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Effects of the DPP-4 Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects with Impaired Glucose Tolerance

¹Dallas Diabetes and Endocrine Center, Dallas, Texas
²Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
³Creighton Diabetes Center, Omaha, Nebraska
⁴University Hospital, Lund, Sweden
⁵Panum Institute, University of Copenhagen, Denmark
⁶Novartis Pharma AG, Basel, Switzerland

michelle.baron{at}novartis.com

ABSTRACT

Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT).

Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin – placebo) in the adjusted mean changes from baseline to endpoint in the total and incremental () AUC_0-2h for these analytes were assessed by ANCOVA; glucose AUC_0-2h was the primary outcome variable.

Results: Relative to placebo, vildagliptin increased GLP-1 (AUC, +6.0±1.2 pmol/l•h, P<0.001) and GIP (AUC, +46.8±5.4 pmol/l•h, P<0.001) and decreased glucagon (AUC, –3.0 ± 1.0 pmol/l•h, P=0.003). Although postprandial insulin levels were unaffected (AUC, +20.8±35.7 pmol/l•h, P=0.561), prandial glucose excursions were reduced (AUC, –1.0±0.3 mmol/l•h, P<0.001), representing 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC_0-2h/glucose AUC_0-2h was significantly increased (+6.4 ± 2.0 pmol•min^-1•m^-2•mM^-1, P=0.002). Adverse event profiles were similar in the two treatment groups and no hypoglycemia was reported.

Conclusions: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.

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