The Dipeptidyl Peptidase-4 Inhibitor Vildagliptin Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Fasting Glucose

Abstract

OBJECTIVE—To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and β-cell function in subjects with impaired fasting glucose (IFG).

RESEARCH DESIGN AND METHODS—A total of 22 subjects with IFG (11 female and 11 male, mean ± SD age 59.6 ± 11.5 years) were treated orally with 100 mg vildagliptin once daily in a single-blind study. Subjects received placebo for 2 weeks (run-in) followed by vildagliptin for 6 weeks (treatment) and then placebo for 2 weeks (washout). A frequently sampled intravenous glucose tolerance test (FSIGT), followed by a 2-h meal tolerance test (MTT), was performed at 2, 8, and 10 weeks. From the FSIGT, the acute insulin response to glucose (AIR_g) and insulin sensitivity index (S_I) were determined and used to compute the disposition index (AIR_g × S_I) as a measure of β-cell function.

RESULTS—Fasting plasma glucose did not change after 6 weeks of vildagliptin treatment. With treatment, mean ± SEM AIR_g increased from 224 ± 44 to 286 ± 52 pmol/l (P < 0.05), and S_I improved from 2.8 ± 0.5 to 3.5 ± 0.5 × 10⁻⁵ · min⁻¹ · pmol⁻¹ · l (P < 0.01), resulting in an increase in the disposition index from 688 ± 180 to 1,164 ± 318 × 10⁻⁵/min (P < 0.05). These effects were not sustained after washout. During the MTT, the incremental area under the glucose curve was significantly decreased after treatment (240 ± 15 vs. 191 ± 14 mmol · l⁻¹ · min⁻¹; P = 0.002), but this effect was not sustained after washout.

CONCLUSIONS—The DPP-4 inhibitor vildagliptin improves insulin sensitivity and β-cell function, leading to improved postprandial glycemia in subjects with IFG, who are known to have β-cell dysfunction. Thus, vildagliptin may prevent progression to diabetes in high-risk subjects.