Effects of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor, on blood glucose and plasma incretin and insulin responses to small intestinal glucose infusion, in healthy lean and obese subjects, and alone or in combination with metformin in patients with type 2 diabetes mellitus.

Healthy lean and obese subjects will each undergo two studies (sitagliptin 100 mg oral versus control), in double-blind, randomised fashion, separated by 3 - 14 days. Patients with type 2 diabetes will be studied on 4 occasions each: twice during therapy with metformin 850 mg twice daily for 7 days (days 5 and 8, sitagliptin 100 mg oral or control), and twice during treatment with a matching placebo twice daily for 7 days, with a washout period of 14 days between treatment periods. In the diabetic patients, the order of both metformin and placebo, and sitagliptin and control, will be randomised, except that during the second metformin/placebo treatment period, the order of sitagliptin and control will be identical to the first treatment period. On each study day, glucose will be infused into the duodenum at 2 kcal/min from 0 to 120 min. Within each group (healthy lean, healthy obese, diabetic), each subjects acts as his own control, but comparison will also be made between groups.