Background: It has been suggested that short- and long-acting glucagon-like peptide 1 receptor agonists (GLP-1RAs) exert different actions on gastric emptying rate (GE). However, the alterations in gastric emptying and their contributions to postprandial glucose and lipid excursions have not been fully evaluated.
Methods: A 3-arm non-randomized trial was conducted in Japanese patients with type 2 diabetes. Meal tolerance test was performed before and 12 weeks after initiation of treatment by short-acting GLP-1RA (Lixisenatide (X)) or long-acting GLP-1RA [Liraglutide (R) or Dulaglutide(D)]. Plasma glucose, ApoB48, insulin and gastric emptying (13C breath test) were measured after taking a solid test meal. Data were presented as average±SD and evaluated using student’s or paired t-test. p<0.05 was considered significant.
Results: 18 patients were enrolled [X: n=7; age(year) 45.6±2.3; duration(year) 4.6±5.0; ΔCPR(glucagon stimulation test (mg/dl) 3.2±1.4, R: n=6; age 49.0±11.4; duration 8.2±9.2; ΔCPR 3.1±0.5, D; n=5; age 51.8±7.6; duration 4.6±3.8; ΔCPR 2.7±1.3)]. After 12 weeks administration, HbA1c was significantly improved in all groups [HbA1c (%), X: 8.2±1.6 to 6.3±0.4, L: 9.0±0.8 to 6.6±1.1, D: 8.6±0.9 to 6.6±0.3]. GE was delayed only in X [T1/2(min), X: 26.4±6.5 to 64.4±34.4, L: 33.5±15.5 to 29.1±9.2, and D: 26.3±3.8 to 31.1±9.7]. Postprandial insulin and ApoB48 secretion was significantly decreased only in X [IRI-AUC0-240(uIU/dlxmin), X: 11724.0±5582.0 to 6248.2±3718.7, L: 8206.7±3075.4 to 9905.0±3450.3, D: 9832.8±5087.3 to 10640.6±4195.1 and ApoB48-iAUC0-240(ug/mlxmin), X: 513.2±394.4 to -83.7±242.6; L: 745.1±352.4 to 534.1±193.4; and D: 983.5±239.0 to 568.2±374.4].
Conclusion: These results indicate that short-acting agents improve postprandial glycemic and lipidemic metabolism through delaying GE; long-acting agents improve glycemic control through enhanced insulin secretion.
H. Kuwata: Research Support; Self; Eli Lilly and Company. D. Yabe: Advisory Panel; Self; Abbott. Research Support; Self; Astellas Pharma Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Hamamoto: Speaker's Bureau; Self; Novo Nordisk A/S. T. Kurose: Consultant; Self; Taisho Pharmaceutical Co., Ltd. Speaker's Bureau; Self; FujiFilm Pharma, Ono Pharmaceutical Co., Ltd. Y. Seino: Research Support; Self; Arkray, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation.