Update Note: This article reports new information involving the experimental weight-loss drug petrelintide following MedicalDaily's earlier coverage. The newest data come from the peer-reviewed trial paper published September 29, 2026, in The Lancet Diabetes & Endocrinology and presented at the EASD annual meeting in Milan on September 30, 2026.
Full, peer-reviewed results for petrelintide, an experimental once-weekly amylin injection, show that adults with excess weight lost between 8.7% and 10.7% of their body weight over 42 weeks, compared with 1.7% on placebo. Nausea was reported by 20% of people on the drug vs. 6% on placebo. The findings were published in The Lancet Diabetes & Endocrinology.
The drug is not approved anywhere, and it is not available by prescription. It is being developed by Danish drugmaker Zealand Pharma with Roche, and Zealand sponsored the trial.
For the many people who stopped Wegovy, Ozempic, or Zepbound because of stomach side effects, the paper answers a narrower question than earlier headlines did. It shows what the dose-by-dose data look like, where the benefit levels off, and how long the wait for a real option may still be.
Dose by Dose, the Numbers Behind the Results
The ZUPREME-1 trial randomly assigned 485 adults without type 2 diabetes at 32 sites in the U.S., Poland, and Romania. Participants had an average body mass index of 36.7 and received one of five doses or placebo, along with lifestyle counseling. Average weight loss was 8.7% at 1.0 mg, 9.2% at 2.5 mg, 10.7% at 5.0 mg, 10.5% at 7.0 mg, and 10.2% at 9.0 mg, according to a summary released through EASD.
The pattern matters. The three highest doses produced nearly identical results, which suggests the benefit levels off near 10% at this stage of treatment. Between 88% and 98% of participants reached their target dose.
The headline figures reflect people who stayed on treatment. Counting everyone, including those who stopped, average weight loss was up to 10.2% vs. 1.4% on placebo, Investing.com reported from the company's release.
Most other side effects were uncommon. Vomiting occurred in 3% of treated participants vs. 6% on placebo, and diarrhea affected 7% of both groups. Only 1.5% stopped treatment because of stomach side effects, and 2.2% needed a lower dose. Serious adverse events were reported in 3% of the petrelintide group and 4% of the placebo group, with no deaths.
Amylin Works Differently From Ozempic and Zepbound
Amylin is a hormone the pancreas releases along with insulin after meals, and it helps signal fullness. GLP-1 drugs such as semaglutide act on a separate appetite pathway. One hypothesis is that amylin drugs may cause less nausea at effective doses, but that idea has not been proven.
"This is a well-tolerated medication," lead investigator Dr. Timothy Garvey of the University of Alabama at Birmingham told HCPLive in June. Approved GLP-1 drugs have produced larger average weight loss in their own trials, but Garvey said "This current level of 10-15% is sufficient to treat a large number of patients who have obesity."HCPLive noted that Garvey reports financial ties to several drugmakers, including Zealand.
In a commentary published with the paper, University of Copenhagen researchers Dr. Sten Madsbad and Dr. Jens J. Holst wrote that "amylin-based therapies might have a future as individual as well as combination therapies." They cautioned that combination products have not yet clearly shown fewer side effects than GLP-1 drugs alone.
From Conference Abstract to Peer-Reviewed Paper
MedicalDaily previously reported on early petrelintide results presented at the American Diabetes Association meeting in June, when the focus was its tolerability compared with GLP-1 drugs. That report relied on conference data that had not been through full peer review.
What is new is the complete, reviewed dataset, including per-dose weight loss, dose-reduction rates, and serious side effects. Zealand has also started three global Phase 3 trials for chronic weight management. Together, they plan to enroll about 7,000 people, including people with type 2 diabetes and people with established heart disease.
MedicalDaily Evidence Check: This was a randomized, placebo-controlled Phase 2 trial of 485 adults, funded by the manufacturer. It found meaningful weight loss with low rates of vomiting and dropouts. It did not compare petrelintide directly with semaglutide or tirzepatide, and it did not measure heart attacks, strokes, or long-term safety.
Limits of the Evidence and the Road Ahead
The trial ran 42 weeks, excluded people with type 2 diabetes, and enrolled a population that was 86% white. Results may differ for older adults, people with diabetes, and more diverse groups. A companion trial in people with type 2 diabetes, ZUPREME-2, is expected to report topline results in the second half of 2026, according to Zealand's petrelintide pipeline page.
No price, approval date, or insurance coverage exists yet. Phase 3 trials typically take years, so petrelintide is unlikely to reach pharmacies soon. Zealand and Roche also plan a Phase 2 trial pairing petrelintide with Roche's experimental drug enicepatide, reflecting a wider industry bet on amylin combinations.
Cost will matter as much as tolerability. Insurance coverage for today's weight-loss drugs remains uneven, and any new option would face the same fights over price and prior authorization, a practical barrier for the patients most likely to want an alternative.
People struggling with GLP-1 side effects should talk with their clinician about dose adjustments or other approved medicines rather than seeking unapproved amylin products sold online, which may be counterfeit or unsafe. Do not stop or change a prescribed medication without medical guidance.
Petrelintide produced roughly 10% weight loss with low rates of vomiting and treatment dropouts, but it remains experimental, and Phase 3 results will decide whether it becomes a real choice.
Key Questions Answered
What is petrelintide? It is an experimental once-weekly amylin injection for obesity developed by Zealand Pharma and Roche. It is not approved.
How much weight did people lose? Average loss ranged from 8.7% to 10.7% over 42 weeks, vs. 1.7% on placebo.
What were the side effects? Nausea affected 20% of treated participants vs. 6% on placebo. Vomiting and diarrhea rates were similar to or lower than placebo.
Is it better than Ozempic or Zepbound? There was no head-to-head comparison. Approved GLP-1 drugs have shown larger average weight loss in their own trials.
When could it be available? Not soon. Three Phase 3 trials are underway, and no approval timeline has been announced.
Who paid for the study? Zealand Pharma sponsored the trial, and the lead investigator reports ties to several drugmakers.
Published by Medicaldaily.com
