Do Amylin Drugs Work as Well as GLP-1s? What the Trials Measured

One amylin drug has been on the market since 2005. Its own label puts the weight change at 1.33 to 1.6 kg, and it is not a weight-loss drug at all.¹

Newer analogs report 9.2% to 22.0%.^{2 3 4 5}

That gap is real and it is not a scandal. Old drug and new ones were made for different jobs. They were given at different doses and tested in different people. Most coverage prints the new numbers with the old one nowhere in sight.

Is any amylin drug approved?

One. Pramlintide, sold as SYMLIN. The FDA label describes it as "indicated as an adjunctive treatment in patients with type 1 or type 2 diabetes" who use mealtime insulin and have not reached their glucose targets.¹ Nothing in that indication mentions weight.

Weight appears in the label as a trial observation. In the type 1 dose-titration study the label records a "mean reduction of -1.33 kg in the SYMLIN treatment group" against a mean gain on placebo. In the type 2 trials it records "mean reductions of -1.4 kg, and -1.6 kg."¹ Those are the numbers the FDA reviewed, in the population the drug was approved for. The class has therefore had a product on pharmacy shelves for two decades, and in people taking mealtime insulin it moves weight by about a kilogram and a half.

How much weight did each new one cause?

Weight loss ran between 9.2% and 22.0%, depending on the compound, the dose and which trial you read.^{2 3 4 5}

Compound	Trial	People	Weeks	Top result	Placebo	Status
Petrelintide	ZUPREME-12	493	42	10.7%	1.7% loss	Topline, final data not yet presented
Petrelintide	ZUPREME-23	220	28	9.2%	2.0% loss	Topline
Eloralintide	Phase 24	263	48	20.1%	0.4% loss	Published in The Lancet
Amycretin	Phase 1b/2a5	125	36	22.0%	1.9% to 2.3% gain	Topline
Amycretin, oral	Phase 16	not stated	12	13.1%	1.1% loss	Presented at EASD 2024

Every number in that table is the efficacy estimand, taken from the highest-dose arm instead of the average across arms.

The eloralintide trial published its full dose ladder. That ladder is the useful part. Lilly reports 1 mg at "-9.5% (-10.2 kg; -22.5 lbs)", 3 mg at "-12.4% (-13.3 kg; -29.3 lbs)", 6 mg at "-17.6% (-18.7 kg; -41.2 lbs)" and 9 mg at "-20.1% (-21.3 kg; -47.0 lbs)", against placebo at "-0.4% (-0.2 kg; -0.4 lbs)".⁴ Two escalation schedules sat alongside the fixed doses, a 6/9 mg arm reaching -19.9% and a 3/6/9 mg arm reaching -16.4%.The headline everywhere is 20.1%.

Its 1 mg arm produced under half of that. Petrelintide's ZUPREME-2 release gives a range too, reporting 7.4% to 9.2% across its three arms, so its lowest arm reached about four fifths of the quoted figure.³ These are trial doses, reported as citations and attached to no recommendation.

Amycretin is a dual agonist at the GLP-1 and amylin receptors, so it is not a clean read on amylin alone.⁵ Cagrilintide, the amylin half of CagriSema, has its own trial record covered on the CagriSema pages.

What does "efficacy estimand" mean?

The efficacy estimand answers what would have happened if everyone had stayed on the drug for the whole trial. Lilly's release spells that out, defining it as efficacy "had all randomized participants remained on study intervention" for 48 weeks.⁴ Three standard ways exist to summarize one trial, each producing a different number.

Novo states the same condition for amycretin in plain words. Those figures hold only if all participants "adhered to the planned dosing schedule for the full trial period without discontinuing treatment."⁵

Treatment-policy numbers count everyone as randomized, including the people who stopped taking the drug and the people who added another one. Trial-product numbers sit between the two. Three readings answer three different questions, so a single trial can honestly produce three different percentages. Picking one of the three is a framing decision.

None of these four releases gives a treatment-policy figure. The CagriSema filing page sets out how far apart the readings ran on a trial that published all of them, the nearest thing to a scale for what is missing here.

Petrelintide's ZUPREME-2 release reports "up to 9.2%" without naming which estimand produced it.³ The ZUPREME-1 release does name it.²

What does amylin actually do?

Amylin is a hormone the pancreas releases alongside insulin after a meal. The amylin analog group page lists every compound in the class, including the earlier-stage ones this page does not cover. It slows the rate at which the stomach empties and it adds to the feeling of fullness.

Those are the same two effects that make GLP-1 drugs work on appetite, reached through a different receptor. The two hormones are not interchangeable, so a drug can be built to hit one, the other, or both.

Amycretin is the both case, a single molecule agonizing the GLP-1 and the amylin receptor together.⁵ Native amylin also clumps in solution, so no drug is simply amylin. Pramlintide is an engineered analog stable enough to inject, and the newer compounds carry further modifications that stretch the half-life from hours to a week.^{1 2 4}

Why is the approved drug so much weaker?

The approved drug is weaker for three design reasons, none of them biological.

Pramlintide is short-acting and taken at meals alongside insulin, while the new analogs are engineered for once-weekly dosing.¹ A weekly drug holds a concentration across the whole week instead of producing a spike at each meal, so total exposure is continuous and far larger. Doses are larger too. Eloralintide's trial arms ran to 9 mg weekly and amycretin's to 20 mg weekly, figures reported here as trial doses and attached to no recommendation.^{4 5}

Populations differ most of all. Pramlintide's label trials enrolled patients with diabetes already on mealtime insulin, where weight gain is a known effect of the insulin itself.¹ ZUPREME-1 and the eloralintide trial enrolled people with overweight or obesity, and ZUPREME-2 required both obesity and type 2 diabetes for entry.^{2 3 4}

Why are these being tested as add-ons to GLP-1s?

They are tested as add-ons because that is where the commercial bet sits. Their trial programs show it plainly. Cagrilintide reached phase 3 as half of CagriSema, co-formulated with semaglutide instead of running alone.⁷ The eloralintide guide covers its other phase 2, the one that paired it with tirzepatide. Amycretin skips the pairing by building both activities into one molecule.⁵

A reader looking for an amylin drug to take by itself therefore finds a thinner record than the headline numbers suggest. Petrelintide and eloralintide monotherapy are the two real standalone datasets, at 493 and 220 people and 263 people respectively.^{2 3 4} Both are phase 2. Neither has a phase 3 result, and a phase 2 result in 263 people is where semaglutide and tirzepatide also looked excellent before their larger trials refined the numbers downward.

Has any amylin drug been tested against a GLP-1?

Only once, five years ago. The cagrilintide phase 2 trial describes itself in its own title as "a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial," published in The Lancet in 2021.⁷

Everything since has used placebo. ZUPREME-1 compared five doses of petrelintide against placebo, ZUPREME-2 compared three. The eloralintide trial compared six arms against placebo.^{2 3 4} The cagrilintide paper is not reachable from here, so this page names its design from its own published title and quotes no figure out of it.⁷ What the title does establish is that an active comparator existed in 2021 and has not appeared in a reported amylin monotherapy trial since.

So the question in the title has barely been asked. A 20.1% result against a 0.4% placebo is a different claim from a 20% result against an active comparator. Only the first kind has been made in this class since 2021.

Which results are published, and which are press releases?

Only the eloralintide results are published in a journal. Lilly's release states that results "were presented at ObesityWeek 2025 and simultaneously published in The Lancet."⁴

Both petrelintide readouts are company topline announcements. Roche's ZUPREME-1 release says the final data "will be presented at an upcoming medical congress," which means the full result was not public when the percentage was.² Amycretin's figures came from a Novo topline announcement.⁵

A topline release is the company's own summary of its own trial, written before anyone outside has seen the dataset. Topline releases therefore establish what the company claimed. Whatever dataset sits behind them stays unseen until the congress presentation.

Is there an oral amylin drug?

One oral candidate has human data, and it is amycretin again. The same molecule has a separate daily tablet program, reported in a "single-centre, placebo-controlled, double-blinded phase 1 study" presented at the European Association for the Study of Diabetes meeting in September 2024.⁶

Participants on 50 mg "reduced their body weight by 10.4%, on average, within 12 weeks of treatment", and the maximum dose tested, 2x50 mg, "achieved a body weight reduction of 13.1%".⁶ Placebo over the same period averaged 1.1%.The release does not state how many people were in the trial.

The oral program is daily and the injectable one is weekly, so the two amycretin figures come from different schedules as well as different routes and durations, and 13.1% at 12 weeks cannot be set against 22.0% at 36 weeks as though one were a weaker version of the other.^{5 6} Side-effects were described as "mainly mild to moderate in severity and of gastrointestinal nature including nausea and vomiting", with no percentages given.

The release also records that all co-authors are Novo Nordisk employees and shareholders.⁶ That is normal for a phase 1 readout. Novo is still the party reporting on its own molecule.

Does amycretin's dose-response mean what it looks like?

No. The release says why in its own parentheses. Novo gives "9.7% on 1.25mg (20 weeks), 16.2% on 5mg (28 weeks) and 22.0% on 20mg (36 weeks)."⁵

Each dose was measured at a different timepoint. The highest dose also ran the longest, so dose and duration move together and the trial cannot separate them. Some share of that 22.0% is duration, and the release gives no way to say how much.

The placebo arms moved the other way, gaining an estimated 1.9%, 2.3% and 2.0%.⁵

Are amylin drugs better tolerated than GLP-1s?

Not against a GLP-1. No trial has made that comparison, and the petrelintide numbers that point that way are the least reported part of the data.

In ZUPREME-1 the discontinuation rate from adverse events was "4.8% with petrelintide" in the maximally effective arm against "4.9% with placebo," with "no vomiting in the maximally effective treatment arm."² Withdrawal for any reason ran 8.4% across petrelintide arms against 13.6% on placebo.

ZUPREME-2 reports gastrointestinal discontinuation at 1.9% against 1.7% on placebo.³

Placebo matching placebo-level dropout is a real signal and it is not the same as a head-to-head against semaglutide. Lilly's eloralintide release reports no discontinuation figure at all, saying only that the commonest events were "mild to moderate gastrointestinal symptoms and fatigue."⁴

What did ZUPREME-2 show on blood sugar?

ZUPREME-2 showed a reduction in HbA1c "of up to 0.65% versus an increase of 0.23% with placebo."³ HbA1c is the share of hemoglobin carrying attached glucose, and it tracks average blood sugar over roughly three months.

Placebo direction is the part to notice. Blood sugar did not merely improve less on placebo. It moved the wrong way. A 0.65% reduction against a 0.23% rise is therefore a gap of nearly nine tenths of a point between the arms.

This is also the only glycemic result in the set. ZUPREME-1 did not require diabetes for entry and reports no comparable figure, the eloralintide phase 2 enrolled people with obesity or overweight, and the amycretin readouts are weight-first.^{2 4 5} Pramlintide, the one approved drug in the class, is indicated for glucose control and not for weight, so the class has spent twenty years pointed at the endpoint its newest trials mostly do not measure.¹

That trial enrolled 220 people in the United States who had both overweight or obesity and type 2 diabetes.³ The weight result across its three arms ran 7.4% to 9.2%, so the lowest arm produced about four fifths of what the headline quotes.

Why do the two petrelintide numbers differ?

The two petrelintide numbers differ because they come from two trials with different entry criteria, measured at different weeks. Coverage has reported 10.7% and 9.2% as though one superseded the other.

ZUPREME-1 ran in 493 people with overweight or obesity and reported 10.7% at week 42.² ZUPREME-2 ran in 220 people who also had type 2 diabetes and reported 9.2% at week 28.³ ZUPREME-2 required type 2 diabetes for entry and ZUPREME-1 did not, and week 42 sits fourteen weeks further into treatment than week 28.

Neither figure is wrong. Reading them as a change over time is the error.

What would settle this?

One trial would settle it: an amylin analog against semaglutide or tirzepatide at doses people actually take, reporting the treatment-policy estimand alongside the efficacy one, and published in a journal instead of announced in a release.

Four smaller gaps sit underneath that. No phase 3 monotherapy result exists for any selective amylin analog, so every percentage on this page comes from phase 1 or phase 2. None of the releases reports lean mass or any body-composition split, so the question covered on the muscle and GLP-1 guide has no amylin answer at all. Nothing reports what happens after stopping. And the participant counts are small, at 493, 263, 220 and 125, with the oral amycretin trial not disclosing its number.^{2 3 4 5 6}

Until then the class holds one approved drug that moves weight by a kilogram and a half. Four investigational readouts report 9.2% to 22.0%, all under the most favorable of three readings. One comparison against another drug exists. That one dates from 2021.

Common questions

Are amylin analogs the same as GLP-1 drugs?

Is any amylin analog approved for weight loss?

Which amylin drug has the strongest result?

Is eloralintide stronger than semaglutide?

How many people were in these trials?

Why does the placebo group gain weight in the amycretin trial?

Who is developing each one?

What is pramlintide used for now?

Can you compare these trials directly?

Is there an oral amylin pill?

What dose did these trials use?

Does the weight loss plateau?

What is cagrilintide, and where does it fit?

Can you buy any of these?

What should I watch for next?

Sources

1. FDA-approved prescribing information for SYMLIN (pramlintide acetate), retrieved from the openFDA drug label API. Read at source. https://api.fda.gov/drug/label.json?search=openfda.generic_name:%22pramlintide%22 ↩1 ↩2 ↩3 ↩4 ↩5 ↩6 ↩7
2. Roche, "Roche announces positive Phase II results for petrelintide, an amylin analog developed for people living with overweight and obesity," company media release, March 5, 2026. Trial NCT06662539. Company topline announcement, not a peer-reviewed publication. Read at source. https://www.roche.com/media/releases/med-cor-2026-03-05 ↩1 ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13
3. Zealand Pharma, "Zealand Pharma announces positive Phase 2 ZUPREME-2 topline results for amylin analog petrelintide in people with overweight or obesity and type 2 diabetes," company announcement, October 7, 2026. Company topline announcement, not a peer-reviewed publication. Read at source. https://www.globenewswire.com/news-release/2026/10/07/3376750/0/en/zealand-pharma-announces-positive-phase-2-zupreme-2-topline-results-for-amylin-analog-petrelintide-in-people-with-overweight-or-obesity-and-type-2-diabetes.html ↩1 ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13
4. Eli Lilly and Company, "Lilly's selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight," company press release. Trial NCT06230523. States the results were presented at ObesityWeek 2025 and published simultaneously in The Lancet. Company release read at source; the journal article itself was not read. https://www.prnewswire.com/news-releases/lillys-selective-amylin-agonist-eloralintide-demonstrated-meaningful-weight-loss-and-favorable-tolerability-in-a-phase-2-study-of-adults-with-obesity-or-overweight-302607061.html ↩1 ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13 ↩14
5. Novo Nordisk, company announcement of topline results for amycretin in a phase 1b/2a trial with once-weekly subcutaneous administration. Company topline announcement, not a peer-reviewed publication. Read at source. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=915251 ↩1 ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13 ↩14
6. "Weight loss of up to 13% achieved in three months with once-a-day tablet, phase 1 trial finds," news release for a phase 1 oral amycretin study presented at the European Association for the Study of Diabetes annual meeting, Madrid, September 9 to 13, 2024. The release records that all co-authors are Novo Nordisk employees and shareholders. Conference presentation reported via a press release, not a peer-reviewed publication. Read at source. https://www.eurekalert.org/news-releases/1057197 ↩1 ↩2 ↩3 ↩4 ↩5 ↩6
7. Lau DCW and colleagues, "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial," The Lancet, 2021, DOI 10.1016/s0140-6736(21)01751-7. Title, journal, year and DOI verified at source via the Crossref API; the full text is not reachable from here and no figure from it is quoted on this page. ↩1 ↩2 ↩3