3082-LB

The selective amylin analog, eloralintide, enhanced weight-loss efficacy when combined with tirzepatide in diet-induced obese rats.

Authors: Daniel A. Briere1, Libbey O’Farrell1, Cassidy Howard1, Dawn Allen1, Cathy Clutinger1, Tamer Coskun1, Julie S. Moyers1, Amy L. Cox1

1 Eli Lilly and Company, Indianapolis, IN, USA
Sponsored by Eli Lilly and Company

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OBJECTIVE
  • To evaluate eloralintide (LY3841136), a long-acting selective amylin agonist, in combination with tirzepatide, a GIP and GLP-1 receptor agonist, for the treatment of obesity in diet-induced obese rats.
CONCLUSION
  • Combinations of eloralintide and tirzepatide, either as co-administration or adjunctive treatment, led to additive weight loss effects in DIO rats.
  • These observations support clinical investigation of eloralintide as an obesity therapeutic in combination with tirzepatide.
CO-ADMINISTRATION – BODY WEIGHT CHANGES
Simultaneous treatment of eloralintide and tirzepatide enhanced body weight loss in diet-induced obese rats.​
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ADJUNCTIVE – BODY WEIGHT CHANGES
Add-on treatment of eloralintide to tirzepatide dose-dependently enhanced body weight loss in diet-induced obese rats.
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CO ADMINISTRATION - DAILY FOOD INTAKE
Simultaneous treatment of eloralintide and tirzepatide enhanced daily food intake reductions in diet-induced obese rats.
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ADJUNCTIVE - DAILY FOOD INTAKE
Add-on treatment treatment of eloralintide and tirzepatide enhanced daily food intake reductions in diet-induced obese rats.​
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CO-ADMINISTRATION – % CHANGES AT 4 WEEKS
Simultaneous treatment of eloralintide and tirzepatide resulted in additive effects on changes in body weight and fat mass.
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ADJUNCTIVE – % CHANGES AT 4 WEEKS
Add-on treatment of eloralintide to ongoing tirzepatide resulted inadditive effects on changes on body weight and fat mass.​
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MATERIALS AND METHODS
  • Co-administration studies: Male Long Evans DIO rats were subcutaneously dosed every 3 days (Q3D) with vehicle, tirzepatide at 30 nmol/kg, eloralintide at 100 nmol/kg, or separate injections of tirzepatide and eloralintide for 4 weeks.
  • Adjunctive studies: DIO rats were dosed Q3D for 2 weeks with tirzepatide at 30 nmol/kg, followed by addition of 1, 10, or 100 nmol/kg Q3D of eloralintide to ongoing tirzepatide for 2 further weeks.
  • Body weights and food intake were measured daily. Fat mass measured at baseline and 4 weeks using QNMR.
RESULTS
  • Co-administration of tirzepatide at 30 nmol/kg and eloralintide at 100 nmol/kg for 4 weeks in DIO rats resulted in additive effects (-20%) on changes in body weight compared to eloralintide (-10%) or tirzepatide (-9%) alone.
  • For adjunctive treatment, two weeks of tirzepatide at 30 nmol/kg, followed by the addition of eloralintide at 100 nmol/kg for 2 additional weeks, resulted in additive body weight lowering (-21%) compared to eloralintide (-10%) or tirzepatide alone (-9%).
  • Lower adjunctive combinations of eloralintide (1 & 10 nmol/kg) led to enhanced weight loss (-11% or -15%) versus tirzepatide alone.
  • This enhanced weight loss was mediated, at least in part, by further and prolonged reductions in daily food intake and reflected in greater changes in fat mass at 4 weeks of treatment.

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Sponsor: Eli Lilly and Company.

Congress: American Diabetes Association — 86th Annual Scientific Sessions, New Orleans, LA, USA. 5–8 June 2026.

Poster ID: 3082-LB.

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