GLP-1 Alternative Shows ‘Meaningful’ Weight Loss With Less Nausea and Vomiting

An experimental drug called petrelintide that offers “clinically meaningful” weight loss with relatively few stomach issues is making its way through the research pipeline.

Findings from a phase 2 study on petrelintide were presented today at an American Diabetes Association (ADA) conference.

What the New Research Found About Petrelintide’s Effectiveness and Side Effects

The latest research, a phase 2 trial, involved nearly 500 participants who were overweight or had obesity (the average BMI was 37, the average age was 47, and just over half were female).

Researchers noted that people receiving the medication experienced “statistically significant and clinically meaningful” weight loss starting at 28 weeks.

“This is safe, moderate weight loss that I think most of our patients with obesity require,” said lead study author W. Timothy Garvey, MD, professor of nutrition science at the University of Alabama at Birmingham and director of the UAB Diabetes Research Center, while presenting the research at the diabetes conference.

There were no cases of vomiting and no treatment discontinuations because of gastrointestinal issues, even among participants receiving the maximum effective dose.

“Why should patients have to feel sick to their stomachs for the privilege of having their disease treated? That’s the question I keep asking myself,” Dr. Garvey said. “We need to do something; we’ve got to figure this out.”

How Do Amylin-Based Drugs Like Petrelintide Work?

Similar to GLP-1, amylin is a hormone that helps regulate energy consumption by signaling to the brain that the body is full and does not need to eat more, leading to reduced meal size and food intake, according to Wayne Ho, MD, a clinical investigator in diabetes and obesity and a professor at Keck School of Medicine in Los Angeles.

“Amylin [like GLP-1] slows down gastric emptying, further adding to the ‘fullness’ effect,” says Dr. Ho, who is also a spokesperson for the Obesity Society.

Ashley Koff, RD, a registered dietitian based in Oregon, and the founder of the Better Nutrition program, adds that amylin addresses the reward area of the brain, lessening the dopamine hit you get from eating sugar and fat.

“It will be interesting to see if people [taking amylin drugs] end up having fewer sweet cravings than with other drugs,” she says.

Comparing Amylin Meds and GLP-1s

Because amylin-based therapies may be better tolerated than GLP-1s, some pharmaceutical companies believe these drugs will provide an attractive alternative for patients with obesity, diabetes, or both conditions.

On the other hand, much of the research data so far suggests that amylin drugs don’t produce as much weight loss as certain GLP-1s. 

Addressing that comparison, Garvey said, “A lot of patients don’t require 25 to 30 percent weight loss. It’s not safe for them, they don’t feel good, and there’s a higher risk of malnutrition and changing body composition [such as muscle loss] that may be deleterious in some.“

How much weight a person may lose using an amylin medication is not so certain, suggests Dr. Ho. He cites research showing that the amylin-based experimental drug eloralintide can lead to 20 percent total body weight loss at the highest dose when used alone. He also points to late-phase trials showing up to 22.7 percent weight loss when a different amylin-based drug in development (cagrilintide) is used in combination with a GLP-1 (semaglutide).

On the whole, these developments involving amylin are good news for patient choice. “It is an exciting time for obesity research,” says Ho.

Amylin-Targeting Drugs May Be the Next Wave in Obesity and Diabetes Treatment

While GLP-1 medications currently dominate the weight loss and diabetes markets, several major pharmaceutical companies in addition to Roche and Zealand are now working to develop drugs that mimic amylin.

This amylin-based medication has been around for some time; it was approved two decades ago as an add-on therapy to treat patients with diabetes who use insulin but cannot achieve desired blood sugar levels. Doctors can prescribe pramlintide off label for weight loss, but it is not officially approved for this use.

“This is my opinion, based on the data we have at hand, so it’s a little bit hypothetical — I think these amylin medications could emerge as a first-line treatment for obesity,“ Garvey said.