Concurrent Use of Teneligliptin and Canagliflozin Improves Glycemic Control with Beneficial Effects on Plasma Glucagon and Glucagon-Like Peptide-1: A Single-Arm Study

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. 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 des-acyl 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 amount of postprandial insulin secretion. The underlying mechanisms may involve canagliflozin's inhibitory activity against not only SGLT2 but also SGLT1. Funding Mitsubishi Tanabe Pharma Corporation and a Grant for Clinical Research from Miyazaki University Hospital.