Concurrent Use of Teneligliptin and Canagliflozin Improves Glycemic Control with Beneficial Effects on Plasma Glucagon a
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ORIGINAL RESEARCH
Concurrent Use of Teneligliptin and Canagliflozin Improves Glycemic Control with Beneficial Effects on Plasma Glucagon and Glucagon-Like Peptide-1: A Single-Arm Study Tomoho Noda . Emi Ebihara . Hiroaki Ueno
. Keisuke Sadohara .
Yuri Tanaka . Yuuma Nagatomo . Yousuke Murakami . Shinichi Yonamine . Wakaba Tsuchimochi . Hideyuki Sakoda . Hideki Yamaguchi . Masamitsu Nakazato Received: May 21, 2019 Ó The Author(s) 2019
ABSTRACT Introduction: We investigated the mechanisms of the glucose-lowering effects of teneligliptin and canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, by monitoring several gastrointestinal peptides using the most appropriate measuring methods during multiple meal tolerance tests (MTTs) and flash glucose monitoring.
Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.8483387. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13300019-0666-7) contains supplementary material, which is available to authorized users. Tomoho Noda and Emi Ebihara are equally contributed first author. T. Noda E. Ebihara H. Ueno (&) K. Sadohara Y. Tanaka Y. Nagatomo Y. Murakami S. Yonamine W. Tsuchimochi H. Sakoda H. Yamaguchi M. Nakazato (&) Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan e-mail: [email protected] M. Nakazato e-mail: [email protected]
Methods: Twelve Japanese patients with type 2 diabetes were enrolled in the 14-day study. Subjects were treated with teneligliptin 20 mg/day from day 4, followed by a combination tablet of teneligliptin 20 mg and canagliflozin 100 mg (T/C) per day from day 11. MTTs were conducted on days 3 (premedication; Pre), 10 (teneligliptin; T) and 13 (T/C) to evaluate plasma glucose, C-peptide, glucagon, active glucagon-like peptide-1 (GLP-1), active gastric inhibitory polypeptide (GIP), ghrelin and desacyl ghrelin. Results: Plasma glucose was significantly decreased with the progress of treatment intervention, and C-peptide was significantly decreased in T/C compared to the others. Plasma postprandial glucagon was increased for 90 min from fasting in Pre, but only for 30 min in T and T/C. Plasma postprandial active GLP-1 was significantly increased in T compared to Pre, and that of T/C was significantly higher than T. Plasma postprandial active GIP was increased in T and T/C compared to Pre. Plasma ghrelin and des-acyl ghrelin levels did not change during the treatment. Conclusion: Teneligliptin increased incretin hormones and suppressed postprandial glucagon secretion as expected. Concurrent use of canagliflozin and teneligliptin improved glycemic control without increasing postprandial glucagon secretion, and increased postprandial GLP-1 secretion and decreased the required
Diabetes Ther
amount of postprandial insulin secretion. The underlying mechanisms may involve
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