Small Intestinal Glucose Delivery Affects the Lowering of Blood Glucose by Acute Vildagliptin in Type 2 Diabetes.
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.



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.



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.



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.



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.
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Tongzhi
T
Wu
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Xiang
X
Zhang
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Laurence G
LG
Trahair
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Michelle J
MJ
Bound
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Tanya J
TJ
Little
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Carolyn F
CF
Deacon
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Michael
M
Horowitz
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Karen L
KL
Jones
Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
Christopher K
CK
Rayner
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004386:Duodenum; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D000077597:Vildagliptin
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane