Metformin for Pain? Study Says: Not Yet

Although some studies have hinted at a possible role for metformin in pain management, a recent investigation found no difference in pain scores among diabetic patients who used metformin and those who did not

Metformin is one of the most widely prescribed anti-diabetic drugs in the world. Its safety, effectiveness, and relatively low side effect profile have made it an international superstar and the gold standard for treatment of type 2 diabetes. Although almost exclusively prescribed for treatment of diabetes, metformin has recently been the subject of clinical trials for treatment of breast cancer, polycystic ovary syndrome, non-alcoholic fatty liver disease, and premature puberty. All of those conditions are related to the levels of insulin produced by the body.

But could metformin’s star still be on the rise? If the drug can be clinically proven to treat pain, the answer would be a definitive “yes.” There is strong connection between diabetes and pain; patients with diabetes are nearly twice as likely to have arthritis, and the disease causes musculoskeletal changes that lead to symptoms such as joint pain and stiffness, and swelling in fingers, shoulders, and feet.

One pharmacological target for the treatment of chronic pain conditions is the kinase adenosine monophosphate activated kinase (AMPK). Metformin acts via AMPK, pointing to a possible clinical rationale for its use in pain patients. As yet, there is little clinical evidence that metformin can effectively treat pain, although a 2013 study in the Journal of Pain Research was among the first to find a correlation between metformin and pain relief. That study, which looked at lumbar spine pain, concluded that, “Patients on metformin showed a non-statistically significant trend toward decreased pain on a variety of… pain descriptors. Our proof-of-concept findings suggest that metformin use is associated with a decrease in lumbar radiculopathy pain, providing a rationale for larger retrospective trials in different pain populations… to test the effectiveness of metformin in reducing neuropathic pain.”

This is a very promising result in lumbar radiculopathy pain, which is notoriously difficult to treat with existing therapeutics. But much further study is needed to establish a stronger connection between metformin and relief of other types of pain.

A recent study in Pain Medicine reveals that making this connection isn’t a slam-dunk. The study involved a phone survey of 329 participants with diabetes. The researchers used the Brief Pain Inventory to assess for pain intensity ratings, LeedsAssessment of Neuropathic Symptoms and Signs to screen for neuropathy; and the Personal Health Questionnaire (PHQ8) Depression Scale to assess for depression.

The survey concluded that in a subset of those with neuropathic pain, there were no differences in pain scores found between groups. However, the authors note that future studies at higher dosages than the average 1,432 mg of metformin will be necessary. “Given the anti-nociceptive effects of metformin in the animal models of pain, and the relative safety of metformin, future research should evaluate the effect of the higher dose of metformin as a potential analgesic,” the study authors wrote.

For now, at least, metformin’s next star turn will have to wait.