Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes

Abstract

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 1 year. Placebo (n = 51) or LAF237 (50 mg once daily, n = 56) was added to ongoing metformin treatment (1,500–3,000 mg/day). HbA1c and fasting plasma glucose (FPG) were measured periodically, and standardized meal tests were performed at baseline, week 12, and week 52. RESULTS—In patients randomized to LAF237, baseline HbA1c averaged 7.7 ± 0.1% and decreased at week 12 (Δ = −0.6 ± 0.1%), whereas HbA1c did not change from a baseline of 7.9 ± 0.1% in patients given placebo (between-group difference in ΔHbA1c = −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. HbA1c 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 ΔHbA1c 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.