Sitagliptin is a highly selective orally active dipeptidyl peptidase-4 inhibitor recently approved in the United States for the treatment of type 2 diabetes. Ten healthy subjects received single oral doses of 25, 50, 100, 200 and 400mg final market image tablets in five separate treatment periods in randomized fashion to assess dose proportionality. Blood (up to 72h post-dose) and urine (up to 24h post-dose) samples for sitagliptin pharmacokinetic analysis were collected at prespecified times following administration of sitagliptin. Dose-proportionality of AUC0-∞, Cmax and C24h was assessed using a power-law model. The results of this study indicate that plasma AUC0-∞ increased in a dose-proportional manner over the 25–400mg dose range. Over the same dose range, plasma Cmax increased in a greater than dose-proportional manner and C24h increased in a modestly less than dose proportional manner. No clinically meaningful differences in Tmax or apparent t1/2 were noted across the dose range. Differences in the percentage of the sitagliptin dose excreted unchanged in urine (72.5% pooled across doses) and renal clearance (344ml/min pooled across doses) were not statistically significant. Sitagliptin was generally well tolerated at all the doses evaluated.