Why Every Drugmaker Now Wants an Amylin Drug

Five years ago, amylin drugs were a footnote: one mealtime diabetes injection that few people used. Now Novo Nordisk, Eli Lilly, Roche, AbbVie and Pfizer all have amylin-based obesity drugs in development, and three of those companies have reached phase 3 trials or beyond. The interest is real, and so are some of the results. But almost everything in this class is still investigational, most of the data come from the companies developing the drugs, and the idea that amylin produces "better" weight loss than GLP-1 drugs is still a hypothesis rather than a finding.

This explainer covers what amylin does, why the first amylin drug never became a weight-loss treatment, what each of the newer candidates has shown so far, and what nobody yet knows. It gives no dosing information and is not medical advice. None of the drugs below except pramlintide is approved anywhere, and products sold online under these names are not the medicines being tested; our report on what lab tests and FDA warnings show about online peptides explains why.

What amylin is

Amylin is a 37-amino-acid hormone made by the same pancreatic beta cells that make insulin, and it is released alongside insulin after a meal.¹ It acts mainly on the brain, in areas outside the blood-brain barrier that sense hormones in the blood, and it does three things that matter for weight and blood sugar: it slows how fast the stomach empties, it holds back glucagon (the hormone that raises blood sugar), and it makes people feel full sooner.¹²

That is a different route to the same goal as GLP-1 drugs such as semaglutide and tirzepatide, which act on their own receptors. The two systems overlap in the brain, and animal work suggested they add to each other.¹ That is the core reason companies are pairing amylin drugs with GLP-1 drugs, or building single molecules that hit both.

Amylin's receptors are unusual. They are made by combining the calcitonin receptor with helper proteins, so drugs can be designed to act mostly on amylin receptors or on both amylin and calcitonin receptors. A 2026 review argues this choice may shape whether reduced eating comes from normal fullness or from nausea and malaise, but says the question is still open.²

The first amylin drug, and why it stayed small

Pramlintide (Symlin) was approved in the United States in 2005.³ Its label limits it to people with type 1 or type 2 diabetes who use mealtime insulin and have not reached their blood-sugar goals. It carries a boxed warning: used with insulin, it increases the risk of severe low blood sugar, particularly in type 1 diabetes.³

Pramlintide was also tested for obesity. In a 12-month study in people without diabetes, the better-performing regimens produced roughly 6% to 7% more weight loss than placebo, with nausea the most common side effect.⁴ That was a real effect, but it needed injections at mealtimes, several times a day, and it was never approved for weight loss. Our cagrilintide vs pramlintide comparison covers the two side by side.

What changed is chemistry. Newer amylin analogues last long enough in the body to be injected once a week, and at least one is being tested as a daily tablet.² That made amylin practical to combine with weekly GLP-1 drugs.

Where each candidate stands

The table lists the amylin-based drugs with published human results or registered phase 3 trials, as of 3 November 2026. Weight-loss figures come from different trials with different lengths, populations and analysis methods, so they cannot be compared directly across rows.

CagriSema: the furthest along, and a reality check

Cagrilintide on its own produced 6% to 11% weight loss across doses in a 26-week phase 2 trial, against 3% with placebo, and slightly more than liraglutide at its highest dose.⁵ Combined with semaglutide as CagriSema, it produced an average weight loss of 20.4% at 68 weeks in the REDEFINE 1 trial, against 3.0% with placebo. That figure counts everyone randomised, including people who stopped treatment. Gastrointestinal side effects affected 79.6% of people on CagriSema and 39.9% on placebo, mostly mild to moderate and temporary.⁶

The reality check came in February 2026. In REDEFINE 4, an open-label head-to-head trial, CagriSema did not meet its goal of showing that it was no worse than tirzepatide: weight loss at 84 weeks was 23.0% against 25.5% if everyone stayed on treatment, and 20.2% against 23.6% counting everyone randomised.⁷ Novo said at the time that it expected an FDA decision on CagriSema for weight management by late 2026; when we checked on 3 November 2026, none had been announced.⁷ Our explainer on CagriSema's FDA review covers the filing and how it compares with Wegovy and Zepbound, and our cagrilintide profile covers the earlier trials.

Zenagamtide: one molecule, two targets

Novo's second approach puts GLP-1 and amylin activity into a single molecule. It was called amycretin until 2026; a Lancet paper published that year uses the new name zenagamtide and describes it as acting on GLP-1, amylin and calcitonin receptors.⁹

In a phase 1b/2a trial of the weekly injection, the highest dose produced 24.3% average weight loss at 36 weeks against 1.1% with placebo.⁸ Those numbers are striking but fragile: 125 people were spread across several dose groups, and the authors note that a large number withdrew. Side effects were mostly gastrointestinal.⁸ A daily tablet version lowered HbA1c by up to 1.4 percentage points over 36 weeks in a phase 2 trial in type 2 diabetes.⁹

Phase 3 is now under way. The registry lists AMAZE 7, comparing the injection with semaglutide for weight loss, and AMAZE 9, testing the tablet; both began recruiting in 2026. A cardiovascular outcomes trial, AMBIENCE, plans to enrol 8,500 people with established heart disease and is not yet recruiting.¹⁰

Eloralintide and EloraTZP: Lilly's entry

Lilly's eloralintide is a selective amylin receptor agonist. In a 48-week phase 2 trial in 263 adults without diabetes, average weight loss reached about 20% at the higher doses, against 0.4% with placebo, assuming everyone stayed on treatment.¹¹ The side effects deserve attention: at some doses, more than half of participants reported nausea, and fatigue was reported by up to 46%, against 14% and 12% with placebo.¹¹ Lilly's phase 3 programme, ENLIGHTEN, began enrolling in December 2025.¹²

Lilly is also pairing eloralintide with tirzepatide. In a 48-week phase 2b trial in 367 adults with type 2 diabetes, presented at a European diabetes meeting in September 2026, the highest combination dose produced 23.3% weight loss against 14.8% with tirzepatide alone, according to conference coverage. The same report put discontinuation because of side effects at 10.8% to 27.0% in the combination groups, against 2.9% with tirzepatide alone.¹³ Those results have not yet been published in a journal. Lilly has registered phase 3 trials of a combined product, called AMPLIFY, which had not started recruiting when we checked.¹³

Petrelintide: the tolerability bet

Petrelintide, from Zealand Pharma, is the candidate most often pitched on tolerability rather than size of effect. In the ZUPREME 1 phase 2 trial, published in November 2026, weight loss at 28 weeks was 7.9% to 9.8% across doses against 1.7% with placebo, reaching up to 10.7% by week 42.¹⁴ About a fifth of people on petrelintide reported nausea, mostly mild and during dose escalation, against 6% on placebo; vomiting, diarrhoea and constipation were about as common as on placebo.¹⁴

That is a smaller weight loss than the GLP-1 combinations, and it was a shorter trial. The case being made is that a gentler drug could be used alone by people who cannot tolerate GLP-1 drugs, or combined with one. Roche is running phase 3 trials, ZUPREME-3 and ZUPREME-5, which began in September 2026; ZUPREME-5 is in people with established heart disease but measures weight change, not heart attacks or strokes.¹⁵

Why the rush

Some of the reasons are scientific and some are commercial, and it helps to keep them apart.

The scientific case is that amylin works through a different pathway from GLP-1 and appears to add to it, so combinations may reach greater weight loss than either alone.¹² That has partial support: CagriSema beat both of its components in REDEFINE 1, and EloraTZP beat tirzepatide alone in its phase 2b trial.⁶¹³

The tolerability case is less settled. Roche said when it licensed petrelintide that the drug could "deliver weight loss comparable to GLP-1 receptor agonists but with improved tolerability", and described the aim as "high-quality weight loss".¹⁶ Those are company expectations. Petrelintide's phase 2 nausea rates were modest, but eloralintide's were high at some doses, and no amylin drug has yet been compared head-to-head with a GLP-1 drug for side effects in a large trial.¹¹¹⁴ Claims that amylin drugs preserve more muscle are, so far, not backed by published human trial results.

The commercial case is visible in the deals. Roche agreed to pay Zealand $1.65 billion upfront, in a deal worth up to $5.3 billion, for petrelintide in March 2025.¹⁶ AbbVie paid Gubra $350 million upfront the same month for a phase 1 amylin analogue.¹⁷ Pfizer's $7 billion acquisition of Metsera, completed in November 2025, included a monthly amylin candidate.¹⁸ For companies without a leading GLP-1 drug, amylin is one of the few routes into a market that Novo and Lilly dominate.

What is still unknown

• Long-term safety. The largest completed amylin-combination trials ran 68 to 84 weeks. Nothing is known yet about use over many years.
• Heart and kidney outcomes. No amylin-based obesity drug has outcome results. AMBIENCE, for zenagamtide, is the first such trial listed, and it is not yet recruiting.¹⁰
• Head-to-head comparisons. Apart from REDEFINE 4, no amylin drug has been tested directly against the best current treatment.⁷
• What happens after stopping. Weight regain after stopping GLP-1 drugs is well documented; our article on stopping semaglutide or tirzepatide covers it. There are no comparable data for the new amylin drugs.
• Independent analysis. Every trial above was funded by the company developing the drug, and several key results are still press releases or conference presentations.⁷¹³

What this means for you now

For now, the only amylin drug you can be prescribed is pramlintide, and only for diabetes treated with mealtime insulin.³ CagriSema could become the first amylin-based obesity treatment if the FDA approves it; the others are at least two years from any approval decision, based on their registered trial timelines.¹⁰¹²¹⁵ If you want access to one of these drugs before then, the legal route is a clinical trial; our guide to joining a weight-loss drug trial explains how. Our overview of where the next weight-loss drugs stand covers the wider pipeline.