Abstract
INTRODUCTION: To investigate canagliflozin-induced changes in postprandial total glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: Forty-five patients with T2DM who had inadequate glycemic control (glycated hemoglobin ≥ 6.5%) with diet and exercise alone (n = 15, drug naïve) and in combination with either a stable dose of the α-glucosidase inhibitor acarbose (n = 15) or metformin (n = 15) received canagliflozin, a sodium-glucose cotransporter 2 inhibitor, at 100 mg once daily for 12 weeks. The primary endpoint was the change from baseline to week 12 in postprandial glucose and plasma levels of total GLP-1 and GIP during a meal tolerance test (MTT). RESULTS: Canagliflozin significantly reduced postprandial blood glucose (mean difference - 40.2 mg/mL at 60 min) and increased postprandial total GLP-1 (mean difference 1.8 pg/mL at 60 min) during an MTT. A transient reduction in the postprandial GIP level at only 30 min (mean difference - 80.3 pg/mL) during an MTT was observed. No changes in postprandial GLP-1 or GIP levels were seen after canagliflozin treatment as an add-on to acarbose in patients with T2DM. Acarbose treatment significantly decreased postprandial total GIP levels (P < 0.05) and tended to increase postprandial total GLP-1 levels (P = 0.07) compared to the other two treatments prior to canagliflozin. CONCLUSION: Canagliflozin 100 mg increased postprandial total GLP-1 levels in the absence of acarbose, suggesting that it may upregulate GLP-1 secretion through delayed glucose absorption in the upper intestine, as with the α-glucosidase inhibitor. TRIAL REGISTRATION: University Hospital Medical Information Network, UMIN000018345. FUNDING: Mitsubishi Tanabe Pharma Corporation.