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

Ahrén B, Gomis R, Standl E, Mills D, Schweizer A. Diabetes Care. 2004;27:2874-2880.

Dipeptidyl peptidase IV (DPP-IV) is an enzyme involved in the degradation of the incretin hormone glucagon-like peptide 1 (GLP-1), which stimulates meal-response insulin secretion. The purpose of this randomized, double-blind, placebo-controlled study was to examine the efficacy of LAF237, a DDP-IV inhibitor, in combination with metformin in patients with type 2 diabetes. This is the first published study to report 1-year data of LAF237 and the efficacy of LAF237 as part of combination treatment.

Participants received LAF237 (50 mg once daily) or placebo in addition to ongoing treatment with metformin (1,500 to 3,000 mg/day). In the 12-week core study, 107 patients were randomized to treatment with LAF237 (n=56) or placebo (n=51). Of these patients, 71 were included in a 40-week extension study (LAF237, n=42; placebo, n=29). The patient population was predominantly male, white, and overweight, and approximately half were hypertensive. Mean age of patients was approximately 57 years.

At week 12, A1C decreased by 0.6±0.1% in patients treated with LAF237 (from 7.7±0.1% at baseline); there was no change in A1C from baseline in the placebo group. From week 12 to week 52, no change in A1C occurred in patients treated with LAF237, and A1C increased in the placebo group (baseline A1C: 7.9±0.1%). After 1 year, the between-group difference in A1C was 1.1±0.2% (P<.0001). At the end of the extension study (week 52), there were significant differences in patients receiving LAF237 versus placebo in mean prandial glucose (–2.4±0.6 mmol/L; P=.0001), insulin (40±16 pmol/L; P=.0153), and fasting plasma glucose (–1.1±0.5 mmol/L; P=.0312). LAF237 was generally well-tolerated, and the incidence of adverse events was similar for the 2 treatment groups.

In summary, LAF237 in combination with metformin was found to prevent the deterioration of glycemic control in patients with type 2 diabetes over a 1-year period. Further long-term studies involving a larger patient population that is more representative of the general diabetic population are needed.