A treatment can help weight change and still be difficult to live with. I want future options to leave room for eating well, moving and enjoying life, so tolerability interests me as much as the headline percentage.
Petrelintide brings that question into the amylin conversation. It does not settle it yet.
What is new?
ZUPREME-1 has now been published in The Lancet Diabetes & Endocrinology, alongside EASD reporting on 29–30 September 2026. This is the same Phase 2 trial discussed at the June ADA meeting, not a second independent study. [1] [2] [4]
It compared five doses of petrelintide, a long-acting amylin analogue, with placebo in people with obesity or overweight without type 2 diabetes. There were 485 people who received a dose, 53% women; the sponsor separately reports 493 enrolled. Treatment was assigned by chance and kept unknown to participants and researchers. [2] [3] [5]
What happened to weight?
At 42 weeks, the greatest average reduction was 10.7%, compared with 1.7% on placebo, in the analysis estimating continued treatment. The analysis allowing for people stopping treatment gave 10.2% versus 1.4%. [2]
Those are two ways of looking at the same trial. The main planned assessment was at 28 weeks; the 42-week headline was an additional outcome.
Does “gentler” tell us enough?
The sponsor reports no vomiting or stopping because of stomach and bowel adverse events in the maximally effective 5 mg group. That is encouraging for that particular group, not a promise for every dose or person. [2] [3]
Across petrelintide groups, the EASD summary reported nausea in about 20% versus 6% with placebo, vomiting in 3% versus 6%, diarrhoea in 7% versus 7%, and constipation in 7% versus 4%. The earlier ADA abstract reported 1.5% stopping petrelintide because of stomach and bowel adverse events. [3] [4]
So “similar to placebo” should not make the differences disappear. And because there was no active GLP-1 comparison, we cannot say this trial proves petrelintide is easier to tolerate than tirzepatide or semaglutide, the active ingredient in Ozempic and Wegovy.
What else would I want to know?
The sponsor reported reductions of up to 10.8 cm in waist measurement, 41% in hsCRP, an inflammation marker, and 21% in triglycerides, a type of blood fat. Placebo changes were 4.3 cm, 6% and 9%. These are selected changes in measurements, not proof of fewer heart attacks or longer life. Zealand funded the trial, and Phase 3 has begun. [2] [3]
The peer-reviewed publication strengthens this Phase 2 evidence. It does not settle long-term safety, comparisons with other medicines or menopause outcomes. Including women does not itself show that they respond differently.
And although nourishment and muscle matter to the questions I am asking, this trial does not establish improved nutrition or muscle preservation. I want those outcomes measured directly.
Read the sources
Publication status and results were checked against the sponsor, EASD research summary and earlier trial abstract. The journal’s full text was not accessible during this update.
- Garvey and colleagues: ZUPREME-1 ↗The Lancet Diabetes & Endocrinology · DOI 10.1016/S2213-8587(26)00213-5 · Peer-reviewed trial.
- Zealand: publication and additional ZUPREME-1 findings ↗Release dated 30 September 2026, distributed 29 September US time · Sponsor account.
- EASD: research-team summary of ZUPREME-1 ↗29 September 2026 · Trial population and adverse-event reporting.
- Garvey and colleagues: ADA ZUPREME-1 abstract ↗5 June 2026 · Earlier conference abstract from the same trial, not an additional study.
- Zealand: petrelintide trial programme ↗Sponsor pipeline page · Confirms ZUPREME-1 studied people without type 2 diabetes.