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Effects of sequential treatment with lixisenatide, insulin glargine, or their combination on meal‐related glycaemic excursions, insulin and glucagon secretion, and gastric emptying in patients with type 2 diabetes
Author(s) -
Meier Juris J.,
Menge Björn A.,
Schenker Nina,
Erdmann Silke,
KahleStephan Melanie,
Schliess Freimut,
Kapitza Christoph,
Nauck Michael A.
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.13935
Subject(s) - lixisenatide , gastric emptying , medicine , insulin glargine , endocrinology , postprandial , insulin , type 2 diabetes , glucagon , metformin , diabetes mellitus , glucagon like peptide 1 receptor , glucagon like peptide 1 , agonist , basal insulin , receptor , stomach
Aim To examine the glucose‐lowering mechanisms of the glucagon‐like peptide‐1 receptor agonist lixisenatide after two subsequent meals and in combination with basal insulin. Materials and Methods Twenty‐eight metformin‐treated patients with type 2 diabetes were randomly assigned to treatment sequences with either lixisenatide or insulin glargine alone for 4 weeks, and a combination of both treatments for 4 weeks. Metabolic examinations were performed before and after each treatment period following breakfast and a late lunch 8 hours later. Results Lixisenatide mainly reduced postprandial glycaemia, while insulin glargine mainly reduced fasting glucose after breakfast ( P < 0.05). This was partially preserved after a late lunch ( P < 0.05). After breakfast, lixisenatide reduced insulin secretion and glucagon levels significantly. These effects were lost after a late lunch. Insulin glargine did not significantly reduce glucagon or insulin secretion. Gastric emptying was slowed by lixisenatide, but not by insulin glargine after breakfast. After the late lunch, lixisenatide slightly accelerated gastric emptying. Conclusions Lixisenatide decelerates gastric emptying after breakfast, thereby reducing glycaemic excursions, insulin secretion and glucagon levels. The glycaemic reduction persists until after a late lunch, despite accelerated gastric emptying. The combination with insulin glargine enhances the glucose‐lowering effect because of complementary modes of action.