Still waiting for the pin to drop.)
Around 15 years ago (at age 65) I had OA so bad that a doctor told me I would need the knee replacement. I started taking 3000mg of glucosamine HCl per day and within three months my knees were just fine. I still take 3000mg once per week, and have had no knee problem since.
Anticancer, as well.
Uh Oh
I told someone about this when it was posted last week, she said she had heard of the medication, but that it had bad side effects
More common side effects:
abdominal or stomach discomfort
cough or hoarseness
decreased appetite
diarrhea
fast or shallow breathing
fever or chills
general feeling of discomfort
lower back or side pain
muscle pain or cramping
painful or difficult urination
sleepiness
Less common side effects:
anxiety
blurred vision
chest discomfort
cold sweats
coma
confusion
cool, pale skin
depression
difficult or labored breathing
dizziness
fast, irregular, pounding, or racing heartbeat or pulse
feeling of warmth
headache
increased hunger
increased sweating
nausea
nervousness
nightmares
redness of the face, neck, arms, and occasionally, upper chest
seizures
shakiness
slurred speech
tightness in the chest
unusual tiredness or weakness
Rare side effects:
behavior change similar to being drunk
difficulty with concentrating
drowsiness
lack or loss of strength
restless sleep
unusual sleepiness
More common side effects:
acid or sour stomach
belching
bloated
excess air or gas in the stomach or intestines
full feeling
heartburn
indigestion
loss of appetite
metallic taste in the mouth
passing of gas
stomachache
stomach upset or pain
vomiting
weight loss
Less common side effects:
abnormal stools
bad, unusual, or unpleasant (after) taste
change in taste
difficulty with moving
discoloration of the fingernails or toenails
flu-like symptoms
joint pain
rash
sneezing
stuffy or runny nose
swollen joints
Do Not Taunt Metformin!
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