Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year

To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related -cell function and insulin sensitivity over 52 weeks in type 2 diabetes. RESEARCH DESIGN AND METHODS -- In a 12-week core study, placebo (n 51) or vildagliptin (n 56; 50 mg OD) was added to metformin treatment (1.5-3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at 0, 12, 24, and 52 weeks; glucose, insulin, and C-peptide were evaluated. RESULTS -- In subjects completing 52 weeks with participation in all meal tests (n 57), HbA1c (A1C) decreased in the vildagliptin/metformin group (VM group, n 31) but increased in the placebo/metformin group (PM group, n 26; between-group difference 1.0 0.2%; P 0.001; baseline of all subjects combined 7.7 0.1%). Also, fasting glucose decreased in the VM group but increased in the PM group (difference 0.9 0.3 mmol/l, P 0.016; baseline 9.8 0.3 mmol/l). Insulin secretion (postmeal suprabasal area under the 0- to 30-min C-peptide curve divided by the 30-min increase in glucose) was increased in the VM group but was reduced in the PM group (difference 0.011 0.03 pmol/l 30 min/mmol/l, P 0.018; baseline 0.036 0.02). Insulin sensitivity during meal ingestion (oral glucose insulin sensitivity) increased in the VM group but was not altered in the PM group (difference 27 4 ml min 1 m 2 , P 0.036; baseline 246 6). Insulin secretion related to insulin sensitivity (adaptation index) increased in the VM group but decreased in the PM group (difference 3.2 1.0, P 0.040; baseline 9.1 0.5). The change in adaptation index correlated to the change in A1C (r 0.39, P 0.004). CONCLUSIONS -- This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves -cell function along with improved postmeal insulin sensitivity