New Class of Weight-Loss Drugs Shows Promise Beyond Appetite Suppression

A new generation of injectable weight-loss drugs, based on amylin hormones, is showing promising results in clinical trials, offering a potential alternative for individuals seeking to manage weight with fewer side effects than current GLP-1-based medications.

These amylin-based compounds mimic the effects of amylin, a peptide hormone that helps regulate appetite by signaling satiety to the brain and slowing stomach emptying. Unlike GLP-1s, which target different receptors, amylins may offer a complementary mechanism with a potentially lower incidence of gastrointestinal issues such as nausea and vomiting, which lead approximately 40% of patients to discontinue GLP-1 treatments within a year.

At the European Association for the Study of Diabetes (EASD) meeting in Milan, researchers presented data on several experimental amylin-based drugs.

Novo Nordisk reported on CagriSema, a weekly injectable combining semaglutide (the active ingredient in Wegovy and Ozempic) with cagrilintide, an amylin analog. In trials, CagriSema led to a 22.4% reduction in body weight among overweight or obese participants after one year, compared to a placebo. The drug also influenced brain responses to food, potentially reducing food-related preoccupations, and in patients with Type 2 diabetes, it reduced harmful fat in the liver and pancreas.

Eli Lilly presented findings on EloraTZP, a combination of its amylin analog eloralintide and tirzepatide (the active ingredient in Zepbound). This weekly injectable helped overweight or obese participants with Type 2 diabetes lose 23% of their body weight, compared to 14.8% for those using tirzepatide alone. The combination also improved A1C levels more effectively than either component on its own.

Zealand Pharmaceuticals shared results from its study of petrelintide, an amylin-based weekly injectable that resulted in an average 10% body weight loss in overweight or obese individuals without diabetes. Participants on the drug reported side effect rates similar to those on placebo.

These amylin-based medications are being explored as a potential first-line therapy due to their efficacy and improved side-effect profiles. Dr. Timothy Garvey, who led the petrelintide trial, noted that while some nausea can occur, it is at less than half the rate seen in GLP-1 trials. He suggested that amylins could provide a valuable, better-tolerated option for primary care physicians looking to individualize weight management treatments.

Novo Nordisk has submitted CagriSema for U.S. Food and Drug Administration approval for treating overweight and obesity in non-diabetic individuals, with a decision expected by year-end. While other amylin-based drugs are in earlier stages of development, their experimental success suggests they may soon join GLP-1s as a significant class of weight-loss medications.