Weight-loss and diabetes injections such as Wegovy and Ozempic (both semaglutide) may have wider medical benefits than we first thought, after work in mice suggests they act on the brain to lessen body-wide inflammation.
The finding could explain why this class of drugs seems to reduce heart attacks more than would be expected from their weight-loss effects alone.
It also lends support to their use in combating a wider range of health conditions that involve inflammation, including Alzheimer’s disease and Parkinson’s disease, which is being investigated in trials.
Semaglutide works by mimicking a gut hormone called GLP-1. Normally released after eating, GLP-1 lowers appetite, makes people feel full and triggers the release of insulin, a hormone involved in blood sugar regulation.
Several studies have suggested that, as well as causing people to lose weight, semaglutide lowers inflammation, which is a mild rise in certain kinds of immune system activity. For instance, semaglutide lowers the level of a compound in the blood called C-reactive protein (CRP), an established sign of inflammation, says Daniel Drucker at the University of Toronto in Canada.
A growing body of work suggests that inflammation is involved in numerous conditions that hadn’t previously been linked to the immune system, including heart disease and Alzheimer’s disease, although this has yet to be translated into new treatments for clinical use.
Obesity is also linked with inflammation, so the effect of semaglutide on CRP could just be a side effect of people losing weight, rather than the drug itself reducing inflammation.
To find out, Drucker and his colleagues investigated how several GLP-1 mimics affect inflammation in mice. First, they injected bacteria from the gut into the animals’ abdomens, causing them to have a bacterial infection of the blood. This leads to a strong immune response, raising inflammation.
In some mice, they also injected a GLP-1 mimic, either semaglutide or another member of this drug class called exenatide.
The GLP-1 mimics reduced the animals’ inflammatory response to the infection, but this failed to happen when the researchers used mice that had been genetically modified so they lacked the receptor for GLP-1 on their brain cells.
The reduction of inflammation also failed to happen if the experiment was done using genetically normal mice that had a compound that blocks the GLP-1 receptor injected into their brains.
Together, these results show that GLP-1 mimics such as Ozempic reduce inflammation by acting on brain cells, and it isn’t just a side effect of weight loss.
“Weight loss is good, but you don’t need to have the weight loss to have the benefits,” says Drucker. For instance, in a recent randomised trial of Wegovy, the drug started preventing heart attacks within the first few months, before people would have lost much weight, he says.
“It was a known effect of these drugs, that they act on inflammation,” says Ivan Koychev at the University of Oxford. “This paper is helpful because it’s clarifying the underlying mechanism.”
In theory, medicines that dampen inflammation could cause people to get more infections, although this hasn’t been observed so far in people having the injections for weight loss or diabetes, says Koychev.