The Novel Dual GIP and GLP‐1 Receptor Agonist, Tirzepatide, Transiently Delays Gastric Emptying Similarly to Selective Long‐Acting GLP‐1 Receptor Agonists

OBJECTIVE The effect of dual GIP and GLP-1 receptor agonist (RA), tirzepatide, on gastric emptying (GE) was compared to that of GLP-1RA in nonclinical and clinical studies. MATERIALS AND METHODS GE was assessed following acute and chronic treatment with tirzepatide in diet-induced obese mice versus semaglutide or long-acting GIP analogue alone. Subjects (with and without T2DM) from a Phase 1, 4-week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. RESULTS In mice, tirzepatide delayed GE to a similar degree as semaglutide; however, these acute inhibitory effects were abolished after 2-week treatment. GIP analogue alone had no effect on GE or on GLP-1's effect on GE. In subjects with and without T2DM, once weekly tirzepatide (≥5 mg and ≥ 4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy subjects. In patients with T2DM treated with an escalation schedule of 5/5/10/10 mg 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.