Petrelintide

Petrelintide (ZP8396) Phase 1 Single Ascending Dose Trial

First-in-human, randomised, double-blind, placebo-controlled single ascending dose (SAD) trial of petrelintide (ZP8396). Subcutaneous doses of 0.04-2.4 mg and a 0.35 mg intravenous dose were evaluated in adults with normal weight or overweight. Petrelintide was well tolerated with no serious or severe treatment-emergent adverse events; gastrointestinal events were mostly mild. NCT number per Synapse trial index (ADA 2023/2026 abstracts); registry title and dates not retrieved this run. Published together with the MAD trial in Diabetes, Obesity and Metabolism (2026; PMID 42017294).

Petrelintide (ZP8396) Phase 1 Multiple Ascending Dose Trial

Randomised, double-blind, placebo-controlled multiple ascending dose (MAD) trial. Part 1 evaluated 6 once-weekly subcutaneous doses of 0.6 and 1.2 mg; Part 2 evaluated 16 once-weekly doses escalated every 2 weeks to target doses of 2.4, 4.8 and 9.0 mg in adults with overweight or obesity. Petrelintide had a half-life of ~10 days, showed steady-state dose proportionality and reduced body weight by up to 8.6% after 16 weeks. Nausea occurred in 16.7%-33.3% of petrelintide recipients vs 16.7% on placebo in Part 2; one participant discontinued for GI adverse events. Published in Diabetes, Obesity and Metabolism (2026; PMID 42017294).

Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity (ZUPREME-1)

ZUPREME-1 is a randomised, double-blind, placebo-controlled, dose-finding Phase 2 trial at 32 sites (USA, Poland, Romania) in adults with BMI ≥30 kg/m² or ≥27 kg/m² with hypertension and/or dyslipidaemia, without type 2 diabetes. Participants were randomised 5:1 to one of five once-weekly subcutaneous petrelintide doses (1.0-9.0 mg, escalated in 4-week steps over up to 16 weeks) or placebo through week 42. Mean body weight reduction at week 42 was up to 10.7% vs 1.7% with placebo (efficacy estimand; up to 10.2% vs 1.4% by treatment-policy estimand). Waist circumference fell up to 10.8 cm vs 4.3 cm and hsCRP up to 41% vs 6%. GI adverse events were generally mild and similar to placebo; at the maximally effective dose there was no vomiting and no GI-related discontinuation. Topline results announced by Roche/Zealand March 5, 2026; presented at ADA and EASD 2026 and published in The Lancet Diabetes & Endocrinology (September 2026).

Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2)

ZUPREME-2 was a randomised, double-blind, placebo-controlled, US-based Phase 2b trial of three once-weekly subcutaneous petrelintide doses (escalated every 4 weeks) vs placebo in 220 adults with overweight or obesity and type 2 diabetes on metformin ± an SGLT2 inhibitor (mean baseline BMI 36.3 kg/m², HbA1c 8.0%). Topline results (Zealand Pharma, October 7, 2026): the primary endpoint was met in all arms, with mean weight loss of 7.4%-9.2% at week 28 vs 2.0% with placebo (efficacy estimand; largely consistent under the treatment-regimen estimand). HbA1c fell by up to 0.65% vs a 0.23% rise with placebo (placebo-adjusted -0.61% to -0.88%). Discontinuations due to GI adverse events were 1.9% vs 1.7% with placebo; GI events were mostly mild and occurred during escalation. No unexpected safety signals. Full results to be presented at an upcoming scientific conference.

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Once Weekly Petrelintide vs. Placebo in Participants With Overweight or Obesity (ZUPREME-3)

Registrational Phase 3a trial (ZUPREME-3) of once-weekly petrelintide versus placebo in ~3,900 adults with overweight (BMI ≥27 to <30 kg/m²) with at least one weight-related comorbidity or obesity (BMI ≥30 kg/m²), without type 2 diabetes. Design: 12-week dose escalation, maintenance to week 64, safety follow-up to week 77, optional open-label extension. Primary endpoint: percentage change in body weight from baseline to week 64. Zealand Pharma announced initiation of the ZUPREME Phase 3a program on September 22, 2026 (registry listed status NOT_YET_RECRUITING at time of entry; trial name mapped from population description).

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Once Weekly Petrelintide vs. Placebo in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME-4)

Registrational Phase 3a trial (ZUPREME-4) of once-weekly petrelintide versus placebo in ~600 adults with overweight or obesity and type 2 diabetes. Design mirrors ZUPREME-3: 12-week dose escalation, maintenance to week 64, safety follow-up to week 77, optional open-label extension. Primary endpoint: percentage change in body weight from baseline to week 64. Part of the ZUPREME Phase 3a program initiated September 22, 2026 (trial name mapped from population description).

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Efficacy and Safety of Petrelintide Co-Administered With RO7795068 in Adults With Obesity or Overweight

Roche-sponsored Phase 2 dose-finding trial evaluating Zealand Pharma/Roche's long-acting amylin analogue petrelintide co-administered with Roche's signal-biased dual GLP-1/GIP receptor agonist enicepatide (RO7795068, CT-388) versus placebo in adults with obesity or overweight. Zealand Pharma stated (September 22, 2026) that the combination Phase 2 trial is planned for initiation in the second half of 2026. Registry status and title per trial-registry index as of 2026-09-29; enrollment target not yet confirmed.