Petrelintide, Eloralintide and the Amylin Pipeline After CagriSema
No standalone amylin drug is approved for weight loss as of October 2026, but three are now in Phase 3: Lilly's eloralintide, Roche and Zealand's petrelintide, and Novo Nordisk's cagrilintide on its own. Eloralintide posted the biggest Phase 2 number (20.1% at 48 weeks on its top dose), while petrelintide's pitch is tolerability, with Phase 2 weight loss closer to 10%.
Key takeaways
- Eloralintide (Lilly): up to 20.1% mean weight loss at 48 weeks in Phase 2; the ENLIGHTEN Phase 3 trials started in February 2026.
- Petrelintide (Zealand/Roche): up to 10.7% at 42 weeks in ZUPREME-1, with side-effect dropouts matching placebo; Phase 3 began dosing in 2026.
- Cagrilintide alone produced 11.8% at 68 weeks in REDEFINE 1 and moved into its own Phase 3 program, RENEW.
- Pfizer (via Metsera), AstraZeneca and AbbVie have earlier-stage amylin drugs, including a candidate aimed at monthly dosing.
- Comparing these numbers across trials is risky. Doses, trial lengths and populations all differ.
Why drug companies are betting on amylin
Amylin is a hormone your pancreas releases alongside insulin after you eat. It slows stomach emptying, curbs glucagon release, and acts on appetite centers in the brain to make you feel full (Appleyard Lees review). It works through different receptors than GLP-1, which is why companies see it both as a stand-alone option and as a partner for GLP-1 drugs.
The idea is not new. Pramlintide (Symlin) has been FDA approved since 2005, but it has a half-life of about 48 minutes, must be injected right before each major meal, and carries a boxed warning for severe low blood sugar when used with insulin (Symlin prescribing information). The new generation is engineered to last a week or longer, and so far is being tested in people with obesity rather than only in insulin users.
The appeal, as PharmaVoice summarized it in late 2025, is weight loss "without the same degree of tolerability issues" seen with GLP-1s. That claim is still based on ongoing trials, so treat it as a hypothesis the Phase 3 programs need to confirm.
Eloralintide (Eli Lilly): the biggest Phase 2 number
Lilly's Phase 2 trial (NCT06230523) enrolled 263 adults with obesity, or overweight plus a related condition, and no type 2 diabetes. Average starting weight was 109.1 kg. Results were published in The Lancet in November 2025 (Lilly press release).
| Eloralintide arm (48 weeks) | Mean weight change |
|---|---|
| 1 mg | −9.5% |
| 3 mg | −12.4% |
| 6 mg | −17.6% |
| 9 mg | −20.1% |
| 6 mg then 9 mg | −19.9% |
| 3 mg, 6 mg, then 9 mg | −16.4% |
| Placebo | −0.4% |
Source: Eli Lilly, November 6, 2025 (efficacy estimand). Lilly's release did not report treatment-regimen estimand results.
Side effects were mostly mild-to-moderate GI symptoms and fatigue, more common at higher doses and less common with slower escalation. At 1 mg and 3 mg they were similar to placebo, per Lilly. The release did not give specific nausea, vomiting or dropout rates. BioSpace reported that key opinion leader feedback relayed in a Leerink note said mood effects "warrant close monitoring," something to watch in the larger trials.
The ENLIGHTEN Phase 3 program
- ENLIGHTEN-1: 1,980 adults with obesity or overweight and no type 2 diabetes, started February 6, 2026, main phase about 75 weeks, estimated primary completion March 2028 (registry record).
- ENLIGHTEN-6: 900 people with "persistent obesity" who are already on a weekly incretin drug, testing eloralintide added on top; started February 10, 2026, estimated primary completion June 2028 (registry record).
- Other registered trials cover type 2 diabetes (ENLIGHTEN-2) and sleep apnea (ENLIGHTEN-3).
ENLIGHTEN-6 is the one most relevant to current GLP-1 users. It asks whether adding an amylin drug helps people who plateaued on a weekly incretin. Lilly also tested eloralintide with tirzepatide in an earlier study, which produced 11.3% weight loss at 12 weeks (BioSpace).
Amylin drugs are years away
If you want treatment now, compare the GLP-1 options already on the market.
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Petrelintide (Zealand Pharma and Roche): the tolerability play
Roche licensed petrelintide from Zealand for $1.65 billion, with shared development and commercialization rights (PharmaVoice). It now has two Phase 2 readouts.
ZUPREME-1 (obesity, no diabetes)
The trial randomized 493 adults (mean BMI 37) to five weekly doses or placebo, with dose increases every four weeks (Roche, March 5, 2026). Key results:
- Up to 10.7% mean weight loss at week 42 versus 1.7% on placebo (efficacy estimand).
- Discontinuation for adverse events: 4.8% in the most effective arm versus 4.9% on placebo.
- No vomiting in the most effective arm; overall withdrawal was 8.4% on petrelintide versus 13.6% on placebo.
- Women lost considerably more weight than men, per Roche.
ZUPREME-2 (obesity plus type 2 diabetes)
Zealand reported topline results on October 7, 2026. In 220 adults with type 2 diabetes, petrelintide produced 7.4% to 9.2% weight loss at week 28 versus 2.0% on placebo, and lowered HbA1c by up to 0.65 points while placebo rose 0.23. GI-related discontinuation was 1.9% versus 1.7% on placebo (Zealand announcement).
Zealand said the Phase 3 program, ZUPREME-3, -4 and -5, has begun dosing and is expected to enroll about 7,000 people. A Phase 2 trial pairing petrelintide with Roche's GLP-1/GIP drug enicepatide (CT-388) was planned to start in the second half of 2026.
Cagrilintide on its own (Novo Nordisk)
CagriSema gets the headlines, but the REDEFINE 1 trial also had a cagrilintide-only arm. At 68 weeks, cagrilintide 2.4 mg produced 11.8% average weight loss versus 2.3% on placebo, or 11.5% versus 3.0% counting everyone regardless of adherence. About 31.6% lost at least 15% of their weight. Around 1.0% stopped because of nausea, versus 0.1% on placebo (Patient Care). Novo said it would move cagrilintide monotherapy into a Phase 3 program called RENEW, and the first trial, RENEW 1, started on November 5, 2025, with 300 participants (registry record).
The earlier-stage amylin field
| Drug | Company | Stage (latest we found) | What's known |
|---|---|---|---|
| MET-233i | Pfizer (acquired Metsera) | Phase 1 | Up to 8.4% placebo-adjusted loss at day 36 after five weekly doses; 19-day half-life suggests monthly dosing |
| AZD6234 | AstraZeneca | Phase 2 | Weekly; planned combination with AZD9550, a GLP-1/glucagon drug |
| GUBamy | AbbVie (licensed from Gubra) | Phase 1 | AbbVie paid $350 million for rights in 2025 |
Sources: Metsera, June 2025; Fierce Biotech; PharmaVoice. Pfizer's $10 billion Metsera deal is per PharmaVoice.
Novo's amycretin, a single molecule hitting both GLP-1 and amylin receptors, is a different design and is not covered here.
How to compare these drugs honestly
It is tempting to line up 20.1%, 11.8% and 10.7% and pick a winner. Don't, at least not yet. The trials differ in length (42, 48 and 68 weeks), in dose escalation, in how many people had diabetes, and in which estimand they headline. People with type 2 diabetes almost always lose less weight on any of these drugs, which is visible in ZUPREME-2.
The fair head-to-head questions, like eloralintide versus tirzepatide or petrelintide plus a GLP-1 versus a GLP-1 alone, have not been answered in published randomized trials as of October 2026.
Who these drugs might suit first
The trial designs hint at where each drug is aimed. Eloralintide's ENLIGHTEN-6 targets people who have plateaued on a weekly incretin, and Lilly has registered trials in sleep apnea and in knee osteoarthritis pain (ENLIGHTEN-4). Petrelintide has its own diabetes data in ZUPREME-2 and a planned pairing with a GLP-1/GIP drug. Cagrilintide's RENEW program tests it alone, separate from CagriSema.
That suggests three likely roles: an alternative for people who can't tolerate GLP-1 drugs, an add-on for people who plateau, and a building block for fixed combinations. Which role each drug wins will depend on Phase 3 results, not on Phase 2 headlines. Until then, the practical question for most patients is whether an approved GLP-1 option fits now, which is a conversation for your prescriber.
When could you actually get one?
The earliest Phase 3 primary completion date we found is eloralintide's ENLIGHTEN-1 at an estimated March 2028. Petrelintide's Phase 3 program only began dosing in 2026. Approval would come after those readouts and an FDA review, so an amylin-only prescription is unlikely before the late 2020s.
Starting treatment sooner?
See what FDA-approved GLP-1 medications cost from providers today.
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Frequently asked questions
Is any amylin drug approved for weight loss?
No. As of October 2026 no standalone amylin analog is approved for obesity. Pramlintide (Symlin) is approved only as a mealtime add-on for people with diabetes who use insulin.
How much weight did people lose on eloralintide?
In Lilly's 48-week Phase 2 trial, the 9 mg dose produced 20.1% average weight loss versus 0.4% on placebo. Lower doses produced 9.5% to 17.6%.
How does petrelintide compare with eloralintide?
Petrelintide's Phase 2 weight loss was lower, up to 10.7% at 42 weeks, but its side-effect dropout rate was similar to placebo. The trials differ in length and design, so a direct comparison isn't possible yet.
When could amylin drugs be available?
Eloralintide's first Phase 3 obesity trial has an estimated primary completion of March 2028, and petrelintide's Phase 3 program began dosing in 2026. Approval would follow those results and an FDA review.
Sources
- Eli Lilly: Eloralintide Phase 2 results (November 6, 2025)
- BioSpace: Lilly's amylin agonist headed to Phase III
- Registry record: ENLIGHTEN-1 (NCT07321886)
- Registry record: ENLIGHTEN-6 (NCT07392190)
- ClinicalTrials.gov: Eloralintide in obesity/overweight and type 2 diabetes (NCT07282600)
- EU CTIS: ENLIGHTEN-3 (sleep apnea)
- MedPath: ENLIGHTEN-4 (knee osteoarthritis pain, NCT07353931)
- Roche: Positive Phase II results for petrelintide (ZUPREME-1), March 5, 2026
- Zealand Pharma: ZUPREME-2 topline results, October 7, 2026
- Registry record: RENEW 1, cagrilintide Phase 3 (NCT07220642)
- Patient Care: Cagrilintide demonstrates 11.8% weight loss
- PharmaVoice: Amylin could reign supreme in the next wave of obesity drugs
- Metsera: Phase 1 data for MET-233i
- Fierce Biotech: AstraZeneca talks up obesity combos (AZD6234)
- Appleyard Lees: Amylin analogues for weight loss
- Symlin (pramlintide) prescribing information
- FDA: Concerns with unapproved GLP-1 drugs used for weight loss
Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.