Tirzepatide delayed (GE) in participants with type 2 diabetes after multiple doses.
In diet-induced obese mice, tirzepatide delayed GE similarly to semaglutide, but this effect disappeared after 2 weeks.
GIP analogue alone did not influence GE or enhance GLP-1's impact on GE.
In healthy participants, the GE delay from a single dose of tirzepatide or dulaglutide lessened after multiple doses.
Participants with type 2 diabetes experienced a persistent GE delay with an escalation schedule of tirzepatide.
Simplified
The effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on (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.
Key numbers
50%
Decrease in Acetaminophen Concentration
Observed in healthy participants at tirzepatide doses ≥4.5 mg.
86
Participants in Study
Composed of 33 healthy participants and 53 with T2DM.
Full Text
We can’t show the full text here under this license.
S.U., T.C., L.O., E.B., D.B., X.C., A.H., C.B. and C.L. are employees and shareholders of Eli Lilly and Company. M.A.N. has been a member of advisory boards or consulted for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Fractyl, GlaxoSmithKline, Intarcia, Menarini/Berlin Chemie, Merck, Sharp & Dohme and NovoNordisk. His institution has received grant support from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Intarcia, Menarini/Berlin‐Chemie, Merck, Sharp & Dohme, Novartis Pharma and Novo Nordisk A/S. He has served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme and Novo Nordisk A/S.
