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GLP-1 Alternatives: Amylin and Other Non-GLP-1 Pathways

The main alternatives to GLP-1 drugs work through amylin, glucagon, GIP, activin receptors or older brain pathways. Eloralintide, cagrilintide, petrelintide, survodutide, mazdutide, bimagrumab, Qsymia and Contrave compared by pathway, status in November 2026 and best trial result.

Updated 8 November 2026 10 min read 46 primary sourcesHow we research

Key facts

  • Amylin agonists are the main pathway being developed apart from GLP-1. The best amylin-only result so far is 20.1% weight loss at 48 weeks with eloralintide 9 mg in phase 2.[1]
  • Only a few non-GLP-1 weight drugs are FDA approved: Qsymia (2012), Contrave (2014) and, for rare genetic obesity only, Imcivree (2020).[46]
  • Glucagon co-agonists such as survodutide (16.6% at 76 weeks) and mazdutide still include GLP-1. They add a second pathway rather than replace it.[37][39]
  • Bimagrumab, an activin receptor antibody, cut weight by 10.8% at 72 weeks on its own, mostly as fat, and is still in phase 2.[32]
  • Every amylin, glucagon and activin drug on this page except pramlintide is investigational in the US. Mazdutide is approved only in China.[40][37]

What Are the Alternatives to GLP-1 Drugs?

The alternatives to GLP-1 drugs fall into four groups: amylin agonists (best result 20.1% at 48 weeks), activin receptor blockers (10.8% at 72 weeks), older approved drugs that act on other brain pathways (up to 10.9% at 56 weeks), and drugs that add glucagon, GIP or amylin to GLP-1.[1][32][43]

Status as of November 2026. Best result is mean body weight change in the drug’s largest or longest reported trial. Trials differ in length, population and estimand, so the numbers are not directly comparable.
DrugDeveloperPathwayStatus (Nov 2026)Best reported result
EloralintideEli LillySelective amylin receptor agonist (no GLP-1)Phase 3 (ENLIGHTEN)[6]-20.1% at 48 wk, 9 mg, phase 2[1]
CagrilintideNovo NordiskAmylin and calcitonin receptor agonist (no GLP-1)Investigational; only filed as part of CagriSema[15]-11.8% at 68 wk, 2.4 mg, REDEFINE 1[12]
PetrelintideZealand Pharma with RocheAmylin and calcitonin receptor agonist (no GLP-1)Phase 3 (ZUPREME)[19]Up to -10.7% at 42 wk, phase 2[17]
Pramlintide (Symlin)AstraZeneca (label holder)Amylin analogue (no GLP-1)FDA approved 2005, for diabetes only[23]-0.8 to -1.6 kg in type 1 diabetes trials[22]
BimagrumabEli LillyActivin type II receptor antibody (no GLP-1)Phase 2[34]-10.8% at 72 wk, 30 mg/kg IV, BELIEVE[32]
Phentermine/topiramate (Qsymia)VivusSympathomimetic plus topiramate (no GLP-1)FDA approved 2012[46]-10.9% at 56 wk, 15/92 mg[43]
Naltrexone/bupropion (Contrave)NalpropionOpioid antagonist plus bupropion (no GLP-1)FDA approved 2014[46]-5.4% at 56 wk, COR-I[44]
Setmelanotide (Imcivree)Rhythm PharmaceuticalsMC4 receptor agonist (no GLP-1)FDA approved 2020, rare genetic or hypothalamic obesity only[46][45]Not comparable: specific rare conditions
CagriSemaNovo NordiskAmylin plus GLP-1Submitted to FDA Dec 2025[15]-20.4% at 68 wk, REDEFINE 1[13]
Zenagamtide (amycretin)Novo NordiskOne molecule on GLP-1 and amylin receptorsPhase 3 (AMAZE)[26]-24.3% at 36 wk, 60 mg, phase 1b/2a[24]
SurvodutideBoehringer Ingelheim (licensed from Zealand)Glucagon plus GLP-1Phase 3, not approved[37]-16.6% at 76 wk, SYNCHRONIZE-1[37]
MazdutideInnovent (China licence from Lilly)Glucagon plus GLP-1Approved in China, Jun 2025[40]-14.0% at 48 wk, 6 mg, GLORY-1[39]
RetatrutideEli LillyGIP, GLP-1 and glucagonPhase 3; FDA filing planned Q1 2027[28]-28.3% at 80 wk, 12 mg, TRIUMPH-1[27]
MariTideAmgenGLP-1 agonist plus GIP receptor blockerPhase 3 (MARITIME)[42]Up to -16.2% at 52 wk, phase 2[41]

For reference, semaglutide 2.4 mg (Wegovy), a GLP-1 drug, cut weight by 14.9% at 68 weeks in STEP 1, and tirzepatide (Zepbound), which acts on GIP and GLP-1, by 20.9% at 72 weeks in SURMOUNT-1.[29][30] Semaglutide works by activating the GLP-1 receptor, a natural regulator of appetite and calorie intake.[31] The drugs in the top half of the table do not touch that receptor at all.

This guide summarises published research. It is not medical advice, and most of the drugs listed are not approved for weight management anywhere. DBR Labs supplies eloralintide for laboratory research only and does not sell any of the other drugs named here.

Amylin Agonists: The Main Non-GLP-1 Pathway

Amylin agonists are the largest group of non-GLP-1 drugs in development, and four have human data: eloralintide (20.1% at 48 weeks), cagrilintide (11.8% at 68 weeks), petrelintide (up to 10.7% at 42 weeks) and the approved diabetes drug pramlintide.[1][12][17][22]

Amylin is a 37-amino-acid hormone made by the beta cells of the pancreas.[20] It is released with insulin after meals, slows stomach emptying, suppresses glucagon and reduces food intake through the brain.[22] Its best-studied effect is making people feel full sooner, so meals get smaller.[21] This is a separate hormone system from GLP-1. For the biology, see what is amylin.

  • Eloralintide (Lilly). A once-weekly amylin agonist designed to favour the AMY1 receptor, about 12 times more potent there than at the calcitonin receptor. Full profile: what is eloralintide.[4][5]
  • Cagrilintide (Novo Nordisk). A once-weekly analogue that activates amylin and calcitonin receptors with similar potency, with a half-life of 159 to 195 hours. See what is cagrilintide.[4][11]
  • Petrelintide (Zealand Pharma and Roche). A once-weekly human amylin analogue built to stay stable at neutral pH, now in phase 3; ZUPREME-3 alone plans 3,900 people. See what is petrelintide.[18][19]
  • Pramlintide (Symlin). The only approved amylin drug, approved in 2005 for people with diabetes who use mealtime insulin. It is injected before each main meal and is not approved for weight loss. See what is pramlintide.[23][22]

Nausea is still the main side effect of amylin drugs. Rates were 20% to 47% across cagrilintide phase 2 doses (placebo 18%), 20% on petrelintide in ZUPREME-1 (placebo 6%) and 11% to 64% across eloralintide arms (placebo 14%).[10][17][2]

Where Eloralintide Fits Among GLP-1 Alternatives

Eloralintide gave the largest reported weight loss for an amylin-only drug, 20.1% at 48 weeks on 9 mg against 0.4% on placebo, but that came from a 263-person phase 2 trial and the drug is not approved anywhere.[1][2]

Eloralintide phase 2, 48 weeks, adults with obesity or overweight without type 2 diabetes. Mean change is Lilly’s efficacy estimand (had everyone stayed on treatment); the 10% column is from the ClinicalTrials.gov posted results.
ArmMean weight changeReached 10% or more
Placebo-0.4%[1]12.9%[3]
1 mg-9.5%53.3%
3 mg-12.4%60.5%
6 mg-17.6%76.6%
9 mg-20.1%82.3%
6 to 9 mg escalation-19.9%91.1%
  • What supports it. The result came without any GLP-1 activity, and Lilly says gastrointestinal symptoms and fatigue at 1 mg and 3 mg were similar to placebo.[1]
  • What limits it. Nausea reached 64% in the 6 mg arm and fatigue up to 46%, and some arms had only 24 to 28 people.[2]
  • What comes next. The ENLIGHTEN phase 3 programme is recruiting. ENLIGHTEN-1, in obesity without diabetes, has 1,980 people and an estimated primary completion in March 2028.[6]
  • Combination. Lilly is also testing eloralintide with tirzepatide (EloraTZP), which gave 23.3% weight loss at 48 weeks in people with type 2 diabetes in phase 2b.[8]

There is no head-to-head trial against a GLP-1 drug yet. The closest comparison is eloralintide vs semaglutide, which sets the phase 2 data against STEP 1 and explains why the estimands differ.

Amylin Combined With GLP-1

Adding amylin to GLP-1 has given some of the largest results so far: 20.4% at 68 weeks for CagriSema and 24.3% at 36 weeks for zenagamtide 60 mg, against 3.0% and 1.1% on placebo.[13][24]

  • CagriSema is a once-weekly fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg. Novo Nordisk submitted it to the US FDA in December 2025, and it is not yet approved.[13][15][16]
  • Zenagamtide, formerly amycretin, is a single molecule that activates GLP-1, amylin and calcitonin receptors. Its phase 3 AMAZE programme started in 2026. See amycretin (zenagamtide).[25][26]
  • EloraTZP pairs eloralintide with tirzepatide. Lilly planned a co-formulated phase 3 programme from Q4 2026, and AMPLIFY-1 lists 2,115 people with a 100-week primary endpoint.[8][9]
  • Petrelintide is also being developed by Roche in combination with its incretin drug CT-388.[18]

These are not alternatives to GLP-1 in the strict sense, because they still contain it. They suit the searcher who wants a different or stronger mechanism rather than one without GLP-1.

Glucagon and GIP Co-Agonists

Glucagon and GIP co-agonists add a second hormone to GLP-1, and the strongest result is 28.3% at 80 weeks for retatrutide 12 mg, which acts on GIP, GLP-1 and glucagon receptors.[27]

Separate trials, not directly comparable. Treatment-regimen or treatment-policy figures count people who stopped treatment; efficacy figures assume everyone stayed on it.
DrugPathwaysTrialResult
SurvodutideGlucagon + GLP-1SYNCHRONIZE-1, 725 people, 76 wk-13.0% (6.0 mg, treatment-regimen) vs -5.4% placebo[35]; up to -16.6% efficacy estimand[37]
SurvodutideGlucagon + GLP-1SYNCHRONIZE-2, type 2 diabetes, 752 people, 76 wk-9.8% (6.0 mg) vs -3.9% placebo[36]
MazdutideGlucagon + GLP-1GLORY-1, China, 610 people, 48 wk-14.0% (6 mg) vs +0.3% placebo[39]
RetatrutideGIP + GLP-1 + glucagonTRIUMPH-1, 2,339 people, 80 wk-28.3% (12 mg, efficacy) vs -2.2% placebo[27]
MariTideGLP-1 agonist + GIP receptor blockerPhase 2, 465 people with obesity, 52 wk-12.3% to -16.2% vs -2.5% placebo[41]
  • Why glucagon. Boehringer Ingelheim says survodutide’s GLP-1 activity reduces appetite, while glucagon activity is thought to act directly on the liver to reduce liver fat.[37] In a SYNCHRONIZE-1 substudy, liver fat fell by up to 63.1%.[38]
  • Side effects. Gastrointestinal events affected 80.9% to 89.7% of people on survodutide against 47.9% on placebo in SYNCHRONIZE-1.[35]
  • Status. Survodutide is not approved anywhere.[37] Mazdutide was approved in China in June 2025, which Innovent says makes it the first glucagon/GLP-1 drug approved for weight loss.[40] Lilly plans to submit retatrutide to the FDA in Q1 2027.[28] Amgen reports no phase 3 MariTide results yet.[42]
  • Dosing interval. MariTide was given every 4 or 8 weeks in phase 2, not weekly.[41]

For how retatrutide compares with an amylin drug, see eloralintide vs retatrutide.

Activin Receptor Blockers: Bimagrumab

Bimagrumab, an antibody that blocks activin type II receptors, cut weight by 10.8% at 72 weeks on its own and by 22.1% with semaglutide 2.4 mg, against 15.7% for semaglutide alone, in the 507-person BELIEVE trial.[32]

  • How it differs. Bimagrumab is meant to reduce body and visceral fat while promoting muscle growth. It has no GLP-1 activity and was given as an intravenous infusion every 12 weeks.[32]
  • Fat, not muscle. At 72 weeks, fat mass fell by 28.5% on bimagrumab 30 mg/kg, similar to 27.8% on semaglutide 2.4 mg, and by 45.7% with the combination.[32] In an earlier type 2 diabetes trial, fat mass fell by 20.5% while lean mass rose by 3.6% over 48 weeks.[33]
  • Side effects. Muscle spasms, diarrhoea and acne were common, and stopping because of adverse events was higher on bimagrumab alone (14.0% to 21.4%) than on semaglutide (3.6% to 8.8%) or placebo (3.6%).[32]
  • Status. Still in phase 2. Lilly is now testing it with tirzepatide in a 252-person trial.[34]

Approved Non-GLP-1 Weight Loss Drugs

Two FDA-approved weight loss drugs for general obesity work without GLP-1: phentermine/topiramate (Qsymia), with 10.9% weight loss at 56 weeks on the top dose, and naltrexone/bupropion (Contrave), with 5.4% at 56 weeks.[43][44]

From the FDA labels. Placebo-group figures in brackets.
DrugFDA approvalHow it worksLabel trial result
Qsymia (phentermine/topiramate)Jul 2012[46]Phentermine releases catecholamines in the hypothalamus to reduce appetite; combined with topiramate[43]-10.9% at 56 wk on 15/92 mg (-1.6%)[43]
Contrave (naltrexone/bupropion)Sep 2014[46]Nonclinical studies suggest it acts on the hypothalamus and the brain’s reward system[44]-5.4% at 56 wk in COR-I (-1.3%)[44]
Imcivree (setmelanotide)Nov 2020[46]MC4 receptor agonist[45]Only for named rare genetic forms of obesity and acquired hypothalamic obesity[45]
Symlin (pramlintide)Mar 2005[23]Amylin analogue[22]Diabetes only; not approved for weight loss[22]

Both Qsymia and Contrave are labelled for use alongside a reduced-calorie diet and more physical activity.[43][44] Their results are smaller than the newer drugs on this page, and many people stopped treatment in the trials: 49.2% of the Contrave group and 50.1% of the placebo group in COR-I stopped the study drug.[44]

Is Amylin Better Than GLP-1?

Not on current evidence: in REDEFINE 1, the only trial to test both side by side, cagrilintide alone gave 11.8% weight loss at 68 weeks against 16.1% for semaglutide, though with less nausea (23.8% vs 43.7%).[12][14]

Amylin drugs may suit different research questions rather than replace GLP-1. Eloralintide’s 20.1% at 48 weeks is higher than semaglutide’s 14.9% at 68 weeks in STEP 1, but those are separate trials with different lengths and estimands.[1][29] Lilly is running ENLIGHTEN-6 in people who still have obesity while on a weekly incretin, which will test amylin as an add-on rather than a swap.[7] The strongest results so far come from combining both pathways, as with CagriSema and EloraTZP.[13][8]

Frequently Asked Questions

What is the best alternative to GLP-1?

There is no single best one. Among drugs with no GLP-1 activity, eloralintide gave the largest reported weight loss (20.1% at 48 weeks in phase 2), but it is still investigational. Among approved non-GLP-1 drugs, Qsymia gave 10.9% at 56 weeks in its label trial.

Is there a non-GLP-1 weight loss drug?

Yes. Qsymia (phentermine/topiramate, approved 2012) and Contrave (naltrexone/bupropion, approved 2014) are FDA-approved and do not act on GLP-1. Imcivree is approved only for rare genetic obesity. Amylin agonists such as eloralintide, cagrilintide and petrelintide, and the antibody bimagrumab, are still in trials.

Is amylin better than GLP-1?

Not on current evidence. In REDEFINE 1, cagrilintide alone gave 11.8% weight loss at 68 weeks against 16.1% for semaglutide, with less nausea. Eloralintide’s 20.1% at 48 weeks came from a separate, smaller trial, and no head-to-head trial against a GLP-1 drug has reported.

What are natural alternatives to GLP-1?

There is no approved non-drug equivalent. Your body makes GLP-1 and amylin itself, and amylin is released with insulin after meals, but none of the trials cited here shows a food or supplement matching these drugs. The approved drugs are all labelled for use alongside a reduced-calorie diet and more physical activity.

Is eloralintide a GLP-1?

No. Eloralintide is a selective amylin receptor agonist with no GLP-1 activity. It mimics amylin, a different hormone released with insulin, and Lilly is also testing it combined with the GIP/GLP-1 drug tirzepatide as EloraTZP.

Are any GLP-1 alternatives approved?

In the US, Qsymia, Contrave and Imcivree are approved for weight management, and pramlintide is approved for diabetes only. Mazdutide, a glucagon/GLP-1 drug, is approved in China. Eloralintide, cagrilintide, petrelintide, survodutide, bimagrumab and MariTide are not approved anywhere.

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For research use only. Not for human or veterinary consumption. This guide summarises published research for information only. It is not medical advice and does not describe any use of products sold on this site.

Related Guides

Basics

What Is Amylin? The Hormone Behind Eloralintide and Cagrilintide

Amylin is a 37-amino-acid hormone released with insulin that slows stomach emptying, curbs glucagon and signals fullness. How amylin analogues work, from pramlintide to eloralintide.

Comparisons

Eloralintide vs Semaglutide (Wegovy): Amylin vs GLP-1

Eloralintide vs semaglutide: Lilly’s amylin agonist reached 20.1% weight loss at 48 weeks in phase 2, against 14.9% at 68 weeks for Wegovy in STEP 1. Mechanism, nausea and dosing compared.

Comparisons

Amycretin (Zenagamtide): Trial Results and How It Compares to Eloralintide

Amycretin, now named zenagamtide, is Novo Nordisk’s single molecule acting on GLP-1 and amylin receptors: 24.3% weight loss at 36 weeks in phase 1b/2a, a daily pill version, and phase 3 under way.