Three or four years ago, a buzz started building that metformin could be a potential fountain of youth. In 2011, a group of researchers in oncology in St. Petersburg, Russia, found that metformin could prevent the advancement of cancer in mice, thereby increasing their lifespans. In 2012, several online health advocates passionately accused the FDA of sinister motivations for preventing the makers of metformin from advertising it as an anti-cancer and anti-vascular disease medicine.
There appears to be no such conspiracy. This year, the FDA registered a human trial of metformin for a placebo-controlled study involving people with diabetes and those without to test whether the drug can promote overall longevity. The trial will be undertaken at the Einstein College of Medicine at Yeshiva University in New York, and is at publication time still recruiting participants.
If the results prove favorable, it will mark another dynamic chapter in the storied history of the drug. Metformin is said to have first been created in France in the 16th century, when it was made from an extract of the plant galega officinalis, known as goat’s rue or French lilac. As an herbal remedy, it was used in treating a urinary disorder with a name derived from Greek that meant “sieve,” which may in fact be what’s known in modern times as diabetes insipidus. French pharmacy labs began to make a synthetic formulation in the 1920’s, but then, according to the lore, the discovery of insulin overshadowed it as a more promising diabetes remedy. Efforts to develop the synthetic version diminished in the worldwide financial fallout from the 1929 Wall Street crash, and was abandoned during WWII German occupation of France.
The synthetic manufacture of metformin was revived post-war, and by 1957 it was available in Europe and Britain. Canada’s regulatory authority cleared it in 1972, but, also according to lore, it wasn’t until Squibb had obtained U.S. manufacturing rights that the FDA moved on it and cleared it in 1994 as a Type 2 drug. Metformin, and sulfonylureas such as Glucotrol, are still the mainstays for glucose control and improvement of insulin sensitivity in tissue, although there are other classes of drugs coming into wider use. Metformin is also believed to have a moderating effect on appetite, and users have reported success maintaining and even losing weight on the therapy. The FDA has yet, though, to enlarge its clearance of metformin beyond its existing label use: blood glucose control for people with Type 2 diabetes.
Despite metformin’s long history, scientists are still trying to pin down how exactly metformin works in the body. It’s long been assumed the drug works primarily in the bloodstream, but researchers have recently uncovered evidence that it may instead work primarily in the gut. Research on this continues.
Long term, uncontrolled Type 2 diabetes taxes muscle and organ tissue that is already nutritionally starving due to inefficient insulin production or insulin resistance in the body. The condition also taxes the pancreas to the point where it wears out and gives up making insulin, and makes the kidneys work harder to filter out excess glucose and waste. Advancing age can also tax the system by bringing on joint and tissue inflammation from reduced autoimmune response, weakened cellular structure, and even the inability of the body to replace dying cells with new ones.
The trial will involve biopsy sampling of muscle and body fat tissue of young healthy subjects for DNA comparison to tissue from older (60+ years ) subjects before and after metformin use, to see if a biological “fingerprint” of gene expression can be discerned. Favorable results could provide evidence that metformin works at a cellular level, opening up the possibility that it can be used as a brake on some naturally occurring aging conditions unrelated to diabetes.
To learn more about how to sign up for the trial, go to https://clinicaltrials.gov/ct2/show/NCT02432287.