Semaglutide and tirzepatide work by mimicking the action of GLP-1, a hormone found naturally in the body. These drugs act on GLP-1 receptors in the pancreas to trigger the release of insulin after eating, which helps control blood sugar levels in people with diabetes. They also bind to GLP-1 receptors in the brain to make people feel full, leading them to eat less.
Scientists are still trying to understand the other knock-on effects of these drugs, including the cardiovascular benefits. One explanation is that GLP-1 receptors also exist on cells in the heart, blood vessels, liver, and kidney, so these drugs may act directly on these organs. “It turns out that these receptors are present in many parts of the body,” says Katherine Tuttle, a clinical professor of nephrology at the University of Washington School of Medicine.
A recent trial led by Tuttle was stopped early due to overwhelming evidence that semaglutide has protective effects on the kidney. The study included more than 3,500 people with both type 2 diabetes and kidney disease. About half of the participants took a weekly injection of semaglutide while the other half got a placebo shot. After an average of three and a half years, the semaglutide group had a 24 percent lower likelihood of having a major kidney disease event—such as needing dialysis or a kidney transplant.
Clinical trials aren’t usually designed to determine the mechanism of a drug—and in fact, the mechanisms of many drugs on the market aren’t entirely known. But Tuttle has her own theory for how semaglutide is protecting the kidney: by shutting down inflammation.
GLP-1 drugs may even calm inflammation in the brain, raising hope that they could be used to treat conditions like dementia and Parkinson’s disease. Inflammation is thought to play a role in the development of both conditions.
In a UK trial of 200 people with mild Alzheimer’s disease, an older GLP-1 drug called liraglutide appeared to slow shrinking of the parts of the brain that control memory, learning, language, and decisionmaking by as much as 50 percent. Those who received weekly injections of liraglutide over 52 weeks also had an 18 percent slower decline in cognitive function after a year compared to those who got the placebo. Obesity is a known risk factor for developing Alzheimer’s disease, but the study didn’t specifically include people with obesity, which suggests that the drug is helping through another means.
The authors, who presented the findings last month at the Alzheimer’s Association annual conference, think liraglutide could be working in a few different ways—including reducing inflammation in the brain and lowering insulin resistance.
Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association, says the results are exciting, although larger trials will be needed to confirm this protective effect. “This is really the first study where we’ve seen a hint of this benefit for individuals,” she says.
And the neuroprotective effects may extend to Parkinson’s disease as well. An older diabetes drug in the GLP-1 family, lixisenatide, seemed to slow the progression of Parkinson’s symptoms in a small study of 156 patients in France. In results published in April, participants with early-stage Parkinson’s who took the drug for a year saw no worsening of motor symptoms such as tremors, balance problems, slowness, and stiffness. Those who received a placebo, meanwhile, experienced a decline over the same period.
