New Weight-Loss Drug Petrelintide Achieves Over 10% Weight Loss at Higher Doses with Far Fewer Side Effects than GLP-1s
A phase 2 trial published in The Lancet Diabetes & Endocrinology found that petrelintide, an amylin-based weekly injection for obesity, produced weight loss ranging from 8.7% to 10.7% across five dose levels over 42 weeks, with the three highest doses each exceeding 10%, while causing far fewer gastrointestinal side effects than GLP-1 drugs such as semaglutide and tirzepatide.
An international phase 2 clinical trial has found that petrelintide, a new amylin-based obesity drug given as a weekly injection, produced weight loss of between 8.7% and 10.7% of body weight over 42 weeks depending on dose, with the three highest doses each exceeding 10%. The trial enrolled 485 participants with obesity across 32 sites in the United States, Poland, and Romania, testing five dose levels from 1.0 mg to 9.0 mg weekly alongside standardised lifestyle counselling. The placebo group lost an average of 1.7% of body weight.
Amylin is a pancreatic hormone that helps regulate appetite through mechanisms partly independent of the incretin pathway used by GLP-1 drugs such as semaglutide and tirzepatide. Because petrelintide works differently, its gastrointestinal side-effect burden was notably lower: only 1.5% of petrelintide-treated participants permanently discontinued the drug due to gastrointestinal adverse events, compared with roughly 37% of GLP-1 discontinuations attributed to gastrointestinal side effects in a cardiovascular outcomes trial of semaglutide. Nausea was the most common adverse event (20% with petrelintide vs 6% with placebo), while rates of vomiting, diarrhoea, and constipation were low and broadly similar between the active and placebo groups. No deaths were reported.
The findings were presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan and published in The Lancet Diabetes & Endocrinology. The study's authors, including Professor Timothy Garvey of the University of Alabama at Birmingham, say petrelintide could become a first-line option for long-term weight management — either as an alternative to or in combination with GLP-1-based therapies — if results are confirmed in phase 3 trials. The study was funded by Zealand Pharma.
