New Class Of Weight-Loss Drugs May Have Fewer Side Effects Than GLP-1s

MONDAY, Oct. 5, 2026 (HealthDay News) — An emerging class of weight-loss medications helps users shed pounds but with a much lower risk for gastrointestinal side effects compared to popular GLP-1s, researchers report.

The weekly injected medications are called amylin-based obesity drugs. They work off a hormone that the pancreas secretes during eating. Much like GLP-1 medications, amylin-based meds help suppress appetite.

In the new international trial, people taking one such drug, called petrelintide, lost an average of 10% of their starting weight over 42 weeks, compared to people taking a placebo. 

That's a lower average weight loss than is typically seen with GLP-1 medicines, but the plus was that most users avoided the gastrointestinal side effects that are common with GLP-1s, researchers said.

"If reproduced in confirmatory phase 3 trials, this therapy could be suitable for many individuals seeking double-digit percentage weight loss without significant, treatment-limiting, gastrointestinal adverse events," said a team led by Dr. Timothy Garvey, professor of medicine at the University of Alabama at Birmingham.

Two other amylin-based weight-loss drugs, cagrilintide and eloralintide, are also in development, the researchers noted.

Garvey presented the findings Wednesday at the European Association for the Study of Diabetes meeting in Milan. The study was published simultaneously in The Lancet Diabetes and Endocrinology.

The trial was funded by Zealand Pharma, which makes petrelintide.

The study was conducted at 32 centers in Poland, Romania and the United States. All 485 participants were living with obesity and received counseling on weight loss through diet and at least 150 minutes per week of exercise. 

A total of 404 of the participants also received weekly petrelintide injections, in doses ranging from 1 to 9 milligrams. Another 81 of the participants received a "dummy" placebo injection. 

Over the 42 weeks of the trial, people on petrelintide lost about 10% of their starting weight, with weight loss ranging from 8.7% on the 1 milligram dose to 10.5% on the 7 milligram dose, according to the researchers.

The incidence of gastrointestinal side effects was low. The most common side effect was nausea, experienced by 20% of people taking petrelintide and 6% of those taking placebo.  

Among petrelintide users, 3% experienced vomiting, 7% experienced diarrhea (equal to those taking placebo), and 7% experienced constipation (compared to 4% among those taking placebo).

Nearly all participants could tolerate the drug, the authors noted.

“The vast majority of participants (88 to 98%) were able to successfully escalate to the three highest maintenance doses evaluated, all of which produced similar weight loss at week 42," Garvey's team wrote. "The tolerability profile of petrelintide was further supported by the low proportion of participants who permanently discontinued petrelintide due to gastrointestinal adverse events — 1.5% — as well as the small percentage who required dose reduction for this reason: 2.2%.”

Why are amylin-based drugs better tolerated than GLP-1s? 

The researchers think that although both weight loss meds bring on a feeling of fullness, they may affect "signaling" within the body's central nervous system in different ways, especially when it comes to gastrointestinal function.

Garvey's team thinks amylin-based meds may have an edge over GLP-1s, since fewer side effects will allow folks to maintain therapy longer. 

In a linked journal commentary, two University of Copenhagen experts, Dr. Sten Madsbad and Dr. Jens Holst, said amylin-based drugs might also be used in combination with GLP-1s.

“The partly complementary mechanisms of amylin and GLP-1 receptor agonism also provide a rationale for combination therapy, in which the weight effects of the individual components seem to be additive," they wrote. 

"Amylin-based therapies might have a future as individual as well as combination therapies," the two experts said.

More information

Find out more about currently approved weight loss medications at the Cleveland Clinic.

SOURCE: European Association for the Study of Diabetes, news release, Sept. 29, 2026