Beyond diabetes, metformin may prove to be a ‘wonder drug'
New research is suggesting that metformin may hold promise in treating or preventing a whole host of conditions in patients with and without type 2 diabetes. Studies show metformin may be cardioprotective in patients with diabetes and beneficial in the presence of stable congestive heart failure. The agent also may help to increase pregnancy rate in polycystic ovary syndrome, provide breast and prostate cancer benefits, and offer neuroprotection that may reduce dementia and stroke risk, Akiyode said.
Nir Barzilai, MD, is exploring whether metformin can target and delay aging, to decrease the incidence of age-related diseases in general, rather than merely decrease the incidence of diabetes. Photo courtesy of Albert Einstein College of Medicine printed with permission.
Nir Barzilai, MD, an endocrinologist and director of the Institute for Aging Research at the Albert Einstein College of Medicine, said he hopes to work with the FDA to conduct an NIH/American Federation for Aging Research metformin trial later this year — Targeting Aging with Metformin (TAME) — that will demonstrate the agent's ability to delay the onset of comorbidities related to aging, thereby reducing the period of morbidity at the end of life.
“If metformin can target and delay aging, its administration should be associated with fewer age-related diseases in general, rather than merely the decreased incidence of a single disease,” Barzilai and colleagues wrote in a study published in the June 2016 issue of Cell Metabolism. “Data from several randomized clinical trials and multiple observational studies provide evidence for such an effect, which would not be expected from glucose lowering alone.”
Endocrine Today spoke with experts who discussed the latest research demonstrating the nondiabetic benefits of metformin and the theories behind possible mechanisms.
Metformin's history, mechanism
The use of what would eventually become metformin dates to the Middle Ages, when herbalists first derived extracts from Galega officinais, a plant known alternatively as French lilac, false indigo and Spanish sainfoin, to treat frequent urination. The plant's active ingredient — guanidine — was first isolated in the 1800s and later synthesized as the less-toxic metformin. The drug was approved in France and the United Kingdom in 1957 and 1958, respectively, but it would be another 37 years before the FDA would approve the agent for use in the United States.
Despite the initial resistance to the drug, the FDA has been more open recently to considering studies that could examine other indications for metformin, through trials like TAME.
“The FDA has shown increasing flexibility in recent years with regard to metformin, surprisingly so, considering its original position back in the 1980s when it vowed never to approve the drug,” Alan J. Garber, MD, PhD, FACE, chief medical editor of Endocrine Today, said in an interview. “It was a surprisingly firm position, not necessarily grounded in observational science, but was related to the rather startling toxicity of [the drug's] cousin, phenformin.” Phenformin was withdrawn from most markets in the late 1970s because of a high risk for lactic acidosis in patients.
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