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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
Author(s) -
Urva Shweta,
Coskun Tamer,
Loghin Corina,
Cui Xuewei,
Beebe Emily,
O'Farrell Libbey,
Briere Daniel A.,
Benson Charles,
Nauck Michael A.,
Haupt Axel
Publication year - 2020
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14110
Subject(s) - semaglutide , dulaglutide , gastric emptying , exenatide , agonist , medicine , glucagon like peptide 1 , endocrinology , glucagon like peptide 1 receptor , placebo , receptor , type 2 diabetes , pharmacology , diabetes mellitus , liraglutide , stomach , alternative medicine , pathology
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.