Semaglutide and tirzepatide work by mimicking the effects of GLP-1, a hormone that occurs naturally in the body. These drugs work 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 other side effects of these drugs, including cardiovascular benefits. One explanation is that GLP-1 receptors are also found on cells in the heart, blood vessels, liver and kidneys, so these drugs may act directly on those 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.
AND recent trial led by Tuttle was stopped early because of overwhelming evidence that semaglutide had a protective effect on the kidneys. The study involved more than 3,500 people with type 2 diabetes and kidney disease. About half of the participants received weekly injections of semaglutide, while the other half received a placebo injection. After an average of three and a half years, the semaglutide group was 24 percent less likely to have a sedate kidney-related event — such as needing dialysis or a kidney transplant.
Clinical trials aren’t typically designed to determine a drug’s mechanism of action—and in fact, the mechanisms of action of many drugs on the market aren’t fully understood. But Tuttle has his own theory about how semaglutide protects the kidneys: by inhibiting inflammation.
GLP-1 drugs can even reduce inflammation in the brain, raising hopes that they could be used to treat conditions like dementia and Parkinson’s disease, both of which are thought to play a role in inflammation.
In a U.K. study of 200 people with subtle Alzheimer’s, an older GLP-1 drug called liraglutide seemed to snail-paced the shrinkage of parts of the brain that control memory, learning, language and decision-making by up to 50 percent. People who received weekly injections of liraglutide for 52 weeks also had an 18 percent slower decline in cognitive function after a year, compared with those who received a placebo. Obesity is a known risk factor for developing Alzheimer’s, but the study did not specifically include people with obesity, suggesting that the drug helps in other ways.
Authors who presented the results last month at the Alzheimer’s Association’s annual conference, it is believed that liraglutide may work in several 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 stimulating, although larger studies 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 neuroprotective effects may extend to Parkinson’s disease. An older GLP-1 diabetes drug, lixisenatide, seemed to snail-paced the progression of Parkinson’s disease symptoms in a miniature study of 156 patients in France. The results published in AprilParticipants with early-stage Parkinson’s disease who took the drug for a year saw no worsening of motor symptoms, such as tremors, balance problems, slowness and stiffness. Meanwhile, those who received a placebo experienced a worsening over the same period.