{ "checked": "2026-10-26", "page": "https://jabbitapp.com/research/amylin-weight-loss-drugs-petrelintide-eloralintide-cagrilintide-teardown.html", "registry": { "petrelintide": { "query": "ClinicalTrials.gov API v2, query.intr=petrelintide", "records": 9, "phase_counts": { "PHASE1": 3, "PHASE2": 3, "PHASE3": 3 }, "selected": { "NCT06662539": { "acronym": "ZUPREME", "phase": [ "PHASE2" ], "status": "COMPLETED", "enrollment": 493, "enrollment_type": "ACTUAL", "sponsor": "Zealand Pharma", "start": "2024-12-09", "primary_completion": "2025-09-30", "first_posted": "2024-10-29", "primary_outcome_timeframe": "From Baseline (Day 1) to Week 28", "has_results": false }, "NCT06926842": { "acronym": null, "phase": [ "PHASE2" ], "status": "COMPLETED", "enrollment": 221, "enrollment_type": "ACTUAL", "sponsor": "Zealand Pharma", "start": "2025-04-22", "primary_completion": "2026-08-13", "first_posted": "2025-04-15", "primary_outcome_timeframe": "From Baseline (Day 1) to Weeks 28", "has_results": 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A/S", "start": "2025-11-05", "primary_completion": "2027-05-11", "first_posted": "2025-10-24", "primary_outcome_timeframe": "From baseline (week 0) to end of treatment (week 64)", "has_results": false }, "NCT07220759": { "acronym": "RENEW 2", "phase": [ "PHASE3" ], "status": "ACTIVE_NOT_RECRUITING", "enrollment": 330, "enrollment_type": "ESTIMATED", "sponsor": "Novo Nordisk A/S", "start": "2025-11-05", "primary_completion": "2027-05-12", "first_posted": "2025-10-24", "primary_outcome_timeframe": "From baseline (week 0) to end of treatment (week 64)", "has_results": false }, "NCT07745504": { "acronym": "RENEW 4", "phase": [ "PHASE3" ], "status": "RECRUITING", "enrollment": 285, "enrollment_type": "ESTIMATED", "sponsor": "Novo Nordisk A/S", "start": "2026-08-04", "primary_completion": "2027-05-18", "first_posted": "2026-08-04", "primary_outcome_timeframe": "From baseline (week 0) to end of treatment (week 26)", "has_results": false } } } }, "weight_loss_best_arm_vs_placebo": [ { "trial": "Petrelintide · ZUPREME 1 · 28 wk", "drug_pct": 9.8, "placebo_pct": 1.7, "estimand": "efficacy estimand", "status": "Peer reviewed", "ref": "zup1" }, { "trial": "Petrelintide · ZUPREME-2 (type 2 diabetes) · 28 wk", "drug_pct": 9.2, "placebo_pct": 2.0, "estimand": "efficacy estimand", "status": "Company topline", "ref": "zup2pr" }, { "trial": "Eloralintide · phase 2 · 48 wk", "drug_pct": 20.0, "placebo_pct": 0.4, "estimand": "efficacy estimand", "status": "Peer reviewed", "ref": "elo2" }, { "trial": "Eloralintide alone (type 2 diabetes) · 48 wk", "drug_pct": 12.3, "placebo_pct": 3.0, "estimand": "efficacy estimand", "status": "Company topline", "ref": "eloratzp" }, { "trial": "Cagrilintide · phase 2 · 26 wk", "drug_pct": 10.8, "placebo_pct": 3.0, "estimand": "trial product estimand", "status": "Peer reviewed", "ref": "cagri2" }, { "trial": "Cagrilintide alone · REDEFINE 1 · 68 wk", "drug_pct": 11.5, "placebo_pct": 3.0, "estimand": "treatment policy estimand", "status": "Peer reviewed", "ref": "redef1" }, { "trial": "CagriSema · REDEFINE 1 · 68 wk", "drug_pct": 20.4, "placebo_pct": 3.0, "estimand": "treatment policy estimand", "status": "Peer reviewed", "ref": "redef1" }, { "trial": "Wegovy · STEP 1 · 68 wk", "drug_pct": 14.9, "placebo_pct": 2.4, "estimand": "treatment policy estimand", "status": "Peer reviewed", "ref": "step1" }, { "trial": "Zepbound · SURMOUNT-1 · 72 wk", "drug_pct": 20.9, "placebo_pct": 3.1, "estimand": "treatment regimen estimand", "status": "Peer reviewed", "ref": "surm1" } ], "nausea_drug_vs_placebo": [ { "trial": "Petrelintide, ZUPREME 1 (all arms pooled)", "drug": "20%", "placebo": "6%", "ref": "zup1" }, { "trial": "Eloralintide, phase 2 (range across arms)", "drug": "11%-64%", "placebo": "14%", "ref": "elo2" }, { "trial": "Cagrilintide, phase 2 (range across arms)", "drug": "20%-47%", "placebo": "18%", "ref": "cagri2" }, { "trial": "Wegovy, label pool", "drug": "44%", "placebo": "16%", "ref": "wegovy" }, { "trial": "Zepbound, label pool (range across doses)", "drug": "25%-29%", "placebo": "8%", "ref": "zepbound" }, { "trial": "Pramlintide (Symlin), type 1 diabetes label pool", "drug": "48%", "placebo": "17%", "ref": "symlin" } ], "abstract_quotes": { "42810355": { "title": "Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial", "journal": "Lancet Diabetes Endocrinol", "year": "2026", "quotes": [ "493 were randomly assigned and 485 received at least one dose", "The primary endpoint was percentage change in bodyweight from baseline after 28 weeks.", "versus -1·7% (-2·8 to -0·5) with placebo", "Bodyweight continued to decline to week 42, with reductions of up to -10·7% with petrelintide.", "The most common adverse event with petrelintide was nausea (79 [20%] of 404 participants vs five [6%] participants with placebo).", "Vomiting was infrequent with petrelintide (12 [3%] participants vs five [6%] with placebo)", "No deaths were reported.", "had similar gastrointestinal tolerability to that of placebo apart from predominantly mild nausea during dose escalation", "Zealand Pharma." ] }, "42017294": { "title": "Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials", "journal": "Diabetes Obes Metab", "year": "2026", "quotes": [ "had a half-life of ~10 days", "reduced body weight by up to 8.6% after 16 weeks", "with no serious or severe treatment-emergent adverse events (TEAEs)" ] }, "41207310": { "title": "Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial", "journal": "Lancet", "year": "2025", "quotes": [ "We enrolled 263 participants from 46 research centres in the USA.", "for 48 weeks", "compared with -0·4% (-2·2 to 1·4) in the placebo group", "The most common adverse events with eloralintide were nausea", "and fatigue", "Eli Lilly." ] }, "41559929": { "title": "Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept", "journal": "Diabetes Obes Metab", "year": "2026", "quotes": [ "100 participants", "the least squares mean percent reduction in body weight across the dose groups ranged from 2.6% to 11.3%", "Gastrointestinal adverse events, including diarrhoea (10% of participants), nausea (8%), and vomiting (4%), were infrequent in those receiving eloralintide." ] }, "34798060": { "title": "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial", "journal": "Lancet", "year": "2021", "quotes": [ "we randomly assigned 706 participants to cagrilintide", "versus placebo (3·0% [3·3 kg]", "The trial had a 26-week treatment period", "More participants receiving cagrilintide 0·3-4·5 mg had gastrointestinal adverse events compared with placebo (41%-63% vs 32%), primarily nausea (20%-47% vs 18%).", "Novo Nordisk A/S." ] }, "40544433": { "title": "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity", "journal": "N Engl J Med", "year": "2025", "quotes": [ "A total of 3417 participants underwent randomization", "was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo", "Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group)", "Funded by Novo Nordisk" ] }, "33567185": { "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity", "journal": "N Engl J Med", "year": "2021", "quotes": [ "we enrolled 1961 adults", "was -14.9% in the semaglutide group as compared with -2.4% with placebo", "discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%])", "Funded by Novo Nordisk" ] }, "35658024": { "title": "Tirzepatide Once Weekly for the Treatment of Obesity", "journal": "N Engl J Med", "year": "2022", "quotes": [ "we assigned 2539 adults", "-3.1% (95% CI, -4.3 to -1.9) with placebo", "Supported by Eli Lilly" ] }, "42452898": { "title": "Amylin Analogs: The Next Major Class of Weight Loss Therapy: A Review of Experimental Data and Early-Phase Clinical Trials", "journal": "Diabetes Obes Metab", "year": "2026", "quotes": [ "Pramlintide, the first approved amylin analogue, established proof of concept but was limited by modest efficacy and frequent dosing.", "slows gastric emptying, suppresses glucagon secretion, and promotes meal termination through central mechanisms" ] }, "42586227": { "title": "Beyond GLP-1: Amylin-based pharmacotherapy and the search for better-tolerated weight-loss drugs", "journal": "Pharmacol Res", "year": "2026", "quotes": [ "calcitonin receptor engagement, exposure kinetics, and downstream neural circuit recruitment may influence whether reduced food intake reflects physiological satiation or aversive signaling" ] } }, "press_release_quotes": { "zealand_zupreme2": [ "Petrelintide achieved up to 9.2% mean body weight reduction at week 28 versus 2.0% with placebo", "Very low discontinuation rates due to gastrointestinal adverse events (1.9% for petrelintide versus 1.7% in placebo group)", "in 220 people living with overweight or obesity and type 2 diabetes", "(range across treatment arms: 7.4-9.2%)", "At week 28, petrelintide demonstrated a HbA1c reduction of up to 0.65% versus an increase of 0.23% with placebo", "No unexpected safety signals were observed with petrelintide treatment.", "The full trial results from ZUPREME-2 are expected to be presented at an upcoming scientific conference." ], "zealand_zupreme1": [ "The treatment discontinuation rate due to adverse events (AEs) was 4.8% with petrelintide in the maximally effective treatment arm versus 4.9% with placebo.", "Notably, female participants lost considerably more weight than male participants in this trial." ], "zealand_ph3": [ "The three trials are expected to enroll approximately 7,000 participants in total.", "The primary endpoint in the Phase 3 ZUPREME trials is percentage change in body weight from baseline to week 64.", "In 2025, Zealand Pharma and Roche entered into an exclusive collaboration and licensing agreement" ], "lilly_elora_ph2": [ "The most common adverse events were mild to moderate gastrointestinal symptoms and fatigue, which were seen more frequently in the higher dose arms." ], "lilly_eloratzp": [ "Treatment discontinuation rates due to adverse events were 10.8% to 27.0% with EloraTZP, 0% to 10.8% with eloralintide, 2.9% with tirzepatide and 16.7% with placebo.", "Eloralintide is already being evaluated as a single agent in Phase 3 trials for the treatment of obesity.", "Eloralintide alone reduced body weight by up to an average of 28.6 lbs (12.3%)", "in 367 adults with obesity or overweight and type 2 diabetes" ], "novo_easd": [ "A decision is expected in Q4 2026.", "CagriSema is a fixed-dose combination of a long-acting amylin receptor agonist, cagrilintide, and a GLP-1 receptor agonist, semaglutide." ] }, "conflict_statements": { "42810355": "Zealand Pharma", "42017294": "Zealand Pharma A/S has sponsored the trials described in this manuscript and funded the preparation of the manuscript.", "41559929": "are employees and stockholders of Eli Lilly and Company, USA.", "34798060": "are employees and shareholders at Novo Nordisk A/S.", "42810353": "SM has served on advisory boards for Novo Nordisk" }, "labels": { "symlin": { "source": "openFDA drug label, SymlinPen (pramlintide), AstraZeneca, set id 4aea30ff-eb0d-45c1-b114-3127966328ff, version 18, effective 2019-12-18", "quotes": [ "SYMLIN use with insulin increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes.", "SYMLIN is indicated as an adjunctive treatment in patients with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy.", "nausea, vomiting, anorexia, headache" ] }, "wegovy": "FDA label 215256s025 (revised 06/2026): nausea 44% vs 16% placebo; 6.8% vs 3.2% stopped for adverse reactions", "zepbound": "FDA label 217806s042: nausea 25-29% vs 8% placebo; 4.8-6.7% vs 3.4% stopped for adverse reactions" }, "optum": "Optum Rx Notable New Drugs report, fall 2026: CagriSema expected FDA decision December 18, 2026", "analysis": { "note": "Jabbit analysis. Cross-trial comparisons are rough: trials differ in length, population, escalation and estimand, and the best arm is shown. Amylin drugs alone (petrelintide, cagrilintide) have produced roughly 9-12% weight loss in phase 2 and 3 trials of 26-68 weeks, below Wegovy and Zepbound in their pivotal trials; eloralintide's best phase 2 arm reached about 20% at 48 weeks in 263 people. Nausea is still the most common side effect; petrelintide's rates look lower than GLP-1 labels but trials are not head to head. No amylin drug is approved for weight loss; CagriSema (cagrilintide plus semaglutide) has an FDA decision expected in Q4 2026 per Novo. Stand-alone phase 3 readouts per registry estimates: cagrilintide RENEW 1/2 around May 2027, eloralintide ENLIGHTEN from January 2028, petrelintide ZUPREME-3/4 in late 2028." } }