Effects of glucagon‐like peptide‐1 receptor agonists on secretions of insulin and glucagon and gastric emptying in Japanese individuals with type 2 diabetes: A prospective, observational study

Abstract

Aims/Introduction: Differences in the glucose-lowering mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting. Materials and Methods: A single-arm, prospective, observational study was conducted to evaluate the effects of various GLP-1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate. Participants were subjected to meal tolerance tests before and 2 weeks and 12 weeks after GLP-1RA initiation. Effects on postprandial secretions of glucose-dependent insulinotropic polypeptide (GIP) and apolipoprotein B48 were also investigated. Results: Eighteen subjects with type 2 diabetes received one of three GLP-1RAs, i.e., lixisenatide, n = 7; liraglutide, n = 6; or dulaglutide, n = 5. While 12-week administration of all of the GLP-1RAs significantly reduced HbA1c, only lixisenatide and liraglutide, but not dulaglutide, significantly reduced body weight. Postprandial glucose elevation was improved by all of the GLP-1RAs. Postprandial insulin levels were suppressed by lixisenatide, while insulin levels were enhanced by liraglutide. Postprandial glucagon levels were suppressed by lixisenatide. The gastric emptying rate was significantly delayed by lixisenatide, while liraglutide and dulaglutide had limited effects on gastric emptying. GIP secretion was suppressed by lixisenatide and liraglutide. Apolipoprotein B48 secretion was suppressed by all of the GLP-1RAs. Conclusions: All of the GLP-1RAs were found to improve HbA1c in a 12-week prospective observational study in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose-lowering effects and body weight reduction were observed.

Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial

“…The acetaminophen likely empties with the liquid phase of the meal, and, in fact, 1‐hour acetaminophen levels were reduced with liraglutide, suggesting slower gastric emptying. In addition, the use of 13C‐acetate as a meal marker (which may elute from the solid phase and empty with the liquid phase) documented gastric emptying rate was significantly delayed by lixisenatide, whereas liraglutide and dulaglutide had limited effects on gastric emptying [39]. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has advised that, at least for one GLP‐1 agonist or analogue, there is a causal relationship between delayed gastric emptying and liraglutide (EMA/429077/2019) [40].…”

Free Versus Fixed-Ratio Combination of Basal Insulin and GLP-1 Receptor Agonists in Type 2 Diabetes Uncontrolled With GLP-1 Receptor Agonists: A Systematic Review and Indirect Treatment Comparison

“…It reported a superior reduction of FPG, HbA1c, and body weight by long-acting agents with a lower incidence of symptomatic hypoglycemia and gastrointestinal adverse reactions ( 25 ). On the contrary, delayed gastric emptying by GLP-1RA was more preserved with short-acting agents ( 26 , 27 ). The differential actions of lixisenatide and liraglutide might affect the outcomes of FRCs containing each GLP-1RA, which need to be clarified in future research.…”

Acute effects of linagliptin on intact and total glucagon‐like peptide‐1 and gastric inhibitory polypeptide levels in insulin‐dependent type 2 diabetes patients with and without moderate renal impairment

“…Major exclusion criteria included diagnosis of type 1 diabetes mellitus, history of pancreatitis, and uncontrolled hypertension, defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >95 mmHg. Because of possible interference with GLP-1 and GIP levels, [15][16][17] patients treated with metformin, DPP-4 inhibitors, or GLP-1 analogues within 6 weeks prior to the study were also excluded. Insulin was allowed in order to reduce the risk of hyperglycaemia.…”