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 side effects of these drugs, including cardiovascular benefits. One explanation is that GLP-1 receptors also exist on cells in the heart, blood vessels, liver and kidneys, 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 Washington University School of Medicine.
TO recent trial The clinical trial led by Tuttle was stopped early because of overwhelming evidence that semaglutide has protective effects on the kidney. The study included more than 3,500 people with type 2 diabetes and kidney disease. About half of the participants received a weekly injection 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 suffer a major kidney disease event, such as needing dialysis or a kidney transplant.
Clinical trials are not typically designed to determine a drug’s mechanism of action, and in fact the mechanisms of action of many drugs on the market are not fully understood. But Tuttle has his own theory about how semaglutide protects the kidney: by suppressing inflammation.
GLP-1 drugs can even calm inflammation in the brain, raising hopes that they could be used to treat diseases such as dementia and Parkinson’s disease. Inflammation is thought to play a role in the development of both diseases.
In a U.K. trial of 200 people with mild Alzheimer’s disease, an older GLP-1 drug called liraglutide appeared to slow the shrinkage of parts of the brain that control memory, learning, language and decision-making by as much as 50 percent. Those 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 the placebo. Obesity is a known risk factor for developing Alzheimer’s disease, but the study did not specifically include obese people, suggesting the drug is helping through other means.
The authors, who presented the findings last month At the Alzheimer’s Association’s annual conference, they believe liraglutide could work in several ways, including reducing inflammation in the brain and decreasing insulin resistance.
Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association, says the results are encouraging, 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 people,” she says.
And the neuroprotective effects may extend to Parkinson’s disease as well. An older diabetes drug from the GLP-1 family, lixisenatide, appeared to slow the progression of Parkinson’s symptoms in a small study of 156 patients in France. The results published in AprilParticipants with early-stage Parkinson’s who took the drug for a year did not experience any worsening of motor symptoms, such as tremors, balance problems, slowness and stiffness. In contrast, those who received a placebo experienced deterioration over the same period.
