Plate Nº 11 · recorded September 30, 2026
Health & Medicine ResearchReported finding
Amylin Drug Petrelintide Delivers Over 10% Weight Loss
Weekly injections of the amylin-based drug petrelintide produced over 10% weight loss with far less nausea and fewer gut side effects than GLP-1 drugs, a Phase II trial finds.
By Marcus Bennett4 min read749 words
In brief
- Petrelintide produced 10.2–10.7% average weight loss at higher doses over 42 weeks, versus 1.7% on placebo.
- Only 1.5% of participants discontinued petrelintide due to gastrointestinal side effects, compared with up to 75% one-year discontinuation rates for GLP-1 drugs in real-world data.
- Results come from a Phase II trial of 485 participants published in The Lancet Diabetes & Endocrinology; Phase III trials are still needed to confirm the findings.
An experimental obesity drug called petrelintide helped people lose more than 10% of their body weight with far fewer gastrointestinal side effects than current injectable weight-loss medications, according to results from a Phase II trial presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept. 28–Oct. 2) and published in The Lancet Diabetes & Endocrinology.
Participants who received weekly injections of petrelintide lost an average of 10.2% to 10.7% of their body weight over 42 weeks, depending on the dose. Those on placebo lost 1.7%. The trial, called ZUPREME 1, was led by professor Timothy Garvey of the University of Alabama at Birmingham.
That weight loss is somewhat smaller than what incretin-based drugs such as semaglutide (Ozempic, Wegovy) and tirzepatide typically achieve. But the tolerability advantage could matter enormously in practice. Real-world data suggest that up to 75% of people stop GLP-1 receptor agonist therapy within 12 months, often regaining weight and losing the drugs' cardiovascular benefits. Gastrointestinal problems are the leading reason for quitting — in one cardiovascular outcomes trial of semaglutide, roughly 37% of discontinuations were attributed to gut side effects.
In the petrelintide trial, only 1.5% of participants permanently stopped the drug because of gastrointestinal adverse events, and just 2.2% needed a dose reduction for that reason.
How the drug works
Petrelintide mimics amylin, a hormone made by the pancreas that helps regulate appetite. Amylin works through mechanisms that are partly independent of incretin pathways — the biological routes targeted by GLP-1 drugs. Both types of therapy activate pathways in the central nervous system that produce satiety, or feelings of fullness, but the study authors suggest amylin analogs may cause less activation of nausea and sickness pathways at effective doses. That difference in signaling could explain the gentler side-effect profile.
Several long-acting amylin analogs are in development for obesity, including cagrilintide, eloralintide and petrelintide.
What the trial found
The trial ran at 32 sites in the U.S., Poland and Romania. From Dec. 9, 2024, to Feb. 25, 2025, researchers screened 714 people and randomly assigned 485 to treatment. All participants received lifestyle counseling, including dietary guidance targeting a daily energy deficit of about 500 kcal and at least 150 minutes of moderate physical activity per week.
The average participant was 47 years old, weighed 107.1 kg (236 pounds) and had a BMI of 36.7. Slightly more than half (53%) were female.
Average weight loss at week 42 by dose: 8.7% on 1.0 mg, 9.2% on 2.5 mg, 10.7% on 5.0 mg, 10.5% on 7.0 mg and 10.2% on 9.0 mg. Beyond weight, petrelintide improved several cardiovascular risk factors, including blood pressure, C-reactive protein (a marker of systemic inflammation) and lipid levels such as cholesterol and triglycerides.
Nausea was the most common side effect, affecting 20% of petrelintide recipients versus 6% of the placebo group. Vomiting was infrequent — 3% with the drug versus 6% with placebo — and rates of diarrhea and constipation were similar in both groups. Serious adverse events occurred in 3% of treated participants and 4% of the placebo group, with no apparent link to dose. No deaths were reported.
The authors note that 88% to 98% of participants successfully escalated to the three highest maintenance doses, which all produced similar weight loss at week 42.
Cautions and next steps
These are Phase II results, meaning the drug still must pass larger, confirmatory Phase III trials before regulators can consider approval. The trial population was also 86% white, which may limit how broadly the findings apply.
"If reproduced in confirmatory Phase III trials, this therapy could be suitable for many individuals seeking double-digit percentage weight loss without significant, treatment-limiting gastrointestinal adverse events," the authors write.
In a linked comment, Dr. Sten Madsbad and Dr. Jens J. Holst of the University of Copenhagen point to a rationale for combining amylin and GLP-1 drugs, since their weight effects appear additive — an approach already being tested with cagrilintide plus semaglutide, and with dual-agonist molecules such as zenagamtide. But they flag an open question: whether combination therapy actually improves the side-effect profile, which was not evident in the cagrilintide-semaglutide trials.
For now, petrelintide's developers are moving forward into Phase III, positioning amylin-based therapy as a possible first-line long-term option — either alone or alongside existing incretin treatments.
via Medical Xpress (Source)
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