Hormonal and metabolic effects of morning or evening dosing of the dipeptidyl peptidase IV inhibitor vildagliptin in patients with type 2 diabetes

AIM

This randomized, double-blind, crossover study compared post-prandial hormonal and metabolic effects of vildagliptin, (an oral, potent, selective inhibitor of dipeptidyl peptidase IV DPP-4]) administered morning or evening in patients with type 2 diabetes.

METHODS

Forty-eight patients were randomized to once daily vildagliptin 100 mg administered before breakfast or before dinner for 28 days then crossed over to the other dosing regimen. Blood was sampled frequently after each dose at baseline (day ?1) and on days 28 and 56 to assess pharmacodynamic parameters.

RESULTS

Vildagliptin inhibited DPP-4 activity (>80% for 15.5 h post-dose), and increased active glucagon-like peptide-1 compared with placebo. Both regimens reduced total glucose exposure compared with placebo (area under the 0–24 h effect–time curve AUE(0,24 h)]: morning ?467 mg dl^?1 h, P = 0.014; evening ?574 mg dl^?1 h, P = 0.003) with no difference between regimens (P = 0.430). Reductions in daytime glucose exposure (AUE(0,10.5 h)) were similar between regimens. Reduction in night-time exposure (AUE(10.5,24 h) was greater with evening than morning dosing (?336 vs. ?218 mg dl^?1 h, P = 0.192). Only evening dosing significantly reduced fasting plasma glucose (?13 mg dl^?1, P = 0.032) compared with placebo. Insulin exposure was greater with evening dosing (evening 407 µU ml^?1 h; morning 354 µU ml^?1 h, P = 0.050).

CONCLUSIONS

Both morning and evening dosing of once daily vildagliptin 100 mg significantly reduced post-prandial glucose in patients with type 2 diabetes; only evening dosing significantly decreased fasting plasma glucose. Although evening dosing with vildagliptin 100 mg tended to decrease night-time glucose exposure more than morning dosing, both regimens were equally effective in reducing 24 h mean glucose exposure (AUE(0,24 h)) in patients with type 2 diabetes.