Educational reference only. Informational material drawn from peer-reviewed literature. Not medical advice and not a recommendation to use, dose, or modify any therapy. Decisions about hormone therapy should be made with a qualified healthcare provider.
Overview
Overview
Eloralintide (LY3841136) is Eli Lilly's investigational, long-acting, selective amylin receptor agonist for obesity, given as a once-weekly subcutaneous injection. It belongs to the fast-growing amylin-based class of weight-loss drugs, alongside cagrilintide (a non-selective amylin/calcitonin agonist, used in Novo Nordisk's CagriSema), amycretin (a combined GLP-1/amylin agonist), and others including petrelintide.
What sets it apart is selectivity. It was designed to activate amylin receptors while largely sparing the calcitonin receptor. The hypothesis is that this preserves weight loss while improving GI tolerability. In phase 2 it produced weight loss in the range of incretin drugs, and nausea was lower with gradual escalation.
Development status: a phase 1 multiple-ascending-dose trial and a 48-week phase 2 RCT (263 adults, The Lancet 2025) are published. Phase 3 (the ENLIGHTEN program) began enrolling in late 2025 and has no results yet. Eloralintide is not approved anywhere. This entry is pre-phase-3 and will be updated when ENLIGHTEN reads out.
Forms
Available forms & half-lives
| Form | Approximate half-life |
|---|---|
| Subcutaneous injection, once weekly (investigational; the only route studied) | ~14–16 days (mean 13.9–15.8 days) |
What it does
Main effects
- Reduced food intake and body weight: phase 2 mean weight loss ranged from about 9.5% (lowest dose arm) to 20.1% (highest dose arm) versus 0.4% on placebo at 48 weeks PMID: 41207310
- Increased fullness: amylin agonism at the brainstem (area postrema, nucleus of the solitary tract) and hypothalamus
- Slowed gastric emptying and suppressed post-meal glucagon (amylin physiology)
- Cardiometabolic improvements in phase 2: waist circumference, blood pressure, lipids, glycemic measures, and inflammation markers
- Fat-predominant weight loss in obese rats (preclinical; human body-composition data are pending)
- AMY1R selectivity (about 12-fold over the calcitonin receptor): the design hypothesis is preserved weight loss with better GI tolerability than non-selective amylin agonists; still being established in humans
- Distinct from GLP-1 drugs: no action at GLP-1 or GIP receptors; being developed both standalone and, potentially, as a partner to incretin drugs
What to watch for
Common side effects
- Nausea: 11–64% across phase 2 dose arms versus 14% on placebo; dose-related, highest when starting directly at higher exposure, lower with gradual escalation
- Fatigue: up to 46% across arms versus 12% on placebo; notably dose-related and more prominent than typically seen with GLP-1 drugs
- Decreased appetite (an expected pharmacologic effect), headache, diarrhea, vomiting, and constipation, mostly mild to moderate
- Injection-site reactions
- Discontinuation for adverse events rose with dose; about 7% in one escalation arm
- Class and theoretical: hypoglycemia with insulin or sulfonylureas, delayed gastric emptying (oral drug absorption, aspiration under anesthesia), gallbladder disease with rapid weight loss, dehydration, immunogenicity
- Long half-life: side effects can persist for weeks after the last injection
- Not available legitimately: research-grade "eloralintide" is unverified for identity, purity, sterility and potency
Key facts
Key facts worth knowing
- Eloralintide is a selective amylin receptor agonist: in human cell assays it preferentially activates AMY1R, about 12-fold over the calcitonin receptor (CTR) and about 11-fold over AMY3R. Non-selective agonists like cagrilintide activate CTR more strongly. PMID: 41109426
- A C20 fatty diacid attached to the amylin analog provides albumin binding and a half-life of about 14–16 days (mean 13.9–15.8 days), supporting once-weekly injection. Exposure rose proportionally with dose in phase 1. Phase 1 ADA 2025 abstract 882-P (half-life 13.9–15.8 days, dose proportionality)PMID: 41559929
- Phase 2 (48 weeks, 263 adults, The Lancet 2025): all arms beat placebo. Mean weight loss ranged from about 9.5% (lowest dose arm) to 20.1% (highest dose arm) versus 0.4% on placebo (efficacy estimand); the escalation arms reached about 16–20%. PMID: 41207310
- In rats, eloralintide cut food intake as much as cagrilintide but caused less conditioned taste avoidance, a proxy for nausea and aversion. Whether the selectivity advantage fully translates to humans is still being established; cross-trial comparisons with semaglutide are indirect. PMID: 41109426ADA 2025 preclinical abstract 849-P (C20 fatty diacid, comparison with cagrilintide)
- Fatigue (up to 46% across arms versus 12% on placebo) was notably dose-related and is more prominent than typically seen with GLP-1 drugs. It is the adverse event most worth tracking. PMID: 41207310
- Phase 3 (ENLIGHTEN) began enrolling in December 2025 (ENLIGHTEN-1, NCT07321886). No phase 3 results are available as of this entry, and eloralintide is not approved anywhere. This entry will be updated when ENLIGHTEN reads out. Lilly press release: phase 2 results and phase 3 startTrial tracker (ENLIGHTEN-1 registration)
Legal status
Legal status
Not approved anywhere. Investigational; available only in clinical trials. Not a controlled substance. Research-grade material sold as "eloralintide" is unverified for identity, purity, sterility and potency, and the fatty-acid modification makes authentic synthesis nontrivial.