{"id":"petrelintide","name":"Petrelintide","aliases":["ZP8396","long-acting amylin analogue","Zealand/Roche amylin"],"url":"https://lyoresearch.com/compounds/petrelintide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"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.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 phase 2 RCT (n=493) and 2 phase 1 RCTs published; phase 3 running","regulatory_status":"Investigational (phase 3)","molecule":{"formula":"C185H305N49O61","molecular_weight":"4192","cas":null,"pubchem_cid":172915807,"note":"No CAS number listed on the PubChem record"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 10 days (phase 1)","licensed_regimen":null,"product":null,"source":{"title":"Olsen MB, et al. Petrelintide phase 1 trials. Diabetes Obes Metab 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/"}},"outcomes":[{"outcome":"Body weight","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"1 phase 2 RCT (n=493, 42 wk); phase 1","evidence":"ZUPREME-1, published in The Lancet Diabetes & Endocrinology on 29 September 2026: 493 adults with obesity, or overweight with hypertension or dyslipidaemia, and no type 2 diabetes were randomised 5:1 to one of five weekly doses or placebo. At 28 weeks, the primary endpoint, weight had fallen 7.9–9.8% against 1.7% on placebo; by week 42 the largest loss was 10.7%. Efficacy estimand, so participants who stopped are not fully counted. The earlier phase 1 trial saw up to 8.6% at 16 weeks and measured a half-life of about ten days.","references":[{"citation":"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.","where":"Lancet Diabetes Endocrinol, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"},{"citation":"Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/"}],"verbatim":{"text":"Mean percentage change in bodyweight from baseline after 28 weeks (efficacy estimand) was -7·9% (95% CI -9·0 to -6·7) with petrelintide 1·0 mg, -7·9% (-9·0 to -6·7) with petrelintide 2·5 mg, -9·8% (-10·9 to -8·6) with petrelintide 5·0 mg, -9·3% (-10·5 to -8·2) with petrelintide 7·0 mg, and -9·4% (-10·5 to -8·3) with petrelintide 9·0 mg versus -1·7% (-2·8 to -0·5) with placebo.","citation":"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.","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"}},{"outcome":"GI side effects","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"1 phase 2 RCT (n=485 dosed); phase 1","evidence":"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.","references":[{"citation":"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.","where":"Lancet Diabetes Endocrinol, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"},{"citation":"Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/"}],"verbatim":{"text":"The most common adverse event with petrelintide was nausea (79 [20%] of 404 participants vs five [6%] participants with placebo).","citation":"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.","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational."},{"region":"United States","status":"Not approved","note":"Investigational; phase 3 running since September 2026. Products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"How much weight do people lose on petrelintide?","a":"7.9–9.8% at 28 weeks across five doses in the published phase 2 trial, against 1.7% on placebo, and up to 10.7% by week 42. Those figures come from one dose-finding trial; phase 3 will give the 64-week number."},{"q":"Is petrelintide better tolerated than semaglutide?","a":"In its phase 2 trial nausea affected 20% of participants and vomiting 3%, with diarrhoea no more common than on placebo. No trial has compared it directly with semaglutide, and the weight loss was smaller too. Treat the tolerability advantage as a hypothesis that phase 3 has to confirm."}],"references":[{"cite":"Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/","note":"Single- and multiple-ascending-dose trials; 16-week part in adults with overweight or obesity."},{"cite":"Genentech / Zealand Pharma. Positive phase II results for petrelintide (ZUPREME-1).","where":"Press release, 5 Mar 2026","url":"https://www.businesswire.com/news/home/20260305198579/en/Genentech-Announces-Positive-Phase-II-Results-for-Petrelintide-an-Amylin-Analog-Developed-for-People-Living-With-Overweight-and-Obesity","note":"Topline only; not peer-reviewed."},{"cite":"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.","where":"Lancet Diabetes Endocrinol, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/","note":"493 randomised, 485 dosed; 32 sites in Poland, Romania and the USA; 42 weeks, primary endpoint at 28 weeks. NCT06662539."},{"cite":"Zealand Pharma. Initiation of the registrational phase 3 ZUPREME programme of petrelintide in people with overweight or obesity.","where":"Press release No. 17/2026, 22 Sep 2026","url":"https://www.globenewswire.com/news-release/2026/09/22/3366613/0/en/zealand-pharma-announces-initiation-of-the-registrational-phase-3-zupreme-program-of-petrelintide-in-people-with-overweight-or-obesity.html","note":"ZUPREME-3, -4 and -5; about 7,000 participants; primary endpoint percentage change in body weight at week 64."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"ZUPREME-1 phase 2 published (Lancet Diabetes Endocrinol, 29 Sep 2026): weight and side-effect rows now rest on the paper, with new verbatim results replacing the phase 1 sentences; phase 3 start (22 Sep 2026) recorded. Grade held at C for stage."},{"date":"2026-09-23","note":"Initial publication from the phase 1 paper. Grade C for stage."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}