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    Research 14 min readOct 25, 2026 Fact-checked

    Amylin Analogs and Agonists: Drugs, Trials, Status

    One amylin drug is approved and five are in phase 3 for obesity. Every analog and agonist we could verify in October 2026, with its phase and best result.

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    CoachLexi

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    Evidence notes from published research and trial registries. Educational information, not medical advice.

    Key Takeaway

    One amylin drug is approved and five are in phase 3 for obesity. Every analog and agonist we could verify in October 2026, with its phase and best result.

    Amylin analogs and agonists are drugs that copy or mimic amylin, a pancreatic hormone released with insulin at meals that slows the stomach and helps end eating. Only one is approved in the US: pramlintide (Symlin), approved in 2005 for people with type 1 or type 2 diabetes who use mealtime insulin, not for weight loss (FDA label).

    Five newer amylin drugs are in phase 3 for obesity: cagrilintide (Novo Nordisk), eloralintide (Lilly), petrelintide (Zealand and Roche), lenbelintide (AstraZeneca) and zenagamtide (Novo Nordisk), formerly amycretin. Two combinations sit beside them. CagriSema, cagrilintide plus semaglutide, is first in line, with an FDA decision expected by late 2026 (Novo), and Lilly's EloraTZP starts phase 3 in late 2026 (AMPLIFY-2). Any dose mentioned here is a trial dose, and apart from pramlintide, none of these drugs is approved.

    What amylin does

    Amylin is a 37-amino-acid peptide made by the same pancreatic beta cells that make insulin. The two hormones leave the cell together, at roughly 10 to 100 insulin molecules per amylin molecule, so amylin sits low between meals and climbs after food (Diabetes Therapy review, 2025). Most of its work happens in the hindbrain's area postrema, where it ends meals sooner, slows gastric emptying and damps the glucagon surge after eating (same review).

    Four facts explain the drug hunt (review):

    • It cuts intake and mostly takes fat. Preclinical work links amylin-driven weight loss to fat loss with relative preservation of lean mass.
    • Diabetes depletes it. Type 1 diabetes leaves people with almost none, and type 2 with too little.
    • Obesity does not. People with obesity tend to carry more amylin than lean people and still eat less when given extra. So the obesity drugs are not hormone replacement.
    • The natural peptide is a poor drug. It clears in under 20 minutes and clumps into amyloid fibrils. Pramlintide fixed the clumping with three prolines borrowed from rat amylin, but it still lasts only 20 to 45 minutes, hence injections at every main meal (review).

    Cagrilintide, petrelintide and eloralintide solve the timing problem with a fatty acid that binds albumin in the blood (Kruse 2021, Brændholt Olsen 2026, Briere 2025). That gives cagrilintide a half-life of about a week (Enebo 2021), petrelintide about 10 days (Brændholt Olsen 2026) and eloralintide close to two weeks (Briere 2025).

    The vocabulary: analog, agonist, SARA, DACRA

    Amylin receptors are built from the calcitonin receptor plus one of three RAMP proteins, giving AMY1, AMY2 and AMY3. The calcitonin receptor on its own mostly serves calcitonin, a calcium hormone (Briere 2025). How strongly a drug hits that bare calcitonin receptor is what splits the class.

    Term Meaning Examples
    Amylin analog A modified version of the amylin peptide itself Pramlintide, cagrilintide, eloralintide, petrelintide
    Amylin agonist Anything that switches on amylin receptors, peptide or not Every analog, plus nonpeptide drugs such as ACCG-2671
    SARA Selective amylin receptor agonist: favors amylin receptors over the calcitonin receptor Eloralintide, lenbelintide (AZD6234)
    DACRA Dual amylin and calcitonin receptor agonist Cagrilintide, petrelintide, ABBV-295, KBP-336
    Co-agonist One molecule acting on amylin and GLP-1 receptors Zenagamtide (amycretin)

    Labels follow a 2026 review by Alhazmi and le Roux, which warns they are loose, since every amylin receptor contains the calcitonin receptor.

    Amylin drugs in human trials, October 2026

    The table lists every clinical-stage program we could verify as of October 24, 2026.

    Drug (developer) Type Stage Best published weight result, with context Dosing in trials Our coverage
    Pramlintide, Symlin (AstraZeneca) Short-acting analog Approved 2005, diabetes only (label) 6.8% more than placebo at 12 months on 360 mcg twice daily, among 146 people still evaluable in a 411-person obesity trial (Smith 2008) Before major meals, two or three times a day None
    Cagrilintide (Novo Nordisk) DACRA Phase 3, RENEW, since November 2025 (NCT07220642) 11.8% vs 2.3% at 68 weeks on 2.4 mg, adults without diabetes, trial product estimand (Novo) Weekly Compound page
    CagriSema (Novo Nordisk) Cagrilintide plus semaglutide FDA submission December 2025 (Novo) 20.4% vs 3.0% at 68 weeks on 2.4 mg of each, counting everyone randomized (Garvey 2025) Weekly Compound page
    Eloralintide (Eli Lilly) SARA, favors AMY1 Phase 3, five ENLIGHTEN trials (NCT07321886) 20.1% vs 0.4% at 48 weeks on 9 mg, 263 US adults, efficacy estimand (Lilly) Weekly Compound page, phase 2 review, phase 3 trials, vs retatrutide
    EloraTZP (Eli Lilly) Eloralintide plus tirzepatide Phase 3, AMPLIFY, from late 2026 (NCT07881432) 23.3% vs 3.0% at 48 weeks on eloralintide 9 mg with tirzepatide 15 mg, 367 adults with type 2 diabetes, efficacy estimand; tirzepatide alone 14.8% (Lilly) Weekly Trial results
    Petrelintide (Zealand, Roche) DACRA Phase 3, ZUPREME-3 to 5, since September 30, 2026 (NCT07843498) 7.9% to 9.8% vs 1.7% at 28 weeks across five doses, up to 10.7% by week 42, 493 adults, efficacy estimand (ZUPREME-1) Weekly ZUPREME-1 review
    Zenagamtide, formerly amycretin (Novo Nordisk) Amylin and GLP-1 co-agonist Phase 3, AMAZE, since February 2026 (NCT07339423) 24.3% vs 1.1% at 36 weeks on 60 mg, top dose group of a 125-person phase 1b/2a study (Dahl 2025) Weekly injection or daily tablet Trial review
    Lenbelintide, AZD6234 (AstraZeneca) SARA Phase 3, SELENE 1 to 3, since August 2026 (NCT07784725) 3.8% from baseline by day 5 after one 2.7 mg dose in a 54-person phase 1; half-life about 4 days (review) Weekly None
    KBP-336 (KeyBioscience) DACRA Phase 2 in obesity with knee osteoarthritis, 600 people, since January 2025 (NCT06833749) None we found Weekly None
    ABBV-295, formerly GUB014295 (AbbVie) DACRA Phase 2 since August 2026 (NCT07752979) 9.79% vs 0.26% at 12 weeks in the best weekly cohort of a 76-person phase 1, mostly men, mean BMI under 30 (AbbVie) Weekly, every other week and monthly None
    MET-233i (Pfizer, from Metsera) Long-acting analog Phase 1 results reported (Pfizer); possibly the amylin drug in Pfizer's phase 2b SOLIS-1 (note below) Up to 8.4% more than placebo at day 36 after five weekly 1.2 mg doses, 80-person phase 1; half-life 19 days (Metsera) Weekly in phase 1, built for monthly None
    ACCG-2671 (Structure Therapeutics) Oral nonpeptide DACRA Phase 1/2a since December 2025 (NCT07815678) 3.3% by day 24 after one 10 mg dose, 31 healthy adults without obesity; half-life about 6 days (Structure, via RTTNews) Oral, daily or weekly None
    VK3019 (Viking Therapeutics) Amylin and calcitonin receptor agonist Phase 1, single doses, since July 2026 (NCT07846033) None we found Injection None
    ASC36 (Ascletis) Amylin receptor agonist Phase 1 as an injection and as a tablet, since September and October 2026 (NCT07893093, NCT07893106) None we found Injection or tablet None
    VRB-103 (Verdiva Bio) Oral amylin analog Phase 1, alone and with oral ecnoglutide, since July 2026 (NCT07628127) None we found Tablet None
    NN1213 (Novo Nordisk) Analog Phase 1 (Bhattachar 2026) None we found Not disclosed None

    The results column is not a league table. The numbers span 5 days to 68 weeks and several estimands. ABBV-295's 12-week figure came from a mostly male group with a mean BMI under 30; eloralintide's 48-week figure from a group that was 78% women with a mean BMI of 39.1 (Billings 2025). Those trials were never designed to be compared.

    Some names here are new. Zenagamtide is amycretin's new name (Lancet 2026), and lenbelintide is AZD6234's, per SELENE 3 (NCT07776509). Pfizer's are murkier. Its 940-person SOLIS-1 phase 2b, begun in May 2026, pairs PF-08653945, tagged in its keywords as an amylin DACRA, with PF-08653944 (NCT07575932), listed in VESPER-5 as MET097, Metsera's GLP-1 drug (NCT07400653). The registry never says which drug PF-08653945 is; MET-233i is the amylin drug Pfizer bought with Metsera.

    Selective or dual: does the receptor profile matter?

    The case for selectivity is mostly preclinical. A 2026 review argues that calcitonin receptor engagement, along with drug exposure and the brain circuits recruited, may decide whether eating less feels like fullness or like malaise (Fischer and Borner 2026). In Lilly's rat experiments, the selective eloralintide caused less taste avoidance than the dual cagrilintide at a similar cut in food intake (Briere 2025).

    The case for dual agonists is partly theoretical too. The calcitonin receptor matters for bone. A pramlintide infusion lowered CTX-1, a marker of bone breakdown (Alhazmi and le Roux 2026), and single doses of the oral DACRA ACCG-2671 cut it by about 60% (Structure, via RTTNews). That hints at bone protection during weight loss; no trial has shown it.

    Human data do not settle it. Petrelintide, a dual agonist, produced nausea in 20% of people against 6% on placebo, mostly mild and during dose escalation (ZUPREME-1). Eloralintide, the only selective agonist with published phase 2 data, produced nausea in 18 of 28 people when started at 6 mg and in 13 of 52 when stepped up over eight weeks, against 7 of 53 on placebo (NCT06230523). In these trials, how fast the dose rises looks at least as important as which receptors the drug hits. No trial has tested a selective against a dual agonist; our eloralintide vs cagrilintide comparison covers the closest pair.

    How companies are pairing amylin with incretins

    Amylin and GLP-1 drugs act through partly separate brain circuits (Alhazmi and le Roux 2026), so companies test amylin drugs both alone and as GLP-1 partners.

    The most advanced route is two drugs on one schedule. CagriSema pairs cagrilintide with semaglutide. Beyond REDEFINE 1, it lost 13.7% against 3.4% on placebo over 68 weeks in adults with type 2 diabetes (Davies 2025). It fell short of non-inferiority against tirzepatide 15 mg in REDEFINE 4, though, at 20.2% versus 23.6% after 84 weeks counting everyone (Novo). Lilly's EloraTZP takes the same route with tirzepatide and is headed for phase 3 as a co-formulated product (Lilly).

    Novo's other bet puts everything in one molecule. Zenagamtide combines amylin, calcitonin and GLP-1 receptor activity in a single peptide, given as a weekly injection or a daily tablet (injection trial, tablet trial). Phase 3 began with AMAZE 1, 1,150 people, in February 2026 (NCT07339423, registered as NNC0487-0111), and includes AMAZE 7 against semaglutide over 84 weeks (NCT07668414), AMAZE 9 for the tablet (NCT07720271) and AMBIENCE, an 8,500-person heart outcomes trial (NCT07861100).

    A third route adds an amylin drug for people already on an incretin. ENLIGHTEN-6 adds eloralintide for 900 people still living with obesity on a weekly incretin (NCT07392190), and SELENE 3 tests lenbelintide as an add-on in 500 people (NCT07776509).

    Then there are the newer pairings, all in phase 2. Roche's ZYNERGY trial combines petrelintide with enicepatide, Roche's GLP-1 and GIP agonist, in 486 people (NCT07589686, Roche). AstraZeneca's ASCEND paired AZD6234 with AZD9550, a GLP-1 and glucagon agonist, in 377 people and finished in May 2026 without posted results (NCT06862791, review). Lilly is testing eloralintide with macupatide (LY3532226) in two phase 2 trials (NCT07215559, NCT07589608).

    What the next trials have to answer

    • Does selectivity matter in people? Every argument above rests on rats or cross-trial comparisons.
    • What do these drugs do to the heart? Amylin drugs appear to lower pulse; on 12 mg of eloralintide, pulse fell 14.4 beats a minute over 12 weeks (Bhattachar 2026). A 2025 Lancet paper also raised the possibility that amylin drugs activate the renin-angiotensin system (Muskiet 2025). Outcome trials should answer more: REDEFINE 3 for CagriSema in 7,101 people, primary completion September 2027 (NCT05669755), and AMBIENCE for zenagamtide (NCT07861100).
    • What happens after people stop? REDEFINE 1 included a two-year off-treatment extension scheduled to end on October 19, 2026 (post hoc). We found no results from it as of October 24; when they appear, they should show how much weight returns after CagriSema stops.
    • Can one shot last a month? MET-233i's 19-day half-life and ABBV-295's monthly cohorts make a monthly amylin shot plausible, though untested in long trials.
    • Who benefits most? Women on CagriSema lost 25.0% at 68 weeks in a post hoc analysis (Pharmacy Times), above the trial's 22.7% average (post hoc), though the analysis did not formally test a sex effect.

    Sources

    Frequently asked

    GLP-1 is an incretin hormone from the gut that raises insulin release when blood sugar is high, slows the stomach and reduces eating (Müller 2019). Amylin comes from the pancreatic beta cells with insulin, does not stimulate insulin release, and works mainly through hindbrain amylin receptors to end meals and restrain glucagon after eating (review). Their effects only partly overlap, which is why companies combine them.

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    Evidence notes from published research and trial registries. Educational information, not medical advice.