Small intestinal glucose delivery affects the lowering of blood glucose by acute vildagliptin in type 2 diabetes

Abstract

Context: The rate of gastric emptying is an important determinant of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion, and may influence the magnitude of glucose-lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors. Objective: To evaluate the effects of the DPP-4 inhibitor, vildagliptin, during intraduodenal (ID) glucose infusion at two different rates within the physiological range of gastric emptying, in type 2 diabetes. Participants and Design: A total of 16 diet-controlled type 2 diabetic patients were studied on four separate days in double-blind, randomized, fashion. On each day, either 50mg vildagliptin or placebo was given 60min prior to a 120min ID glucose infusion at 2 or 4kcal/min (ID2 or ID4). Plasma glucose and hormones were measured frequently. Results: Plasma glucose, insulin, C-peptide, glucagon, total GIP, and total and intact GLP-1 concentrations were higher during ID4 than ID2 (P<0.01 for each). Compared with placebo, vildagliptin was associated with higher intact GLP-1, insulin and C-peptide, and lower glucose and total GIP and GLP-1 (P<0.01 for each), without affecting glucagon. There were significant interactions between the rate of ID glucose and vildagliptin treatment on plasma glucose, intact and total GLP-1, and GIP (P<0.05 for each), but not insulin, C-peptide or glucagon. The reduction in glucose and the increment in intact GLP-1 after vildagliptin vs. placebo were 3.3 and 3.8 fold greater respectively, during ID4 compared to ID2. Conclusions/Interpretation: These observations warrant further study to clarify whether type 2 diabetic patients with relatively more rapid gastric emptying have greater glucose-lowering during treatment with DPP-4 inhibitors.