Petrelintide vs Eloralintide: Amylin Analogue Phase 2 Data Compared

Petrelintide vs eloralintide is the comparison researchers are now making between the two newest long-acting amylin analogues to report Phase 2 obesity data: Zealand Pharma and Roche's petrelintide (ZUPREME-1, NCT06662539) and Eli Lilly's eloralintide (NCT06230523). Both are once-weekly subcutaneous peptides that act on amylin receptors rather than the GLP-1 pathway, but their published results, trial durations and development stages differ in ways that make direct efficacy comparison unreliable.

Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.

Quick Answer: In Phase 2 trials, petrelintide produced up to 10.7% mean weight reduction at 42 weeks versus 1.7% with placebo, while eloralintide produced up to 20% at 48 weeks versus 0.4% with placebo; the trials differ in duration, doses and design, so the figures are not head-to-head evidence.

TL;DR:

• Petrelintide (Zealand Pharma/Roche) reported ZUPREME-1 topline data on March 5, 2026: up to 10.7% weight loss at week 42 versus 1.7% placebo.
• Eloralintide (Eli Lilly) reported a 48-week Phase 2 trial in The Lancet: 9% to 20% weight loss across dose arms versus 0.4% placebo.
• Both are selective amylin-pathway peptides given once weekly by subcutaneous injection; neither is FDA approved.
• Eloralintide already has multiple Phase 3 trials registered, while petrelintide is being prepared for Phase 3 registrational trials.
• Petrelintide has no PubMed-indexed record in this library yet, so its figures below rely on sponsor announcements and trial registry data.

Why amylin analogues are being compared

Amylin is a peptide co-secreted with insulin from pancreatic beta cells, and its receptors are heteromeric complexes of the calcitonin receptor and receptor activity-modifying proteins. Research interest in amylin analogues has grown because they engage satiety pathways that are distinct from those targeted by semaglutide and tirzepatide. Long-acting amylin analogues are being studied both as standalone agents and as partners for incretin-based compounds.

The best-characterised late-stage amylin analogue is cagrilintide, studied mainly as part of the cagrilintide plus semaglutide combination in the REDEFINE program. Eloralintide and petrelintide are the two newer entrants that have reported Phase 2 monotherapy data, which is why researchers tracking the field now read them side by side. The eloralintide vs cagrilintide comparison covers the older pairing in detail.

Petrelintide: mechanism and evidence base

Petrelintide is a long-acting amylin analogue developed by Zealand Pharma. Roche entered an exclusive collaboration and licensing agreement for the compound in March 2025. Zealand and Roche describe it as designed for once-weekly subcutaneous dosing and for tolerability, which is the attribute the sponsors emphasise most in their announcements.

ZUPREME-1 (NCT06662539) was a randomized, double-blind, placebo-controlled, dose-finding Phase 2 trial in adults with overweight or obesity without type 2 diabetes. According to the March 5, 2026 topline announcement, 493 participants were randomized to one of five once-weekly doses or placebo. Doses were escalated in four-week steps for up to 16 weeks, followed by maintenance through week 42. A later sponsor report of the published analysis describes 485 participants, doses from 1.0 mg to 9.0 mg, and a mean baseline BMI of about 36.7 kg/m2; the difference from the topline count likely reflects the analysis population, though the sponsor materials reviewed do not state this explicitly.

Reported efficacy was up to 10.7% mean body weight reduction at week 42 versus 1.7% with placebo (p<0.001). Secondary measures reported by the sponsor included waist circumference, C-reactive protein and triglycerides, all moving further with petrelintide than with placebo. On tolerability, the sponsor reported that at the maximally effective dose there were no vomiting events and no discontinuations due to gastrointestinal adverse events, with nausea reported more often than with placebo across the pooled treated group.

Trial-registry and sponsor data are the only sources used here. A peer-reviewed report in The Lancet Diabetes & Endocrinology was announced by the sponsor on September 29, 2026 (presented at EASD on September 30); because no PubMed record for it is held in this library at the time of writing, no PMID is cited for petrelintide. Treat the petrelintide figures as sponsor-reported until the full paper is indexed. Full results for the second Phase 2b trial, ZUPREME-2 in people with type 2 diabetes, were still pending in the announcements reviewed.

Eloralintide: mechanism and evidence base

Eloralintide (LY3841136) is a selective amylin receptor agonist developed by Eli Lilly. Its full profile is at /library/eloralintide/. The Phase 2 trial published in The Lancet in December 2025 (PMID 41207310; NCT06230523) randomized 263 adults with obesity or overweight and at least one weight-related comorbidity, without type 2 diabetes, to six dose or titration arms (1 mg, 3 mg, 6 mg, 9 mg, 6-9 mg, 3-9 mg) or placebo for 48 weeks.

Mean body weight reduction ranged from 9% at the lowest dose to 20% at the 9 mg and 6-9 mg arms, versus 0.4% with placebo, with no clear plateau at the higher doses. The most common adverse events were nausea and fatigue, generally dose-dependent. Registered Phase 3 studies include NCT07282600 in type 2 diabetes, NCT07369011 in obstructive sleep apnea with obesity, NCT07215559 combining eloralintide with the GIP-receptor agonist macupatide, and NCT07392190 (ENLIGHTEN-6), an add-on study to an existing weekly incretin.

Side-by-side comparison

Reading the efficacy gap carefully

The gap between 10.7% and 20% should not be read as a like-for-like ranking. The trials ran for different lengths (42 versus 48 weeks), tested different dose ranges and titration schedules, and enrolled different populations. Eloralintide's higher-dose arms showed no clear plateau at 48 weeks, while the petrelintide sponsors have framed their program around tolerability as well as magnitude. A meaningful comparison would require either a head-to-head study or matched analyses of individual-level data, and neither exists.

Researchers comparing the two therefore tend to separate the questions: how much weight reduction each compound has produced under its own trial conditions, and how the gastrointestinal adverse-event profiles compare. On the second question the evidence is thinner for both, because the petrelintide tolerability figures come from sponsor summaries and the eloralintide paper reports dose-dependent nausea without a direct comparator.

Differential research applications

Studies of amylin analogues have addressed several distinct questions: monotherapy activity, additive effects with incretin compounds, and add-on use after weight-loss plateaus on incretin therapy. Eloralintide's registered Phase 3 program covers combination and add-on designs, so it is the more common reference point for those questions. Petrelintide's published record is currently monotherapy in people without type 2 diabetes, with the type 2 diabetes trial still to report.

Two free tools may help when tracking these programs. The trial tracker lists registered studies by compound and phase, and the half-life chart puts the pharmacokinetic profiles of long-acting peptides in one view. Petrelintide's half-life is not stated in the sources reviewed for this article, so it is not tabulated here.

Regulatory and compounding status

Neither compound holds approval from the FDA or EMA. Both are investigational, and neither is eligible for 503A compounding as an investigational biologic peptide. The nearest late-stage benchmark is the cagrilintide plus semaglutide combination, for which the sponsor reported a regulatory submission in December 2025; see the cagrilintide profile for its current status. Timelines for petrelintide Phase 3 starts and ZUPREME-2 results are sponsor projections and may change.

Cited studies

• PMID 41207310, "Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial" (The Lancet, 2025). https://doi.org/10.1016/S0140-6736(25)02155-5
• PMID 40544433, "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)" (New England Journal of Medicine, 2025). https://doi.org/10.1056/NEJMoa2502081
• PMID 39626360: "Subcutaneous amycretin versus semaglutide 2.4 mg in adults with overweight or obesity: a randomised, double-blind, double-dummy, phase 1b/2 trial" (The Lancet, 2024). https://doi.org/10.1016/S0140-6736(24)02496-8
• NCT06662539 (ZUPREME-1), ClinicalTrials.gov registry record for petrelintide.
• Roche press release, March 5, 2026, "Roche announces positive Phase II results for petrelintide": https://www.roche.com/media/releases/med-cor-2026-03-05
• Zealand Pharma announcement, September 29-30, 2026, EASD 2026 presentation and Lancet Diabetes & Endocrinology publication of ZUPREME-1 (sponsor-reported; no PMID confirmed at time of writing).

Frequently asked questions

Q: What is the difference between petrelintide and eloralintide?

A: Both are once-weekly subcutaneous amylin-pathway peptides, but petrelintide is developed by Zealand Pharma and Roche while eloralintide is developed by Eli Lilly. Their Phase 2 trials differed in length, dose range and size, so the reported weight-loss figures are not directly comparable.

Q: How much weight loss did petrelintide show in ZUPREME-1?

A: The sponsors reported up to 10.7% mean body weight reduction at week 42 versus 1.7% with placebo in the Phase 2 trial (NCT06662539). These figures come from sponsor announcements, with the Lancet Diabetes & Endocrinology report announced on September 29, 2026.

Q: Is petrelintide FDA approved?

A: No. Petrelintide is investigational, and the sponsors have described plans for Phase 3 registrational trials. Any timelines for those trials are sponsor projections.

Q: Does eloralintide act on the GLP-1 receptor?

A: No. Eloralintide is a selective amylin receptor agonist that acts independently of the GLP-1 pathway used by semaglutide and tirzepatide. Its Phase 3 program also studies it alongside incretin-pathway compounds.

Q: Why is there no PMID for petrelintide on this page?

A: The peer-reviewed report was announced by the sponsor on September 29, 2026 (presented at EASD on September 30), and no PubMed record was available in this library at the time of writing. The page cites the ClinicalTrials.gov identifier and sponsor documents instead, and will be updated when the paper is indexed.

See also:

• Eloralintide vs cagrilintide: comparing the next generation of amylin analogs: the established amylin pairing that frames this comparison
• Cagrilintide vs semaglutide: amylin-GLP-1 combination vs GLP-1 monotherapy: REDEFINE 1 data for the amylin benchmark
• Amycretin vs semaglutide: a unimolecular GLP-1/amylin agonist from a third developer

For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.