The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists.
The 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.
['Urva|Shweta|S|0000-0002-3681-479X', 'Coskun|Tamer|T|', 'Loghin|Corina|C|', 'Cui|Xuewei|X|', 'Beebe|Emily|E|', "O'Farrell|Libbey|L|", 'Briere|Daniel A|DA|', 'Benson|Charles|C|', 'Nauck|Michael A|MA|0000-0002-5749-6954', 'Haupt|Axel|A|0000-0003-4502-0470']
D000818:Animals D001786:Blood Glucose D003924:Diabetes Mellitus, Type 2 D005746:Gastric Emptying D005749:Gastric Inhibitory Polypeptide D052216:Glucagon-Like Peptide 1 D000067757:Glucagon-Like Peptide-1 Receptor D005947:Glucose D051379:Mice
GIP type 2 diabetes GLP-1 analogue antidiabetic drug incretin therapy