For nearly a decade the obesity conversation has been dominated by one hormone class: GLP-1. Semaglutide, tirzepatide, and retatrutide all work by mimicking or amplifying gut incretin signals. But a second satiety hormone, amylin, is now driving the most talked-about next wave of weight management drugs. Two molecules sit at the front of that wave: petrelintide, Zealand Pharma's once-weekly amylin analog now partnered with Roche, and eloralintide, Eli Lilly's selective amylin receptor agonist that posted up to 20% weight loss in a Phase 2 trial. Both are positioned as cleaner, better-tolerated successors to CagriSema. This guide explains what amylin analogs are, how petrelintide and eloralintide differ, what their human data actually shows, and where they fit in the 2026 to 2027 obesity pipeline.
🔑 Key Takeaways
- Petrelintide and eloralintide are amylin receptor agonists, a different satiety pathway from GLP-1 drugs, and both are once-weekly subcutaneous injections still in clinical trials with no FDA approval.
- Eloralintide (Eli Lilly, formerly LY3841136) hit up to 20.1% mean weight loss at 48 weeks in its Phase 2 study, published in The Lancet.[5][6]
- Petrelintide (Zealand Pharma, partnered with Roche) produced 10.7% weight loss at week 42 in the ZUPREME-1 trial with placebo-like tolerability and zero vomiting at the top dose.[1][2]
- The headline appeal is tolerability and lean-mass preservation: amylin analogs aim to deliver GLP-1-like weight loss with far less nausea and vomiting.[2][10]
- Both are being developed mainly as combination partners (petrelintide + CT-388, eloralintide + tirzepatide), not just standalone drugs. Neither is available to buy or prescribe in 2026.
What Are Amylin Analogs, and Why Does Amylin Matter for Weight?
Amylin is a 37-amino-acid peptide hormone co-secreted with insulin from the pancreatic beta cells after you eat. It binds receptors in the hindbrain area postrema, which then activate downstream brain regions that control appetite, gastric emptying, and the sense of fullness.[9] In plain terms, amylin is one of the body's natural "stop eating" signals, and it works through a satiety circuit that is largely separate from the GLP-1 pathway most weight-loss drugs target.
What makes amylin especially interesting is its effect on leptin. Research indexed by the NIH describes amylin as a "leptin sensitizer": it restores the brain's responsiveness to leptin, the hormone that signals long-term energy stores, in part by stimulating IL-6 production from hypothalamic microglia.[9][10] Because obesity is characterized by leptin resistance, an agent that re-opens that signaling pathway is mechanistically attractive in a way that GLP-1 drugs are not.
The first amylin analog in clinical use was pramlintide (Symlin), approved as a mealtime injection alongside insulin. Pramlintide proved the concept that amylin agonism reduces food intake and body weight, but its short half-life required dosing with every meal, which killed its practicality for obesity. The new generation, petrelintide and eloralintide, solves that problem with engineered once-weekly molecules. They sit alongside cagrilintide, the amylin analog in Novo Nordisk's CagriSema combination, as the three leading long-acting amylin candidates.
Amylin vs GLP-1 in one sentence
GLP-1 drugs slow the gut and dampen appetite through the incretin system, which is powerful but drives nausea and vomiting; amylin analogs target a parallel hindbrain satiety circuit and a leptin-sensitizing mechanism, aiming for similar weight loss with a calmer stomach.[9][10]
Petrelintide: Zealand Pharma's Roche-Backed Amylin Analog
Petrelintide (development code ZP8396) is a long-acting amylin analog engineered for once-weekly subcutaneous dosing. A key design feature is its chemical and physical stability with no fibrillation around neutral pH, which is what allows it to be co-formulated and co-administered with other peptides, making it an ideal backbone for combination products.[3]
The ZUPREME-1 Phase 2 data
On March 5, 2026, Zealand Pharma reported topline Phase 2 results from ZUPREME-1, a randomized, double-blind, placebo-controlled dose-finding trial in 493 people with overweight or obesity (53% female, mean baseline BMI 37 kg/m2). The trial ran across 33 sites in the United States, Poland, and Romania, with a 16-week dose-escalation period (stepping up every fourth week) followed by maintenance to week 42.[1][2]
At the maximally effective dose, petrelintide produced a 10.7% mean body weight reduction at week 42 versus 1.7% for placebo (p less than 0.001).[1] What drew the most attention, though, was the tolerability profile:
- Zero cases of vomiting in the maximally effective dose arm.[1]
- Almost no nausea reported once participants reached their target maintenance dose.[2]
- Treatment discontinuation due to adverse events of just 4.8% on petrelintide versus 4.9% on placebo, essentially identical.[1]
- Lower overall trial withdrawal on drug (8.4%) than on placebo (13.6%).[1]
That placebo-like tolerability is the entire investment thesis for amylin monotherapy: weight loss in the low double digits without the GI burden that pushes many patients off GLP-1 therapy.
The Roche deal and the road to Phase 3
In March 2025, Roche signed an exclusive collaboration and licensing agreement with Zealand Pharma to co-develop and co-commercialize petrelintide, paying $1.65 billion upfront with the deal potentially worth up to $5.3 billion in milestones and sales incentives.[3][4] The collaboration is built around two products: petrelintide as a monotherapy, and a fixed-dose combination of petrelintide with CT-388, Roche's dual GLP-1/GIP receptor agonist, aimed at patients who need more weight loss or glycemic control than amylin alone provides.[3] Phase 3 trials for chronic weight management are planned to begin in the second half of 2026.[3]
Eloralintide: Eli Lilly's Selective Amylin Agonist
Eloralintide (formerly LY3841136) is an investigational once-weekly, selective amylin receptor agonist from Eli Lilly. The "selective" label matters: it is engineered to target the amylin receptor specifically rather than also hitting the closely related calcitonin receptor, which Lilly argues should sharpen its satiety effect.[5]
The Phase 2 trial that turned heads
Eloralintide's Phase 2 study (NCT06230523) was a 48-week, randomized, double-blind, placebo-controlled trial of once-weekly monotherapy in 263 adults with obesity or overweight and at least one weight-related comorbidity, without type 2 diabetes, run across 46 US research centers.[5][8] The results were presented at ObesityWeek 2025 and published simultaneously in The Lancet.[6][7]
All treatment arms met the primary endpoint, with mean weight reductions of 9.5% to 20.1% versus just 0.4% on placebo. The top fixed-dose arm reached 20.1% mean body weight loss at 48 weeks, putting eloralintide monotherapy in the same range as the best dual and triple agonists.[5] The most common adverse events were mild-to-moderate gastrointestinal symptoms (nausea) and fatigue, with lower incidence when the dose was escalated more slowly.[5][7]
What's next for eloralintide
Lilly planned to begin Phase 3 monotherapy enrollment by year-end 2025 and is also running a Phase 2 combination study (NCT06603571) testing eloralintide alone or with tirzepatide for weight management in adults with obesity and type 2 diabetes.[5] Like Roche and Zealand, Lilly clearly sees the future of amylin as both a standalone option and a combination building block.
Petrelintide vs Eloralintide: Side-by-Side Comparison
These two molecules are at different points in development and were tested in different trials, so a head-to-head efficacy ranking is not yet valid. Still, putting the published numbers next to each other clarifies how they differ.
| Attribute | Petrelintide (ZP8396) | Eloralintide (LY3841136) |
|---|---|---|
| Developer | Zealand Pharma + Roche | Eli Lilly |
| Class | Long-acting amylin analog | Selective amylin receptor agonist |
| Route / frequency | Subcutaneous, once weekly | Subcutaneous, once weekly |
| Phase 2 trial | ZUPREME-1, n=493 | NCT06230523, n=263 |
| Trial duration | 42 weeks (followed to 51) | 48 weeks |
| Top-dose weight loss | 10.7% at week 42 | 20.1% at 48 weeks |
| Placebo weight loss | 1.7% | 0.4% |
| Standout tolerability note | 0 vomiting at max effective dose; discontinuations equal to placebo | Mostly mild-to-moderate nausea and fatigue; better with slow titration |
| Lead combination partner | CT-388 (GLP-1/GIP) | Tirzepatide (GLP-1/GIP) |
| Phase 3 status (mid-2026) | Planned H2 2026 | Enrollment started late 2025 |
| FDA approval | No | No |
Sources for table figures: Zealand/Roche releases[1][2][3] and Lilly/Lancet Phase 2 data.[5][6] A direct efficacy comparison requires a head-to-head trial, which has not been run.
How These Numbers Translate to Real-World Weight
Percentages are abstract, so here is what the trial top-dose figures look like for people at common starting weights. These are illustrative projections based on the reported mean percentages, not individual guarantees.
| Starting weight | Petrelintide ~10.7% | Eloralintide ~20.1% |
|---|---|---|
| 90 kg (198 lb) | ~9.6 kg (21 lb) lost | ~18.1 kg (40 lb) lost |
| 100 kg (220 lb) | ~10.7 kg (24 lb) lost | ~20.1 kg (44 lb) lost |
| 110 kg (243 lb) | ~11.8 kg (26 lb) lost | ~22.1 kg (49 lb) lost |
| 120 kg (265 lb) | ~12.8 kg (28 lb) lost | ~24.1 kg (53 lb) lost |
Note the apples-to-oranges caveat: petrelintide's 10.7% was at week 42 from a dose-finding study, while eloralintide's 20.1% was at 48 weeks from its top fixed-dose arm. Trial weight loss usually exceeds what a typical patient achieves outside the controlled setting of a study.
The Tolerability and Lean-Mass Argument
Why is anyone excited about a drug that loses to tirzepatide and retatrutide on raw weight loss? Two reasons.
1. Tolerability. GLP-1 nausea and vomiting drive a meaningful share of patients to stop treatment. Petrelintide's near-placebo GI profile, with zero vomiting at its top effective dose and discontinuations matching placebo, suggests amylin monotherapy could keep more people on therapy long enough to benefit.[1][2]
2. Muscle preservation. A recurring concern with rapid GLP-1 weight loss is loss of lean (muscle) mass. Of the weight lost on semaglutide, roughly 45% has been attributed to lean mass, versus about 25% with tirzepatide.[10] Amylin analogs and amylin-GLP-1 combinations are being studied specifically for their potential to attenuate lean-mass loss and better preserve muscle composition, an emerging advantage over GLP-1 monotherapy.[10] If amylin can protect muscle while trimming fat, that changes the quality, not just the quantity, of weight loss.
Why combinations dominate the strategy
Both companies are designing amylin as a partner, not a solo act. Petrelintide pairs with CT-388 and eloralintide with tirzepatide, because stacking a calm amylin satiety signal onto a high-efficacy incretin drug aims to capture the best of both: GLP-1-class weight loss with amylin's gentler tolerability and muscle protection.[3][5]
Where Amylin Fits Among the Other Next-Gen Obesity Drugs
Amylin is one of several mechanisms competing for the post-semaglutide market. For context on how the broader field stacks up, see our overviews of all the GLP-1 medications and the best weight-loss peptides ranked. The closest amylin relatives to petrelintide and eloralintide are:
- Cagrilintide (Novo Nordisk): the amylin analog inside CagriSema. Combining cagrilintide with semaglutide produced about 20.4% weight loss at 68 weeks in trial data, beating either drug alone.[10] Petrelintide and eloralintide are explicitly positioned as cleaner-tolerated successors to this approach.
- Amycretin (Novo Nordisk): a single molecule that activates both amylin and GLP-1 receptors, available in oral and injectable forms.
If you want the standalone breakdown of the amylin analog already furthest along in combination form, our dedicated cagrilintide guide covers its dosing and trial data. And for the FDA-approved injectable options available right now while these candidates finish trials, see our roundup of weight-loss injections compared.
2026 to 2027 Amylin Pipeline Timeline
| Date | Milestone |
|---|---|
| March 2025 | Roche licenses petrelintide from Zealand ($1.65B upfront, up to $5.3B total)[3][4] |
| Late 2025 | Eloralintide Phase 2 presented at ObesityWeek, published in The Lancet; Phase 3 enrollment begins[5][6] |
| March 2026 | Petrelintide ZUPREME-1 Phase 2 topline reported (10.7% at week 42)[1] |
| H1 2026 | Planned start of petrelintide + CT-388 Phase 2 combination trial[3] |
| H2 2026 | Planned start of petrelintide Phase 3 program for chronic weight management[3] |
| 2027 and beyond | Earliest realistic window for Phase 3 readouts; regulatory filings would follow |
Frequently Asked Questions
The Bottom Line
Petrelintide and eloralintide represent the most credible attempt yet to win on tolerability rather than raw efficacy. Eloralintide's 20% top-dose weight loss shows amylin monotherapy can reach incretin-class numbers, while petrelintide's near-placebo GI profile shows it can do so without the nausea that drives patients off treatment. With Roche and Lilly both pushing combination products (petrelintide with CT-388, eloralintide with tirzepatide) into Phase 3, amylin is no longer a footnote to the GLP-1 story. It may become a foundational layer of obesity treatment. For now, though, both remain investigational: not approved, not prescribable, and not for sale. Anyone interested should follow the Phase 3 readouts expected from 2027 onward rather than seeking these molecules through unregulated channels.
References
- Zealand Pharma. Positive Phase 2 results for petrelintide (ZUPREME-1 topline). GlobeNewswire, March 5, 2026.
- BioSpace. Zealand Pharma announces positive Phase 2 results for petrelintide. March 2026.
- Roche. Exclusive collaboration and licensing agreement with Zealand Pharma to co-develop petrelintide. Media release, March 12, 2025.
- Pharmaceutical Executive. Zealand Pharma, Roche reach potential $5.3 billion deal to develop petrelintide. 2025.
- Eli Lilly / PR Newswire. Eloralintide demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study. 2025.
- Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2 randomised, placebo-controlled trial. The Lancet, 2025.
- Healio. Novel amylin receptor agonist induces clinically meaningful weight loss (ObesityWeek 2025). November 6, 2025.
- ClinicalTrials.gov. NCT06230523: Phase 2 study of eloralintide in adults with obesity or overweight.
- Boyle CN, et al. Control of energy homeostasis by amylin. PMC (NIH), 2024.
- Amylin Revisited: A 5-Year Perspective on Its Emerging Role in the Treatment of Diabesity. PMC (NIH), 2025.
