By Joseph E. Scherger, MD, MPH

Core Faculty, Eisenhower Health Family Medicine Residency Program, Eisenhower Health Center, La Quinta, CA; Clinical Professor, Keck School of Medicine, University of Southern California, Los Angeles

SYNOPSIS: An analysis of patients taking metformin for diabetes showed they were less likely to report back, knee, neck/shoulder, or multisite musculoskeletal pain.

SOURCE: Carvalho-E-Silva AP, Harmer AR, Ferreira ML, Ferreira PH. The effect of the anti-diabetic drug metformin on musculoskeletal pain: A cross-sectional study with 21,889 individuals from the UK Biobank. Eur J Pain 2021; Feb 9. doi: 10.1002/ejp.1747. [Online ahead of print].

A team from Australia studied a database that included 21,889 patients with type 2 diabetes collected from 2006-2010 in England, Wales, and Scotland. Medications, symptoms, and lifestyle factors were recorded. Musculoskeletal (MS) pain was recorded for the back, knee, hip, and neck/shoulder. It was considered significant if the pain interfered with usual activities over three months.

Patients using metformin reported significantly lower rates of MS pain in all these sites vs. people with diabetes on other treatment. The associations were significant for both men and women, and generally stronger in women. This association with metformin alleviating MS pain has been shown in other studies.1 Metformin may influence pain by triggering activated protein kinase (AMPK).2 AMPK may reduce the excitability of peripheral nociceptors and mechanical allodynia in neuropathic pain.3


The many positive pleiotropic effects of the inexpensive and effective drug metformin for type 2 diabetes are fortuitous. I tell patients who may be hesitant to take this drug that it may improve their health in several ways, and help them live longer. There is strong biology to support these effects.4

Metformin has become a popular anti-aging drug in part because of the work of Harvard biologist David Sinclair, who uses metformin to lengthen lifespan.5 A recent article in Internal Medicine Alert indicated hospitalized patients on metformin were at a lower risk of mortality.6

Patients should take metformin with or after a meal to avoid the gastrointestinal side effects. The 500 mg dose is used in prediabetes and for anti-aging. Start with 500 mg in people with type 2 diabetes so they can adjust to the drug for about two weeks. Then, increase the dose to 1,000 mg, both twice daily. 


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  2. Ouyang JY, Parakhia RA, Ochs RS. Metformin activates AMP Kinase through inhibition of AMP deaminase. J Biol Chem 2011;286:1-11.
  3. Viollet B, Guigas B, Sanz Garcia N, et al. Cellular and molecular mechanisms of metformin: An overview. Clin Sci 2012;122:253-270.
  4. Hattori Y, Hattori K, Hayashi T. Pleiotropic benefits of metformin: Macrophage targeting its anti-inflammatory mechanism. Diabetes 2015;64:1907-1909.
  5. Sinclair DA, LaPlante MD. Lifespan: Why We Age — and Why We Don’t Have To. Simon & Schuster; 2019.
  6. Ulrich A. Prior metformin use in patients with diabetes hospitalized for COVID-19. Internal Medicine Alert 2021;43:25-26.