Very Short-Term Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on the Secretion of Insulin, Glucagon, and Incretin Hormones in Japanese Patients with Type 2 Diabetes Mellitus: Analysis of Meal Tolerance Test Data

Background Sitagliptin inhibits dipeptidyl peptidase-4, which inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. To assess its antidiabetic potency, we used meal tolerance tests (MTTs) to determine the very short-term effects of sitagliptin on plasma concentrations of insulin and glucagon. Methods On day 1, patients with newly diagnosed or uncontrolled type 2 diabetes mellitus started a calorierestricted diet. On day 2, the first MTT was performed, before treatment with sitagliptin 50 mg/day started later the same day. On day 5, a second MTT was performed. Area under the concentration-time curves (AUCs) of relevant laboratory values were calculated [AUC from time zero to 2 h (AUC(0-2h)) and from time zero to 4 h (AUC(0-4h))]. Results Fifteen patients were enrolled. AUCs for postprandial plasma glucose were decreased after 3 days of sitagliptin treatment [AUC(0-2h) 457 +/- 115 mg/dL.h (25.4 +/- 6.4 mmol/L.h) to 369 +/- 108 mg/dL.h (20.5 +/- 6.0 mmol/L.h); AUC(0-4h) 896 +/- 248 mg/dL.h (49.7 +/- 13.8 mmol/L.h) to 701 +/- 246 mg/dL.h (38.9 +/- 13.7 mmol/L.h); both p<0.001]. AUC(0-2h) and AUC(0-4h) for postprandial plasma glucagon also decreased: 195 +/- 57 to 180 +/- 57 pg/mL.h (p<0.05) and 376 +/- 105 to 349 +/- 105 pg/mL.h p<0.01), respectively. The AUC(0-2h) [median with quartile values (25 %, 75 %)] for active GLP-1 increased: 10.5 (8.5, 15.2) to 26.4 (16.7, 32.4) pmol/L.h (p = 0.03). Conclusions Very short-term (3-day) treatment with sitagliptin decreases postprandial plasma glucose significantly. This early reduction in glucose may result partly from suppression of excessive glucagon secretion, through a direct effect on active GLP-1. Improvement in postprandial plasma glucose, through suppression of glucagon secretion, is believed to be an advantage of sitagliptin for the treatment of patients with type 2 diabetes.