Small intestinal glucose delivery affects the glucose-lowering effect of acute vildagliptin in type 2 diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

T Wu, X Zhang, LG Trahair, MJ Bound, TL Little, Carolyn F. Deacon, M Horowitz, KL Jones, CK Rayner

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 (VILD), during intraduodenal (ID) glucose infusion at 2 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 4 separate days in double-blind, randomized, fashion. On each day, either 5-mg VILD or placebo (PLBO) was given 60 minutes before a 120-minute ID glucose infusion at 2 or 4 kcal/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 .01 for each). Compared with PLBO, VILD was
associated with higher intact GLP-1, insulin, and C-peptide and lower glucose and total GIP and GLP-1 (P .01 for each), without affecting glucagon. There were significant interactions between the rate of ID glucose and VILD treatment on plasma glucose, intact and total GLP-1, and GIP (P.05 for each) but not insulin, C-peptide, or glucagon. The reduction in glucose and the increment in intact
GLP-1 after VILD vs PLBO were 3.3- and 3.8-fold greater, respectively, during ID4 compared with 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.
Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number12
Pages (from-to)4769-4778
ISSN0021-972X
DOIs
Publication statusPublished - 2016

ID: 169969275