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

• Published in: Journal of diabetes investigation Vol. 12; no. 12; pp. 2162 - 2171
• Main Authors: Kuwata, Hitoshi, Yabe, Daisuke, Murotani, Kenta, Fujiwara, Yuuka, Haraguchi, Takuya, Kubota, Sodai, Kubota‐Okamoto, Saki, Usui, Ryota, Ishitobi, Minori, Yamazaki, Yuji, Hamamoto, Yoshiyuki, Kurose, Takeshi, Seino, Yusuke, Yamada, Yuichiro, Seino, Yutaka
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.12.2021; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Agonists; Apolipoprotein B-48 - metabolism; Blood Glucose - drug effects; Body weight; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetic neuropathy; Female; Gastric emptying; Gastric Emptying - drug effects; Gastric Inhibitory Polypeptide - metabolism; GLP-1 receptor agonists; GLP‐1 receptor agonist; Glucagon; Glucagon - drug effects; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptides - analogs & derivatives; Glucagon-Like Peptides - pharmacology; Glucose; Humans; Hypoglycemic Agents - pharmacology; Immunoglobulin Fc Fragments - pharmacology; Insulin; Insulin - blood; islet hormones; Japan; Laboratories; Liraglutide - pharmacology; Male; Middle Aged; Observational studies; Original; Peptides; Peptides - pharmacology; Postprandial Period - drug effects; Prospective Studies; Recombinant Fusion Proteins - pharmacology; Secretions; Japan; islet hormones; Gastric emptying; GLP-1 receptor agonist
• ISSN: 2040-1116; 2040-1124; 2040-1124
• DOI: 10.1111/jdi.13598

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. GLP‐1 receptor agonists (lixisenatide, liraglutide, and dulaglutide) were found to improve postprandial glucose excursions in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose‐lowering effects were observed.