Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2026

Safety, tolerability, pharmacokinetics and pharmacodynamics of eloralintide and tirzepatide co-administered as once-weekly subcutaneous injections (144702)

Shobha Bhattachar 1 , Rebecca Taylor 1 , Kazumasa Takenouchi 1 , Risa Nasu 1 , Lai San Tham 1 , Surya Bhamidipaty-Pelosi 1 , Kenji Ohwaki 1 , Edward John Pratt 1 , Kieren J. Mather 1 , Samantha Hocking 2
  1. Eli Lilly and Company, Indianapolis, IN, USA
  2. Royal Prince Alfred Hospital, Sydney, Australia

Background: We assessed tirzepatide (TZP; long-acting GIP and GLP-1 receptor agonist) and eloralintide (elora; long-acting selective amylin receptor agonist) alone and in combination in two Phase-1b multiple-ascending-dose proof-of-concept studies (Study-A and Study-B).

Methods: In these investigator- and participant-blinded, placebo (PBO)-controlled studies, adults with obesity/overweight, without type 2 diabetes, with stable body weight, and BMI of 27−45kg/m2 (Study-A) or 27−40kg/m2 (Study-B) were enrolled. Participants received elora and/or TZP at various doses and combinations, vs PBO controls. Treatment duration varied by cohort depending on the dose regimen, ranging from 16-32 weeks. Endpoints included safety and percent change in body weight from baseline.

Results: In Studies-A and -B, 65% (62/96) and 25% (16/64) of participants were female, respectively; mean ages were 45 and 42 yrs, weights 94 and 87kg, and BMIs 32.8 and 30.5kg/m2 at baseline.  

The elora plus TZP arms had higher rates of all treatment-emergent adverse events (TEAEs) than PBO plus TZP or elora plus PBO.  The most common TEAEs were gastrointestinal events; most were mild to moderate in severity.

In Studies-A and B , the highest-dose combination arm (elora 9mg [initiated at 3mg] plus TZP 15mg [initiated at 2.5mg] dose-escalated every 4 weeks) resulted in maximum mean body weight reductions of 29.0% (Week-32, estimated treatment difference (90%CI) = -11.2(-14.7,-7.7)) and 25.5% (Week-24, estimated treatment difference (90%CI) = -25.0(-27.3,-22.7)).

Conclusion: Elora plus TZP resulted in weight reduction that exceeded the weight reduction with PBO plus TZP in all dose levels. The high dose combinations showed body weight loss of up to 29% (% change from baseline)at Week-32. Low dose combinations may produce weight reduction comparable to high dose TZP monotherapy, with fewer dose escalation steps. Both of these profiles may be of value in the approach to weight management. Phase 2 will better inform optimal dose combinations and dose-escalation schemes.