Mechanism of Action
Selective AMY1R Activation
Amylin receptors are heterodimers of the calcitonin receptor (CTR) with receptor activity-modifying proteins (RAMP1, RAMP2, RAMP3), forming AMY1R, AMY2R, and AMY3R. In cell-based assays, eloralintide preferentially activates human AMY1R by roughly 12-fold over CTR and 11-fold over AMY3R, a selectivity profile distinct from non-selective amylin analogs like cagrilintide and pramlintide. AMY1R is expressed in the area postrema and hypothalamus, where its activation drives satiety and reduced food intake, while sparing CTR-mediated effects that are more associated with the GI side-effect burden of less-selective amylin agonists.
Fat Mass vs Lean Mass (Rat Data Only)
In rat studies, eloralintide's dose-dependent reduction in food intake and body weight occurred primarily through loss of fat mass. No body-composition (DEXA) data has been reported from human trials, so whether eloralintide preserves lean mass better than GLP-1 agonists in people remains an open question, not an established finding.
EloraTZP: Combination with Tirzepatide
Eloralintide has been studied in combination with tirzepatide (a dual GIP/GLP-1 receptor agonist), under the name EloraTZP, given as separate injections. Pairing an amylin-pathway agent with a GIP/GLP-1 dual agonist targets largely non-overlapping satiety circuits, which Lilly's Phase 2b data shows produces greater weight loss than tirzepatide alone, plus additional improvements in A1C.
Research Summary
Monotherapy (Phase 2, NCT06230523)
Phase 2 CompleteDouble-blind, placebo-controlled trial, 263 adults with obesity/overweight (no type 2 diabetes), 48 weeks, once-weekly subcutaneous. Mean body weight change vs placebo (-0.4%): 1 mg -9.5%, 3 mg -12.4%, 6 mg -17.6%, 9 mg -20.1%; escalation arms 6/9 mg -19.9% and 3/6/9 mg -16.4%. Published in The Lancet and presented at ObesityWeek 2025.
EloraTZP Combination (Phase 2b, NCT06603571)
Phase 2b CompleteDouble-blind, placebo-controlled trial, 367 adults with obesity/overweight AND type 2 diabetes (US and Argentina), 48 weeks, randomized to placebo, eloralintide alone, tirzepatide alone, or one of four EloraTZP dose pairs given as separate injections. Weight loss: 3 mg + tirzepatide 5 mg = 13.2%, 6 mg + 5 mg = 19.4%, 6 mg + 10 mg = 19.9%, 9 mg + 15 mg = 23.3% (highest dose, vs 14.8% for tirzepatide 15 mg alone). A1C reduction 2.2-2.9% across EloraTZP arms vs 2.4% for tirzepatide alone. Presented at EASD 2026.
Phase 3 Program (ENLIGHTEN)
Active ResearchLilly's Phase 3 ENLIGHTEN program is enrolling multiple trials: ENLIGHTEN-2 (NCT07282600, obesity/overweight with type 2 diabetes) and ENLIGHTEN-4 (NCT07353931, a master protocol studying obesity/overweight with knee osteoarthritis pain), plus additional studies including a tirzepatide-combination trial (NCT06916065), a Chinese-population trial (NCT06916091), and an obstructive sleep apnea trial (NCT07369011).
Research Protocols
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Phase 2 monotherapy reference | 1 mg, 3 mg, 6 mg, or 9 mg once weekly (fixed-dose arms) | Weekly | Subcutaneous |
| Phase 2 escalation reference | 3 mg -> 6 mg -> 9 mg, or 6 mg -> 9 mg | Weekly | Subcutaneous |
| EloraTZP Phase 2b reference | Eloralintide 3-9 mg + tirzepatide 5-15 mg, co-administered as separate weekly injections | Weekly | Subcutaneous |
Not yet approved. These are published Phase 2/2b trial arm designs (NCT06230523, NCT06603571), shown for research reference only, not a consumer protocol, vendor research-peptide recipe, or medical recommendation. No vendor has published a human-dosing vial size (not even the chemical-reagent suppliers that list eloralintide for lab research use), so the calculator below defaults to a placeholder vial, enter your own vial size and water volume.
Interactions
Safety Profile
The most common side effects reported in the monotherapy trial were mild-to-moderate gastrointestinal symptoms and fatigue, occurring more frequently at higher doses and reduced with slower dose escalation. No long-term human safety data exists yet; eloralintide remains in Phase 3 trials.
References
- [1]Eli Lilly and Company. Phase 2 monotherapy results (NCT06230523), published in The Lancet, presented at ObesityWeek 2025.
- [2]Eli Lilly and Company. EloraTZP Phase 2b combination results (NCT06603571), presented at EASD 2026.
- [3]ClinicalTrials.gov. ENLIGHTEN-2 (NCT07282600) and ENLIGHTEN-4 (NCT07353931) Phase 3 trial registrations.