While we consider metformin to be a weight neutral diabetes medication, in clinical practice we see that some people do seem to lose weight when they start using it. While this could certainly be related to changes in lifestyle with receiving education about diabetes, a recent study sheds light on how some people may enjoy some weight loss with metformin.
Published in the journal Nature, this fascinating paper discusses a peptide hormone called GDF15, which is produced in the human intestine, and reduces appetite in the (hind)brain. The authors found that after 2 weeks of metformin, there was a 2.5x increase in GDF15 levels. In another study, they also found that after 18 months of treatment with metformin, where participants lost about 3.5% weight on average, GDF15 levels were higher in the metformin group than in placebo, and the change in GDF15 levels was modestly correlated with weight loss. They also found that the effect of metformin to reduce blood sugar was independent of GDF15.
Despite being available for decades, we are still learning more about metformin. In addition to its effect to reduce insulin resistance, metformin also increases GLP1 levels (a hormone that our intestines make that talks to our pancreas to control blood sugars, and acts as a satiety (fullness) signal in our brain, thereby reducing appetite). Metformin also alters the bacteria in our gut (microbiome) which may have a beneficial impact on metabolic syndrome as well.
BOTTOM LINE: GDF15 is added to the list of intestinal hormones that act as satiety (fullness) signals in our brains. Metformin increases GDF15 in some people, which may be why we see weight loss in some people when they start metformin. The effects of metformin to lower blood sugar is not related to GDF15, so people who don’t have an increase in GDF15 will still enjoy a reduction in insulin resistance and improvement in blood sugars by other mechanisms.
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