Eloralintide (LY3841136): Selective Amylin Agonist Phase 2 Data Explained

Eloralintide (development code LY3841136) is a selective long-acting amylin receptor agonist developed by Eli Lilly. Unlike Cagrilintide, which binds both amylin and calcitonin receptors, Eloralintide is engineered for amylin receptor selectivity, a design intended to reduce off-target signalling and improve tolerability ^[1].

Phase 2 Trial Outcomes

The 48-week, double-blind, placebo-controlled Phase 2 trial enrolled 263 adults with obesity, or overweight with at least one weight-related condition, and without type 2 diabetes. Weekly subcutaneous Eloralintide produced dose-dependent weight reduction of up to 20% at 48 weeks, versus 0.4% with placebo. Nausea and fatigue were the most common adverse events, and the investigators described Eloralintide as generally well tolerated ^[2].

Mechanism: Amylin Selectivity

Amylin is a 37-amino-acid hormone co-secreted with insulin by pancreatic beta cells. It slows gastric emptying, suppresses post-prandial glucagon, and acts centrally, principally through circumventricular brain regions that include the area postrema, to reduce food intake ^[3,4]. Selective amylin receptor agonism, distinct from dual amylin and calcitonin receptor agonism, is hypothesised to deliver appetite suppression with a cleaner downstream profile ^[1].

Eloralintide plus Tirzepatide

Eloralintide has also been studied alongside Tirzepatide. A Phase 1 study (NCT06916065) assessed the safety and pharmacokinetics of the two together, and in a 48-week Phase 2b trial in 367 adults with obesity or overweight and type 2 diabetes, the combination produced mean weight reductions of up to 23.3%, versus 14.8% with the highest Tirzepatide dose alone; gastrointestinal side effects were more frequent in the combination groups (Lilly, September 2026). The amylin plus dual incretin combination is one of several approaches being studied for next-generation obesity therapy, designed to engage complementary hormonal pathways that help regulate hunger and blood sugar.

Eloralintide vs Cagrilintide

• Receptor selectivity: Eloralintide targets amylin receptors selectively; Cagrilintide engages amylin and calcitonin receptors ^[1].
• Half-life: Both are engineered for once-weekly administration through fatty acid acylation ^[1].
• Combination data: Cagrilintide has the most mature combination dataset (CagriSema with Semaglutide, now in Phase 3) ^[5]; Eloralintide combination data with Tirzepatide is now emerging.

Research Procurement Considerations

Eloralintide is not commercially available as a research peptide at the time of writing. Laboratories interested in amylin pathway research currently work with Cagrilintide or Cagrilintide + Semaglutide blends as the closest available analogues. When Eloralintide reaches research-grade supply, verify HPLC purity at 99% or above, mass spectrometry confirmation of the acylated structure, and endotoxin below 0.5 EU/mg for cell-based work.

References

1. [1] Briere DA, et al. "Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept." Mol Metab. 2025;102:102271. PubMed 41109426
2. [2] Billings LK, et al. "Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial." Lancet. 2025;406(10520):2631-2643. PubMed 41207310
3. [3] Hay DL, et al. "Amylin: Pharmacology, Physiology, and Clinical Potential." Pharmacol Rev. 2015;67(3):564-600. PubMed 26071095
4. [4] Dehestani B, et al. "Amylin as a Future Obesity Treatment." J Obes Metab Syndr. 2021;30(4):320-325. PubMed 34929674
5. [5] Garvey WT, et al. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity." N Engl J Med. 2025;393(7):635-647. PubMed 40544433