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Type: Journal article
Title: Effects of sitagliptin on glycemia, incretin hormones, and antropyloroduodenal motility in response to intraduodenal glucose infusion in healthy lean and obese humans and patients with type 2 diabetes treated with or without metformin
Author: Wu, T.
Ma, J.
Bound, M.
Checklin, H.
Deacon, C.
Jones, K.
Horowitz, M.
Rayner, C.
Citation: Diabetes, 2014; 63(8):2776-2787
Publisher: American Diabetes Association
Issue Date: 2014
ISSN: 0012-1797
Statement of
Tongzhi Wu, Jing Ma, Michelle J. Bound, Helen Checklin, Carolyn F. Deacon, Karen L. Jones, Michael Horowitz and Christopher K. Rayner
Abstract: The impact of variations in gastric emptying, which influence the magnitude of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) secretion, on glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors is unclear. We evaluated responses to intraduodenal glucose infusion (60 g over 120 min [i.e., 2 kcal/min], a rate that predominantly stimulates GIP but not GLP-1) after sitagliptin versus control in 12 healthy lean, 12 obese, and 12 type 2 diabetic subjects taking metformin 850 mg b.i.d. versus placebo. As expected, sitagliptin augmented plasma-intact GIP substantially and intact GLP-1 modestly. Sitagliptin attenuated glycemic excursions in healthy lean and obese but not type 2 diabetic subjects, without affecting glucagon or energy intake. In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin. These observations indicate that in type 2 diabetes, 1) the capacity of endogenous GIP to lower blood glucose is impaired; 2) the effect of DPP-4 inhibition on glycemia is likely to depend on adequate endogenous GLP-1 release, requiring gastric emptying >2 kcal/min; and 3) the action of metformin to lower blood glucose is not predominantly by way of the incretin axis.
Keywords: Humans
Diabetes Mellitus, Type 2
Gastric Inhibitory Polypeptide
Blood Glucose
Hypoglycemic Agents
Drug Therapy, Combination
Double-Blind Method
Energy Intake
Gastrointestinal Motility
Glucagon-Like Peptide 1
Sitagliptin Phosphate
Rights: © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
DOI: 10.2337/db13-1627
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