OBJECTIVE—To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA_1c [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks.

RESULTS—Sitagliptin 100 and 200 mg produced significant (P < 0.001) placebo-subtracted reductions in A1C (−0.79 and −0.94%, respectively) and fasting plasma glucose (−1.0 mmol/l [−17.1 mg/dl] and −1.2 mmol/l [−21.3 mg/dl], respectively). Patients with baseline A1C ≥9% had greater reductions in placebo-subtracted A1C with sitagliptin 100 and 200 mg (−1.52 and −1.50%, respectively) than those with baseline A1C <8% (−0.57 and −0.65%) or ≥8 to <9.0% (−0.80 and −1.13%, respectively). In a meal tolerance test, sitagliptin 100 and 200 mg significantly decreased 2-h postprandial glucose (PPG) (placebo-subtracted PPG −2.6 mmol/l [−46.7 mg/dl] and −3.0 mmol/l [−54.1 mg/dl], respectively). Results for the above key efficacy parameters were not significantly different between sitagliptin doses. Homeostasis model assessment of β-cell function and proinsulin-to-insulin ratio improved with sitagliptin. The incidence of hypoglycemia was similar, and overall gastrointestinal adverse experiences were slightly higher with sitagliptin. No meaningful body weight changes from baseline were observed with sitagliptin 100 (−0.2 kg) or 200 mg (−0.1 kg). The body weight change with placebo (−1.1 kg) was significantly (P < 0.01) different from that observed with sitagliptin.

CONCLUSIONS—In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states, improved measures of β-cell function, and was well tolerated in patients with type 2 diabetes.