Eli Lilly announces that its experimental combination drug EloraTZP, which pairs the amylin-mimicking drug eloralintide with tirzepatide, achieved a record 23.3% average weight loss in a Phase 2 trial of patients with obesity and type 2 diabetes. While the efficacy outperforms Lilly's blockbuster Zepbound, high patient discontinuation rates of up to 27% due to gastrointestinal side effects raise tolerability concerns. Lilly plans to address this with optimized dosing schedules in Phase 3 trials slated to begin by the end of 2026.
Efficacy results of the Phase 2 trial
- ▪The EloraTZP combination treatment lowered average blood sugar levels, measured as A1C, by up to 2.9%, compared to a 2.4% reduction for tirzepatide alone and up to 1.4% for eloralintide alone
- ▪In Eli Lilly's 48-week Phase 2 trial of 367 adults with obesity and type 2 diabetes, highest-dose EloraTZP patients lost 23.3% (54 pounds), compared to 14.8% for tirzepatide alone, 12.3% for eloralintide alone, and 3% for placebo
Mechanism of the combination drug
- ▪EloraTZP combines eloralintide, an experimental selective amylin receptor agonist mimicking the pancreatic hormone amylin that signals fullness, with tirzepatide, the active ingredient in Eli Lilly's Zepbound and Mounjaro that targets GLP-1 and GIP gut hormones
- ▪Eli Lilly's EloraTZP combination approach targets three nutrient-stimulated hormone pathways—GLP-1, GIP, and amylin—to lightly engage multiple natural satiety systems rather than heavily targeting a single hormone system
Tolerability and side effects
- ▪In Eli Lilly's Phase 2 trial, patient discontinuation rates due to side effects ranged from 10.8% to 27% for EloraTZP, compared to 2.9% for tirzepatide alone, up to 10.8% for eloralintide alone, and 16.7% for placebo
- ▪The most common side effects of EloraTZP were mild-to-moderate gastrointestinal issues that occurred primarily when patients increased doses, which Eli Lilly attributed to patients ramping up doses of two drugs simultaneously
Plans for Phase 3 trials
- ▪Eli Lilly plans to advance a co-formulation of EloraTZP in Phase 3 trials, allowing patients to administer both tirzepatide and eloralintide in a single injection
- ▪Eli Lilly plans to initiate Phase 3 clinical trials for the EloraTZP combination treatment by the end of 2026, which will include adjusted dosing schedules to improve tolerability
Debatable claims
- ▪EloraTZP's high patient discontinuation rate undermines its record-breaking weight-loss efficacy
- ▪Combining multiple hormone-mimicking drugs is a superior approach to treating obesity than single-agent therapies
- ▪Clinicians should reserve EloraTZP for patients who fail to respond to standard GLP-1 therapies
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