Amylin Agonists 2026: CagriSema, Petrelintide, Eloralintide

What are amylin agonists, and which ones reported data in 2026?

Amylin agonists are peptides that activate the receptors for amylin, a 37-amino-acid hormone that pancreatic beta cells release together with insulin. Amylin receptors are built from the calcitonin receptor paired with a receptor activity-modifying protein (RAMP), and amylin signaling has been studied for its effects on satiety, gastric emptying, and post-meal glucagon release. That is a different receptor system from the GLP-1, GIP, and glucagon receptors targeted by semaglutide, tirzepatide, and retatrutide.

In September 2026 three amylin-based programs reported new human data: Novo Nordisk's CagriSema (cagrilintide plus semaglutide), Zealand Pharma's petrelintide, and Eli Lilly's eloralintide, alone and combined with tirzepatide as EloraTZP. None of these compounds is FDA-approved as of October 19, 2026. Every figure below comes from a company release, a peer-reviewed paper, or a ClinicalTrials.gov record, and each is labeled with its source and date.

How do the amylin programs compare?

The cagrilintide compound profile lists the full cagrilintide trial registry, and the cagrilintide and amylin biology article covers the earlier phase 1 and phase 2 work.

What did REIMAGINE 5 report on September 21, 2026?

REIMAGINE 5 (NCT06534411) is a Phase 3 trial comparing once-weekly CagriSema 1.0 mg/1.0 mg with tirzepatide 5 mg in adults with type 2 diabetes whose glucose was not controlled on metformin, an SGLT2 inhibitor, or both. Novo Nordisk's topline release on September 21, 2026 reported, at week 60:

Source: Novo Nordisk company announcement, September 21, 2026. Weight figures use the efficacy estimand.

The same release reported REDEFINE 9, a 68-week Phase 3 trial in adults with overweight or obesity, where CagriSema 1.0 mg/1.0 mg produced a mean body weight change of -21.0% against -2.0% with placebo. Novo described CagriSema as well tolerated in both trials, with a safety profile consistent with previous studies. These are topline figures; neither trial had been published in a peer-reviewed journal at the time of the release, and the registry record for REIMAGINE 5 lists no posted results.

When is the FDA expected to decide on CagriSema?

Novo Nordisk states that it filed a New Drug Application with the U.S. FDA for CagriSema for weight management in December 2025 and that it expects a decision in the fourth quarter of 2026. Until a decision is announced, CagriSema remains investigational. Cagrilintide on its own is a separate development track: the RENEW 1 (NCT07220642) and RENEW 2 (NCT07220759) Phase 3 trials are listed as active, not recruiting, and RENEW 4 (NCT07745504) is recruiting.

What did the petrelintide phase 2 trial report?

ZUPREME 1 (NCT06662539) was published online in The Lancet Diabetes & Endocrinology on September 29, 2026 (PMID 42810355). The trial ran at 32 sites in Poland, Romania, and the USA and enrolled adults without type 2 diabetes with a BMI of at least 30, or at least 27 with hypertension or dyslipidaemia. Participants were randomized 5:1 to once-weekly petrelintide at one of five maintenance levels (1.0 to 9.0 mg) or placebo for 42 weeks, including dose escalation. Of 493 randomized, 485 received study drug. The primary endpoint was body weight change at 28 weeks.

Source: Garvey et al., Lancet Diabetes Endocrinol 2026 (PMID 42810355), efficacy estimand.

Body weight continued to decline after the primary endpoint, with reductions of up to 10.7% at week 42. Nausea was the most common adverse event, in 20% of petrelintide participants against 6% on placebo. Vomiting occurred in 3% against 6%, diarrhoea in 7% against 7%, and constipation in 7% against 4%. No deaths were reported. The trial was funded by Zealand Pharma. The Phase 3 trials ZUPREME-3 (NCT07843498), ZUPREME-4 (NCT07843485), and ZUPREME-5 (NCT07843472) are recruiting, with Hoffmann-La Roche listed as lead sponsor.

The 28-week phase 2 figures are not directly comparable with the 60-week and 68-week CagriSema figures or the 80-week retatrutide figures: populations, durations, comparators, and estimands all differ.

What did Lilly present on eloralintide and EloraTZP at EASD 2026?

Eloralintide (formerly LY3841136) is described by Lilly as an investigational once-weekly, selective amylin receptor agonist. EloraTZP is eloralintide combined with tirzepatide, a GIP and GLP-1 receptor agonist. Lilly's September 15, 2026 release listed two EASD 2026 presentations:

• Phase 1 (oral presentation): in adults with obesity or overweight, eloralintide 3 mg added to tirzepatide 5 mg produced a 17% mean body weight reduction over 16 weeks, against 10% with tirzepatide 5 mg alone (efficacy estimand).
• Phase 2 ([NCT06603571](https://clinicaltrials.gov/study/NCT06603571)): eloralintide and tirzepatide, alone or combined, in adults with obesity or overweight and type 2 diabetes. The registry lists the study as completed with 367 participants. Results were presented at an EASD symposium on amylin on September 30, 2026; the September 15 release did not include figures, and they are not reported here.

Eloralintide Phase 3 trials are recruiting, including ENLIGHTEN-1 (NCT07321886) in obesity or overweight without type 2 diabetes and ENLIGHTEN-2 (NCT07282600) with type 2 diabetes. EloraTZP Phase 3 trials AMPLIFY-1 (NCT07881432) and AMPLIFY-2 (NCT07881458) are registered and not yet recruiting.

What is still unknown?

Three things remain open as of October 19, 2026. The FDA decision on CagriSema is expected but not announced. The REIMAGINE 5 and REDEFINE 9 results are topline only, pending full publication. And the EloraTZP phase 2 figures and all eloralintide Phase 3 data are not yet public. The comparison table above will be updated as those appear.

These compounds are investigational. This article reports published and company-released clinical trial data for educational purposes and does not describe or endorse any use of any compound. It is not medical advice.