Eloralintide vs Cagrilintide: Comparing the Next Generation of Amylin Analogs
Eloralintide's Phase 2 trial hit 20% weight loss at 48 weeks; cagrilintide's CagriSema hit 20.4% at 68 weeks. Compare amylin mechanisms and 2026 data.
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Eloralintide and cagrilintide are two amylin-receptor-targeted peptides advancing through late-stage obesity research, each representing a different strategic bet on how amylin signaling can be used to treat obesity — one as a standalone selective amylin receptor agonist, the other as the amylin half of a fixed-dose GLP-1 combination. Both have posted substantial Phase 2/3 weight-loss data in 2025 and 2026, but their development paths, receptor pharmacology, and regulatory trajectories diverge in ways that matter for anyone tracking the amylin-analog research landscape.
Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.
Quick Answer: Eloralintide is Eli Lilly's selective amylin receptor agonist, tested largely as a standalone therapy and producing up to 20% weight loss at 48 weeks in a Phase 2 trial, while cagrilintide is Novo Nordisk's amylin analogue studied primarily in combination with semaglutide as CagriSema, which produced 20.4% weight loss at 68 weeks in Phase 3 — the core difference is monotherapy-first development versus combination-first development.
TL;DR:
- Eloralintide (LY3841136, Eli Lilly) is a selective amylin receptor agonist studied as a standalone therapy and as an add-on to existing incretins; a multi-arm Phase 3 program is underway.
- Cagrilintide (Novo Nordisk) is developed primarily as the amylin component of CagriSema (cagrilintide + semaglutide); an NDA was submitted to the FDA in December 2025.
- Both act on amylin receptor subtypes to engage central satiety pathways, independent of or complementary to GLP-1 receptor signaling.
- Cagrilintide's Phase 3 REDEFINE 1 data (20.4% weight loss) reflects combination therapy; eloralintide's Phase 2 data (up to 20% weight loss) reflects monotherapy — direct efficacy comparison requires caution.
- Neither compound holds FDA approval as of mid-2026; both remain investigational and are not currently eligible for 503A compounding.
Eloralintide: mechanism and evidence base
Eloralintide (development code LY3841136) is a selective amylin receptor agonist developed by Eli Lilly. Full profile: /library/eloralintide/. Unlike GLP-1-pathway compounds such as semaglutide and tirzepatide, eloralintide activates amylin receptor signaling without engaging GLP-1 or GIP receptors, positioning it as a mechanistically independent option that researchers have investigated both as a monotherapy and as an add-on for patients whose weight loss plateaus on incretin-class therapy.
In a Phase 2, double-blind, randomized, placebo-controlled trial published in the Lancet (December 2025; PMID 41207310; NCT06230523), 263 adults with obesity or overweight and at least one weight-related comorbidity were randomized across six eloralintide dose and titration arms (1 mg, 3 mg, 6 mg, 9 mg, 6–9 mg, 3–9 mg) or placebo for 48 weeks. Mean bodyweight reduction ranged from 9% (1 mg) to 20% (9 mg and 6–9 mg arms) versus 0.4% with placebo, with no clear plateau observed at the higher doses. Nausea and fatigue were the most common adverse events, generally dose-dependent.
Based on this data, Lilly advanced eloralintide into a Phase 3 program spanning several distinct research questions: type 2 diabetes (NCT07282600), obstructive sleep apnea with obesity (NCT07369011), combination with the GIP-agonist macupatide (NCT07215559), and use as an add-on for patients with persistent obesity or overweight already on a weekly incretin (NCT07392190, ENLIGHTEN-6). Researchers can track enrollment and status for these trials using the clinical trial tracker.
Cagrilintide: mechanism and evidence base
Cagrilintide is a long-acting synthetic amylin analogue developed by Novo Nordisk. Full profile: /library/cagrilintide/. It binds amylin receptor subtypes AMY1R, AMY2R, and AMY3R — heteromeric complexes of the calcitonin receptor and receptor activity-modifying proteins — engaging both homeostatic (hypothalamic) and hedonic (mesolimbic) satiety pathways. Structurally, cagrilintide carries stabilizing mutations that prevent fibril formation and an N-terminally linked C20 fatty acid that extends its half-life to roughly 159–195 hours, enabling once-weekly dosing.
Cagrilintide has been studied predominantly in combination with semaglutide as CagriSema, where the amylin and incretin pathways are proposed to act synergistically. In the Phase 3 REDEFINE 1 trial (New England Journal of Medicine; PMID 40544432; 2026), once-weekly cagrilintide 2.4 mg co-administered with semaglutide 2.4 mg produced a mean body weight reduction of 20.4% at 68 weeks versus 3.0% with placebo in adults with overweight or obesity without type 2 diabetes. Sixty percent of participants achieved at least 20% weight loss, and 23% lost at least 30%. Gastrointestinal adverse events occurred in 79.6% of the CagriSema group versus 39.9% with placebo, predominantly mild-to-moderate and transient. Novo Nordisk submitted a New Drug Application for CagriSema in December 2025, with a regulatory decision expected in late 2026.
Earlier Phase 2 dose-escalation research also examined cagrilintide as a monotherapy, where it demonstrated dose-dependent weight reduction, though most of the compound's later-stage research program has centered on the combination formulation rather than standalone use. In that Phase 2 dose-escalation work, cagrilintide combined with semaglutide 2.4 mg produced 17.1% weight loss versus 9.8% for semaglutide monotherapy at week 20 — an early signal of the additive effect later confirmed at Phase 3 scale in REDEFINE 1. A companion trial, Phase 3 REDEFINE 2, extended the CagriSema research program into adults with type 2 diabetes, reporting 15.7% weight loss alongside significantly improved HbA1c compared with active comparators, indicating the combination's effects extend to a metabolically distinct population beyond the REDEFINE 1 cohort.
Side-by-side comparison
| Eloralintide | Cagrilintide | |
|---|---|---|
| Developer | Eli Lilly | Novo Nordisk |
| Mechanism | Selective amylin receptor agonist | Amylin receptor agonist (AMY1R/AMY2R/AMY3R), typically paired with semaglutide |
| Primary study design | Monotherapy (Phase 2), incretin add-on (Phase 3) | Combination therapy with semaglutide (CagriSema) |
| Key trial | Phase 2 (Lancet, Dec 2025), n=263, 48 weeks | Phase 3 REDEFINE 1 (NEJM, 2026), 68 weeks |
| Reported weight loss | 9–20% across dose arms vs 0.4% placebo | 20.4% (CagriSema) vs 3.0% placebo |
| Dosing | Once-weekly subcutaneous | Once-weekly subcutaneous (~159–195 hr half-life) |
| Regulatory status (mid-2026) | Investigational, Phase 3 ongoing | Investigational; NDA submitted Dec 2025 |
| 503A compounding status | Not 503A eligible | Under review |
Differential research applications
The two programs answer somewhat different research questions. Eloralintide's monotherapy design isolates the amylin-receptor contribution to weight loss independent of GLP-1 signaling, which is why Lilly's Phase 3 program includes an explicit add-on trial (ENLIGHTEN-6) testing eloralintide layered onto an existing incretin — a design suited to researchers studying whether amylin agonism can rescue plateaued weight loss on incretin therapy. Cagrilintide's program, by contrast, was built around the combination hypothesis from the outset: REDEFINE 1 tests the amylin-GLP-1 combination directly rather than isolating cagrilintide's standalone contribution, which limits how cleanly its efficacy can be attributed to the amylin component alone.
For researchers comparing dosing schedules and projected washout periods across both compounds and their reference incretins, the half-life comparison chart provides a side-by-side view alongside retatrutide and other pipeline compounds.
The adverse-event profiles also point to different research considerations. Eloralintide's Phase 2 program reported nausea and fatigue as the dominant dose-dependent effects, generally consistent with the gastrointestinal tolerability profile seen across amylin- and incretin-pathway peptides. Cagrilintide's combination arm in REDEFINE 1 reported a notably higher gastrointestinal adverse-event rate (79.6% versus 39.9% placebo), which researchers studying tolerability trade-offs in combination regimens may want to weigh against the magnitude of the additive weight-loss effect. Because eloralintide has, to date, been tested predominantly as a monotherapy while cagrilintide's flagship data comes from a fixed-dose combination, isolating whether cagrilintide alone would produce a materially different tolerability signal remains an open question in the published record.
Regulatory and compounding status
As of mid-2026, neither compound holds FDA approval. Eloralintide remains in an active Phase 3 program with no NDA filed. Cagrilintide, as the amylin component of CagriSema, has an NDA under FDA review following its December 2025 submission, with a decision anticipated in late 2026 — a regulatory milestone eloralintide has not yet reached as a standalone or combination product. Both compounds are classified as investigational biologic peptides and are not currently eligible for 503A bulk drug substance compounding; cagrilintide's compounding status is listed as under review pending federal determinations that typically follow FDA approval decisions.
This regulatory gap is itself a research-relevant data point. Because cagrilintide's review is tied to the fixed-dose CagriSema combination rather than cagrilintide as a standalone molecule, an FDA decision in late 2026 would establish a regulatory pathway for the combination product specifically — it would not, on its own, establish cagrilintide monotherapy as an approved or 503A-eligible substance. Eloralintide's multi-arm Phase 3 program, spanning type 2 diabetes, obstructive sleep apnea, and both combination and add-on regimens, will generate a broader evidentiary base before any regulatory filing, which may extend its timeline relative to cagrilintide's combination-first strategy even as it produces data across a wider range of study populations.
Cited studies
- PMID 41207310 — "Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial." (The Lancet, 2025). https://doi.org/10.1016/S0140-6736(25)02155-5
- PMID 40544432 — "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)." (New England Journal of Medicine, 2026). https://doi.org/10.1056/NEJMoa2502081
Frequently asked questions
Q: What is the main difference between eloralintide and cagrilintide?
A: Eloralintide has been studied primarily as a standalone selective amylin receptor agonist, while cagrilintide has been studied predominantly in combination with semaglutide as CagriSema. Both engage amylin receptor pathways, but their clinical development programs test different questions — monotherapy efficacy versus combination efficacy.
Q: Which compound has shown greater weight loss in trials?
A: Cagrilintide, in the CagriSema combination, produced 20.4% mean weight loss at 68 weeks in the Phase 3 REDEFINE 1 trial. Eloralintide monotherapy produced up to 20% weight loss at 48 weeks in its Phase 2 trial at the highest dose arms. Because one figure reflects combination therapy and the other reflects monotherapy, researchers should not treat these as a direct apples-to-apples comparison.
Q: Is eloralintide FDA-approved?
A: No. Eloralintide remains investigational as of mid-2026, with an active Phase 3 program covering type 2 diabetes, obstructive sleep apnea, and combination and add-on regimens. No New Drug Application has been filed for eloralintide as of this writing.
Q: Is cagrilintide FDA-approved?
A: No, but it is further along the regulatory pathway. Novo Nordisk submitted a New Drug Application for CagriSema, the cagrilintide-semaglutide combination, in December 2025, with an FDA decision expected in late 2026.
Q: Can eloralintide and cagrilintide be used together with other GLP-1 or GIP compounds?
A: Both have been studied in combination contexts. Eloralintide's Phase 3 program includes a trial combining it with the GIP-agonist macupatide (NCT07215559) and an add-on trial layering it onto an existing weekly incretin (NCT07392190). Cagrilintide's primary development pathway is itself a combination with semaglutide (CagriSema), tested in REDEFINE 1.
See also:
- Cagrilintide vs Semaglutide: Amylin-GLP-1 Combination vs GLP-1 Monotherapy in Metabolic Research — compares cagrilintide's combination approach against GLP-1 monotherapy in more depth.
- VK2735 vs Retatrutide: Which Investigational Incretin Agonist Leads the Injectable Obesity Pipeline? — another head-to-head look at competing investigational obesity compounds.
- Best Peptides for Weight Loss Research: 9 Compounds Ranked — broader ranked overview of the weight-loss research landscape, including amylin-pathway compounds.
For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.