What question did this study set out to answer?

This study aims to assess the weight-loss effects of the amylin analog eloralintide when administered with tirzepatide in diet-induced obese rats.

June 7, 2026

3082-LB: The Selective Amylin Analog Eloralintide Enhanced Weight-Loss Efficacy when Combined with Tirzepatide in DIO Rats

Key Points

This study aims to assess the weight-loss effects of the amylin analog eloralintide when administered with tirzepatide in diet-induced obese rats.
DIO rats were administered eloralintide, tirzepatide, or both for two weeks.
Food intake and body weight were measured daily during the treatment period.
Body composition was assessed at baseline and after treatment using QNMR.
Both eloralintide and tirzepatide significantly reduced food intake and body weight.
The combination therapy led to increased reductions in food intake and body weight compared to each agent alone.
Fat mass loss was also greater with the combination treatment than with individual therapies.

Abstract

Introduction and Objective: Eloralintide (LY3841136) is a long-acting and selective amylin analog in clinical development for the treatment of obesity. Given the complementary mechanisms of action exhibited by amylin and incretins, this study sought to evaluate the effects of combined therapy—both co-administration and adjunctive use—of eloralintide with tirzepatide, a GIP and GLP-1 receptor agonist, on food intake, body weight, and body composition in diet-induced obese (DIO) rats. Methods: For co-administration studies, male Long Evans DIO rats were subcutaneously dosed every 3 days with either vehicle, tirzepatide, eloralintide, or a combination of tirzepatide and eloralintide for 2 weeks. For adjunctive studies, DIO rats were dosed for 2 weeks with tirzepatide, followed by the addition of eloralintide to ongoing tirzepatide for an additional 2 weeks. Body weights and food intake were measured daily, and body composition was measured at baseline and the end of the study using QNMR. Results: In DIO rats, treatment with either eloralintide or tirzepatide significantly reduced food intake and lowered body weights. The combination of eloralintide and tirzepatide, as a co-administration and as adjunctive treatment, further enhanced food intake reductions, body weight lowering, and fat mass loss greater than treatment with either agent alone. Conclusion: The combination of eloralintide plus tirzepatide in DIO rats produced augmented weight loss greater than the effects of individual therapies. These observations support clinical investigation of eloralintide as an obesity therapeutic in combination with tirzepatide. Disclosure D.A. Briere: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. L. O'Farrell: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. C. Howard: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. D.M. Allen: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. C. Clutinger: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. T. Coskun: Employee; Current; Eli Lilly and Company. J.S. Moyers: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. A.L. Cox: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company.

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