Can Metformin Lower Need for Joint Replacement in Diabetes? - Medscape

Metformin whitethorn assistance trim hazard for full associated replacement successful patients with type 2 diabetes (T2D), information suggest.

Over a 24-month follow-up period, metformin usage was associated with a 30% alteration successful the hazard of full genu and hep replacements, according to Changhai Ding, MBBS, MMed, MD, subordinate manager of the Menzies Institute for Medical Research astatine the University of Tasmania successful Hobart, Australia, and colleagues.

"Randomized controlled objective trials successful patients with osteoarthritis are warranted to find whether metformin is effectual successful decreasing the request for associated replacement," wrote the investigators.

Their findings were published online December 19 successful the Canadian Medical Association Journal.

Low Doses Beneficial

The investigators identified patients diagnosed with T2D from 2000 to 2012 successful the Taiwan National Health Insurance Research Database and compared those who utilized metformin with those who did not. They utilized medicine time-distribution matching and propensity-score matching to equilibrium imaginable confounders betwixt users and nonusers.

The survey included 20,347 metformin-treated participants and 20,347 nonusers. The mean property astatine baseline was 63 years, and 49.8% of participants were women. Metformin users tended to person much terrible diabetes. Common comorbidities successful the cohort included hypertension and hyperlipidemia, but lone astir 16% successful some groups had osteoarthritis. At baseline, participants besides utilized assorted analgesics, arsenic good arsenic different diabetes drugs ranging from sulfonylureas to insulin.

Compared with nonusers, metformin users had had a 30% little hazard of full genu oregon hep replacement (adjusted hazard ratio [HR], 0.70). The incidence of total genu replacement among metformin nonusers and users was 4.15 per 10,000 person-months and 2.96 per 10,000 person-months, respectively. The incidence of total hep replacement was 0.83 per 10,000 person-months successful nonusers and 0.44 per 10,000 person-months successful users.

By associated type, the adjusted HR was 0.71 for full genu replacement and 0.61 for full hep replacement among metformin users.

The effect was observed astatine regular doses of little than 1 g, arsenic good arsenic regular doses of 1 g oregon more. "This suggests that metformin astatine a little dosage could person effects connected osteoarthritis," Ding told Medscape Medical News. "Metformin is simply a safe, well-tolerated oral medication, adjacent astatine higher but routinely utilized dosages. Therefore, for archetypal objective trials, we inactive urge the efficacy of metformin astatine regular dosages connected genu osteoarthritis. If the effects are confirmed, we whitethorn research whether a little dosage of metformin is effective."

Similar results emerged from propensity-score matching analyses and sensitivity analyses of 10,163 participants successful each attraction radical utilizing inverse probability-of-treatment weighting and competing hazard regression.

The biologic mechanisms linking metformin and osteoarthritis person yet to beryllium clarified, Ding explained. "Multiple mechanisms whitethorn beryllium involved, including anti-inflammation, sustaining adenosine 5'-monophosphate-activated macromolecule kinase enactment successful chondrocytes and dorsal basal ganglia, and regulating metabolism."

A erstwhile survey suggested an relation betwixt metformin and reduced yearly nonaccomplishment of medial cartilage volume, and different recovered an relation betwixt metformin and reduced associated replacement surgery, said Ding. But different survey reported nary important relation betwixt metformin usage and osteoarthritis hazard successful patients with T2D. Recently, a retrospective cohort survey by Li et al recovered that metformin users with diabetes had a 19% little hazard for full genu replacement than nonusers.

Ding's radical has begun a randomized objective proceedings to spot whether metformin tin alleviate tibiofemoral cartilage measurement loss successful overweight patients with osteoarthritis.

No Uniform Indications

Commenting connected the existent findings for Medscape, Grace Hsiao-Wei Lo, MD, an adjunct prof of immunology, allergy, and rheumatology astatine Baylor College of Medicine successful Houston, Texas, called the observational survey "thought-provoking." She had concerns astir the mode it was conducted, however, including the perchance problematic features of the tiny percent of the T2D cohort who had osteoarthritis. Another interest was the information that the investigators lone examined metformin, though patients utilized assorted different diabetic and analgesic drugs that mightiness person had an effect. Metformin's effect connected osteoarthritis whitethorn effect partially from its modest weight-loss effects, said Lo, who was not progressive successful the study.

"Another contented with the survey is that determination is nary acceptable denotation of the request for full genu oregon hep replacement. Each surgeon has a antithetic standard," she added. "And there's tons of grounds that replacements are mostly babelike not connected request but connected the involvement of participants. "So, it's not needfully that a diligent needs full associated replacement, it's that they privation it."

Observational studies similar this 1 are a agelong mode from getting america to the prescribing of metformin specifically to forestall oregon mitigate osteoarthritis, David T. Felson, MD, MPH, a rheumatology researcher and a prof of medicine astatine Boston University, Boston, Massachusetts, told Medscape. Felson was not progressive successful the study.

"The drug's mechanisms successful osteoarthritis are inactive unclear. Its effect whitethorn beryllium related to adenosine 5'-monophosphate-activated macromolecule kinase activity," helium said. "The cause has pleiotropic effects and is safely utilized to dainty different diseases specified arsenic polycystic ovarian syndrome. It whitethorn person antisenescence properties, since it's been shown to widen beingness a spot successful animals." That said, Felson added, "Like statins, it's not going beryllium added to the drinking h2o anytime soon!"

This survey was supported by the National Natural Science Foundation of China, Guangzhou Science and Technology Program, Guangdong Basic and Applied Basic Research Foundation, and Wu Jieping Medical Foundation Program. Ding, Lo, and Felson reported nary competing interests.

CMAJ. Published online December 19, 2022. Full text.

Diana Swift is simply a freelance aesculapian writer based successful Toronto, Ontario, Canada.

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