Lilly and Novo Nordisk are pursuing amylin-based drugs because amylin is a distinct hormone pathway that could complement GLP-1 signaling. Their strategies range from amylin-only medicines to combinations with GLP-1 drugs and a single molecule designed to activate both pathways. The rationale is promising, but the trials reported so far do not establish that an amylin approach is better than a GLP-1 drug—or that one company’s program is ahead on effectiveness.
What amylin adds to the obesity-drug playbook
GLP-1 medicines target the GLP-1 receptor. Amylin is a separate hormone pathway, and the companies are testing whether targeting it can add to the effects of incretin medicines such as semaglutide and tirzepatide. That is the development rationale, not proof that combining pathways will produce greater or more durable weight loss.
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The phrase “after GLP-1s” can make these programs sound like replacements. Most of the strategies described here instead add amylin activity alongside GLP-1 activity, either by combining drugs or by designing a molecule with activity at both receptors. The companies are also testing amylin medicines on their own.
How Novo and Lilly are designing their programs
The approaches differ in whether amylin activity comes from a separate drug, a drug combination, or a single molecule. The development stages below reflect company materials available through October 3, 2026; they are not marketing approvals.
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| Program | Design | Reported development status |
|---|---|---|
| Novo: cagrilintide | A long-acting amylin analogue, studied alone and with semaglutide. | Novo’s 2025 annual report said its dedicated obesity program, RENEW, had initiated RENEW 1 and RENEW 2. |
| Novo: CagriSema | Cagrilintide plus semaglutide, combining amylin and GLP-1 activity through two medicines. | Novo reported submitting a US FDA new drug application for weight management. A submission is not an approval. The REDEFINE program studies people with overweight or obesity, with and without type 2 diabetes. |
| Novo: zenagamtide, formerly amycretin | One long-acting molecule with GLP-1 and amylin receptor agonist activity. | Novo’s 2025 annual report said Phase 3 weight-management development was underway in the first quarter of 2026, with subcutaneous and oral forms in development. |
| Lilly: eloralintide | A once-weekly selective amylin receptor agonist, formerly known as LY3841136. | Lilly reports Phase 3 development as a monotherapy for obesity and has also studied it alongside incretin therapy. |
| Lilly: EloraTZP | Eloralintide plus tirzepatide, engaging amylin, GIP and GLP-1 pathways. | Lilly’s September 30, 2026 announcement described a Phase 2b study using separate injections and said it planned to advance a co-formulation into Phase 3 by the end of 2026. |
What the reported trial results show—and what they cannot show
The figures below come from different trials, with different populations, durations, comparators and analysis methods. They are company-reported results, not a head-to-head comparison between drugs or companies.
| Drug or regimen | Reported result | Important context |
|---|---|---|
| Eloralintide alone | At 48 weeks, mean weight reduction ranged from 9.5% to 20.1% with eloralintide, versus 0.4% with placebo. | Eli Lilly and Company reported the Phase 2 results in 2025. The 263 participants had overweight or obesity, at least one weight-related comorbidity and no type 2 diabetes. The figures use the efficacy estimand; Lilly said all treatment arms met the primary endpoint. |
| EloraTZP | At 48 weeks, Lilly reported up to 23.3% mean weight loss with EloraTZP versus 14.8% with tirzepatide 15 mg. Maximum average A1C reductions were 2.9% and 2.4%, respectively. | Eli Lilly and Company reported the Phase 2b results in 2026 in 367 adults with overweight or obesity and type 2 diabetes. Both groups were in that trial population. Lilly said Phase 3 combination trials would start in the fourth quarter of 2026. |
| Cagrilintide alone | At 68 weeks, average body-weight reduction was 11.8% with cagrilintide 2.4 mg versus 2.3% with placebo. | Novo Nordisk reported this REDEFINE 1 sub-analysis in its 2025 annual report. It covered participants who adhered to treatment, not all randomized participants. |
| CagriSema | Novo characterizes results as additive, but the cited company materials do not provide a comparable numeric result here. | Novo described REDEFINE 4 as an open-label Phase 3 comparison. Its interpretation of results should be treated as the company’s characterization, not as proof that CagriSema is superior to other programs. |
| Zenagamtide | No numerical efficacy figure is included here. | Novo has reported Phase 2 data and advanced subcutaneous and oral forms toward Phase 3, but the cited materials do not provide enough detail for a numerical comparison with the other candidates. |
Even results from the same trial require attention to dose, comparator, analysis method and who remained on treatment. A percentage from one study cannot establish how the drug would compare in another trial or perform in routine care.
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What would make an amylin strategy matter to patients
The mechanism is only one part of the decision. To judge whether these candidates offer a meaningful option, readers will need results that make clear:
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- Who was studied: whether participants had type 2 diabetes or other weight-related conditions, and how closely they resemble the people a medicine is intended to treat.
- What was compared: whether the control was placebo or an active medicine, and whether the trial was designed to test superiority or another outcome.
- How outcomes were analyzed: trial duration, dose, estimand and whether the reported population includes all randomized participants or only people who adhered to treatment.
- How treatment was tolerated: side effects, discontinuations and whether people can stay on the regimen. The results summarized here do not establish a comparative tolerability advantage.
- How it is taken: whether a candidate is injectable or oral, how often it is dosed, and whether a combination uses separate injections or a co-formulation.
- Where it stands with regulators: a trial result, a planned Phase 3 start and an FDA application are different milestones; none should be mistaken for approval.
Why there is no clear winner yet
Novo is pursuing three distinct formats: an amylin analogue, a two-drug combination with semaglutide, and a single molecule with both GLP-1 and amylin receptor activity. Lilly is advancing a selective amylin agonist and a combination with tirzepatide. These designs test different ways of adding amylin activity; they do not yet show which design best balances weight outcomes, tolerability, convenience and sustained use.
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The reported trial populations and methods also differ. Lilly’s EloraTZP results came from a Phase 2b study in people with type 2 diabetes, while Novo’s cited cagrilintide percentage is an adherent-participant sub-analysis. Comparing those numbers as if they were results from a shared contest would be misleading. The available company announcements describe a field in development, not an established successor to GLP-1 medicines.
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