Why is Metformin’s Magical Effects on Chronic Pain a Secret?

Selecting people with mildly abnormal hemoglobin A1C (prediabetic), authors found the introduction of Metformin 500 mg twice daily could dramatically relieve widespread pains. Article had to be pulled because consents were iffy and they didn’t have enough in “control group” to prove it didn’t work in non-diabetics. This was May 2019; I have been waiting for them to get consents and a big enough control group but treatment study was never republished. This has remained a secret.

Is insulin resistance the cause of fibromyalgia? A preliminary report
Miguel A. Pappolla et al
PLoS ONE 14(5): e0216079

I have included article should it disappear from net:


  • All but one were women aged 36-60
  • widepread “fibromylagia” pains
  • Hb A1C 5.7% – 6.5%
  • Usual Rx first was “norepinephrine reuptake inhibitors (amitriptyline, duloxetine or milnacipran [not available in Canada]) and/or membrane stabilizing agents (gabapentin or pregabalin), depending on tolerability or patients’ preference”.
  • Metformin was 500 mg twice daily
  • had a control group of 7 cases with normal Hb A1C that did not respond to metformin but I have left out as not enough cases to be a control group
  • Usual treatment for pain was tried first, then metformin added.


Comment – Had one female patient phone me some months ago confirming good response to metformin but I have hung back using it waiting for an unredacted report. Authors did publish a report angle about prediabetics getting more pain but the metformin angle was left out.  Have waited long enough. Given that these subjects were half better with standard treatment, metformin wasn’t as dramatic as it could have been.  I would try metformin first. Women with Polycystic Ovaries should easily qualify as there is insulin resistance there.

previously, it had been shown to help sciatica pains:

Taylor A, Westveld AH, Szkudlinska M, Guruguri P, Annabi E, Patwardhan A, Price TJ, Yassine HN.
The use of metformin is associated with decreased lumbar radiculopathy pain.
J Pain Res. 2013 Dec 9;6:755-63.

“The major finding was that metformin use was associated with a decrease in the mean of “pain now,” by -1.85 (confidence interval: -3.6 to -0.08) on a 0-10 visual analog scale, using a matched propensity scoring analysis and confirmed using a Bayesian analysis, with a significant mean decrease of -1.36 (credible interval: -2.6 to -0.03).”

  • There are a couple mice basic research article suggesting metformin works on brain and spinal cord contributors to chronic pain in males only:

Shiers, Stephanie, et al. “Neuropathic pain creates an enduring prefrontal cortex dysfunction corrected by the type II diabetic drug metformin but not by gabapentin.” Journal of Neuroscience 38.33 (2018): 7337-7350.
only in male mice

Inyang, Kufreobong E., et al. “The antidiabetic drug metformin prevents and reverses neuropathic pain and spinal cord microglial activation in male but not female mice.” Pharmacological research 139 (2019): 1-16.

  • It has been noted that metformin “activates adenosine monophosphate-activated protein kinase (AMPK) and through AMPK activation, inhibits the mammalian target of rapamycin (mTOR) pathway. Recent literature has explored metformin as an option in pain management, given its role in the AMP-activated protein kinase (AMPK) pathway and its ability to modulate pain in animal models.”
  • I previously wrote about how metformin can help mitochondrial function which helps fibromylagia:

Fibromyalgia (FM) – Mitochondrial Dysfunction Helped by Metformin and Weight Loss

and helps Bipolar:
Metformin is Mitochondrial Enhancer and Helps Bipolar Depression

I thought wow when I read article before it was redacted and distributed it to colleagues. Now I put it here for everyone to decide.


Metformin’s effects on pain have been confirmed:

Musculoskeletal pains:

Carvalho‐e‐Silva, Ana Paula, et al. “The effect of the anti‐diabetic drug metformin on musculoskeletal pain: A cross‐sectional study with 21,889 individuals from the UK biobank.” European Journal of Pain 25.6 (2021): 1264-1273.

Arthritis various forms:
Kim JW, Choe JY, Park SH. Metformin and its therapeutic applications in autoimmune inflammatory rheumatic disease.
Korean J Intern Med. 2022;37(1):13-26.

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