Adverse effect · Petrelintide

How common is GI side effects with Petrelintide?

C
Grade C — weak human evidence1 phase 2 RCT (n=485 dosed); phase 1 · effect size: small · adverse
Short answerWeak human evidence. 1 phase 2 RCT (n=485 dosed); phase 1: enough to be interesting, not enough to count on. Where an effect is seen it is a small effect. ZUPREME-1: nausea in 20% against 6% on placebo, described as predominantly mild and during dose escalation; vomiting 3% vs 6%, diarrhoea 7% vs 7%, constipation 7% vs 4%. No deaths. In the earlier phase 1 trial nausea occurred in 17–33% against 17% on placebo, and one participant stopped for gut symptoms. Whether the profile holds over 64 weeks in phase 3 is the open question.

What the studies show

ZUPREME-1: nausea in 20% against 6% on placebo, described as predominantly mild and during dose escalation; vomiting 3% vs 6%, diarrhoea 7% vs 7%, constipation 7% vs 4%. No deaths. In the earlier phase 1 trial nausea occurred in 17–33% against 17% on placebo, and one participant stopped for gut symptoms. Whether the profile holds over 64 weeks in phase 3 is the open question.

“The most common adverse event with petrelintide was nausea (79 [20%] of 404 participants vs five [6%] participants with placebo).”

Verbatim, from the abstractGarvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol, 2026 (online 29 Sep)

A few small or poorly-controlled human studies. Enough to be interesting; not enough to count on. Most of what gets called “clinically proven” online lives here.

  1. 1
    Garvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.Lancet Diabetes Endocrinol, 2026 (online 29 Sep)493 randomised, 485 dosed; 32 sites in Poland, Romania and the USA; 42 weeks, primary endpoint at 28 weeks. NCT06662539.
  2. 2
    Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.Diabetes Obes Metab, 2026Single- and multiple-ascending-dose trials; 16-week part in adults with overweight or obesity.

In context

Petrelintide is a once-weekly amylin receptor agonist developed by Zealand Pharma and partnered with Roche. In ZUPREME-1, a 493-person phase 2 trial published in September 2026, adults with obesity and no diabetes lost 7.9–9.8% of body weight at 28 weeks against 1.7% on placebo, and up to 10.7% by week 42. Nausea affected 20% against 6% on placebo; vomiting and diarrhoea were no more common than on placebo. A phase 3 programme of about 7,000 people began in September 2026. It is not approved anywhere.

Petrelintide is investigational (phase 3). Legal status differs by country — see the regulation section or the jurisdiction pages.

Questions

Is Petrelintide proven to cause GI side effects?
No. The human evidence is weak (1 phase 2 RCT (n=485 dosed); phase 1); LYO grades it C.
What studies are behind the grade?
ZUPREME-1: nausea in 20% against 6% on placebo, described as predominantly mild and during dose escalation; vomiting 3% vs 6%, diarrhoea 7% vs 7%, constipation 7% vs 4%. No deaths. In the earlier phase 1 trial nausea occurred in 17–33% against 17% on placebo, and one participant stopped for gut symptoms. Whether the profile holds over 64 weeks in phase 3 is the open question.
Is Petrelintide approved for this?
No. Petrelintide is investigational (phase 3); it is not an approved medicine for any indication in the jurisdictions LYO covers.

Other outcomes for Petrelintide

Written and maintained by LYO Research — how pages are written and checked. Reviewed 7 October 2026. Grades count human evidence only; see how LYO grades. Not medical advice. Correct this page →