Ristic S et al. (2005) Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab 7: 692–698

The INCRETIN HORMONES glucagon-like peptide 1 and glucose-dependent insulinotropic peptide are degraded by the enzyme dipeptidyl peptidase 4 (DPP4); DPP4 inhibitors have been developed to prolong the activity of these hormones and assist in treating type 2 diabetes. Ristic et al. have tested the efficacy, safety and tolerability of vildagliptin, a long-acting DPP4 inhibitor, in this randomized, double-blind, parallel-group, dose-finding study.

After 4 weeks on placebo, 279 patients from 91 centers (US and Russia) were allocated to receive once-daily doses of 25 mg, 50 mg or 100 mg vildagliptin, or twice-daily doses of placebo or 25 mg vildagliptin. Efficacy was determined by reduction in glycosylated hemoglobin levels, a measure of long-term glycemia. Other variables measured included mean levels of 4 h-postprandial glucose and insulin, and β-cell function.

Although all groups, including placebo, showed a reduction in glycosylated hemoglobin levels over the 12 weeks, intention-to-treat analysis showed this was significant only in patients administered once-daily 50 mg or 100 mg vildagliptin. The once-daily 50 mg dose was also associated with a significant reduction in mean 4 h-postprandial glucose level, and the once-daily 100 mg dose with a significant increase in mean 4 h-postprandial insulin as well as an increase in β-cell function. All doses appeared to be safe and well-tolerated.

A once-daily 50 mg or 100 mg dose of vildagliptin for 12 weeks has shown benefit for individuals with type 2 diabetes; further studies are underway to determine whether longer-term treatment will maintain glycemic control.