Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes

OBJECTIVE - To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment. RESEARCH DESIGN AND METHODS - We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing, together with the investigator to extend treatment to I year. Placebo (n = 51) or LAF237 (50 mg once daily, n = 56) was added to ongoing metformin treatment (1,500-3,000 mg/day). HbA(1c) and fasting plasma glucose (FPG) were measured periodically, and standardized meat tests were performed at baseline, week 12, and week 52. RESULTS - in patients randomized to LAF237, baseline HbA(1c) averaged 7.7 +/- 0.1% and decreased at week 12 (Delta = - 0.6 +/- 0.1%), whereas HbA(1c) did not change from a baseline of 7.9 +/- 0.1 % in patients given placebo (between-group difference in DeltaHbA(1c) = -0.7 +/- 0.1%, P < 0.0001). Mean prandial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 2.2 +/- 0.4 mmol/l (P < 0.0001) and 1.2 +/- 0.4 mmol/l (P = 0.0057), respectively, but plasma insulin levels were not affected. At end point of the extension, the between-group differences in change in mean prandial glucose, insulin, and FPG were -2.4 +/- 0.6 mmol/l (P = 0.0001), 40 +/- 16 pmol/l (P = 0.0153), and - 1.1 +/- 0.5 mmol/l (P = 0.0312), respectively. HbA(1c) did not change from week 12 to week 52 in LAF237-treated patients (n = 42) but increased in participants given placebo (n = 29). The between-group difference in DeltaHbA(1c) after 1 year was -1.1 +/- 0.2% (P < 0.0001). CONCLUSIONS - Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes.