• Shweta Urva, Tamer Coskun, Corina Loghin, Xuewei Cui, Emily Beebe, Libbey O'Farrell, Daniel A Briere, Charles Benson, Michael A Nauck, and Axel Haupt.
• Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
• Diabetes Obes Metab. 2020 Oct 1; 22 (10): 1886-1891.

AbstractThe effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP-1RAs in non-clinical and clinical studies. GE was assessed following acute and chronic treatment with tirzepatide in diet-induced obese mice versus semaglutide or long-acting GIP analogue alone. Participants [with and without type 2 diabetes (T2DM)] from a phase 1, 4-week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. In mice, tirzepatide delayed GE to a similar degree to that achieved with semaglutide; however, these acute inhibitory effects were abolished after 2 weeks of treatment. GIP analogue alone had no effect on GE or on GLP-1's effect on GE. In participants with and without T2DM, once-weekly tirzepatide (≥5 and ≥4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy participants. In participants with T2DM treated with an escalation schedule of tirzepatide 5/5/10/10 or 5/5/10/15 mg, a residual GE delay was still observed after multiple doses. These data suggest that tirzepatide's activity on GE is comparable to that of selective GLP-1RAs.© 2020 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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