Experimental Weight-Loss Drug Petrelintide Shows Promise With Fewer Stomach Side Effects
A new type of obesity medication could eventually offer patients another option for significant weight loss without some of the gastrointestinal problems commonly associated with GLP-1 drugs.
Researchers studying the experimental drug petrelintide found that people receiving weekly injections lost roughly 10% of their starting body weight during a 42-week clinical trial. At the same time, relatively few participants stopped treatment because of nausea, vomiting, diarrhea or other gastrointestinal side effects.
Petrelintide belongs to an emerging category of medications based on amylin, a hormone naturally released by the pancreas in response to eating. Amylin plays a role in appetite and satiety, helping signal to the brain that the body has had enough food.
That makes the hormone an increasingly interesting target for obesity researchers looking beyond GLP-1 medications.
Nearly 500 People Participated in the Trial
The international study enrolled 485 adults living with obesity at 32 clinical sites in the United States, Poland and Romania.
All participants received counseling designed to support weight loss through diet and at least 150 minutes of physical activity each week.
Researchers assigned 404 participants to receive weekly injections of petrelintide at doses ranging from 1 milligram to 9 milligrams. Another 81 participants received placebo injections.
After 42 weeks, average weight loss among people receiving petrelintide was approximately 10% of starting body weight.
Results varied somewhat according to dose. Participants receiving the 1-milligram dose lost an average of 8.7% of their starting weight, while those receiving the 7-milligram dose lost approximately 10.5%.
Those numbers do not reach the weight-loss levels reported with some of today’s GLP-1-based obesity treatments. Petrelintide, however, could have another potential advantage: tolerability.
Gastrointestinal Side Effects Were Relatively Limited
Nausea was the most frequently reported gastrointestinal side effect, occurring in 20% of participants receiving petrelintide compared with 6% of those receiving placebo.
Vomiting occurred in 3% of petrelintide users. Diarrhea was reported by 7%, the same percentage seen in the placebo group. Constipation occurred in 7% of people receiving petrelintide compared with 4% receiving placebo.
Importantly, only 1.5% of participants permanently stopped petrelintide treatment because of gastrointestinal side effects. Another 2.2% required a dose reduction for gastrointestinal problems.
Researchers also reported that between 88% and 98% of participants were able to increase their dosage to the three highest maintenance doses studied.
Those findings could be important because gastrointestinal side effects can make long-term obesity treatment difficult for some patients.
Dr. Timothy Garvey, professor of medicine at the University of Alabama at Birmingham and lead researcher on the study, said the results will need to be confirmed in larger Phase 3 trials. If they are, petrelintide could potentially become an option for people seeking double-digit percentage weight loss while minimizing treatment-limiting gastrointestinal problems.
How Petrelintide Differs From GLP-1 Drugs
Both amylin-based treatments and GLP-1 receptor agonists can reduce appetite and increase feelings of fullness, but researchers believe the two drug classes may influence signaling within the central nervous system differently.
Those differences could help explain why amylin-based medications appear to produce fewer gastrointestinal problems.
The distinction could also make amylin drugs useful alongside GLP-1 therapies rather than simply as competitors.
Researchers noted that the biological mechanisms involved in amylin and GLP-1 signaling appear to complement one another. Combining the two approaches could potentially produce greater weight loss than either medication alone.
That possibility is already drawing considerable attention as pharmaceutical companies investigate the next generation of obesity treatments.
More Amylin-Based Weight-Loss Drugs Are Coming
Petrelintide is not the only amylin-based obesity drug currently under development.
Cagrilintide and eloralintide are also being studied as potential weight-management treatments. The growing pipeline suggests amylin could become an important new target in obesity medicine, either as a stand-alone treatment or as part of combination therapies.
For petrelintide specifically, the next major question will be whether larger and longer Phase 3 studies can reproduce the weight-loss results while maintaining the favorable tolerability seen in this trial.
The study was funded by Zealand Pharma, the company developing petrelintide.
Results were presented at the European Association for the Study of Diabetes meeting in Milan and simultaneously published in The Lancet Diabetes & Endocrinology.
If subsequent trials confirm the findings, petrelintide could occupy a different position in the rapidly expanding obesity-drug market: potentially offering somewhat less weight loss than the most powerful GLP-1 therapies, but with a side-effect profile that some patients may find easier to tolerate.