Twelve-Week Efficacy and Tolerability of Sitagliptin, a Dipeptidyl Peptidase IV (DPP-IV) Inhibitor, in the Treatment of Type 2 Diabetes
Russell Scott*, Gary Herman, Jacqueline Yee, Jayne De La Cruz, Ling Wu, Xun Chen, Mei Wu, Peter Stein
Affiliation : * Christchruch Hospital, Christchurch, New Zealand, Merck Research Laboratories, Rahway, NJ, USA
Background and Aims. Sitagliptin (MK-0431) is an oral, potent, and selective DPP-IV inhibitor currently
under development for the treatment of type 2 diabetes.
Materials and Methods. In a randomized, double-blind, placebo-controlled, active-comparator, parallel
group, dose-range finding study, sitagliptin was evaluated in patients with type 2 diabetes. After an initial
diet/exercise phase and, for those on an antihyperglycemic agent, a drug wash off period, 743 patients aged
21-76 yrs who had A1C levels of 6.3 to 11.0% were randomized to one of 6 treatments: placebo; sitagliptin 5,
12.5, 25, or 50 mg b.i.d.; or glipizide 5 mg (up-titrated to 10, 15, and then to 20 mg/day) for a 12-wk treatment
period.
Results. Mean baseline A1C levels ranged from 7.8-7.9% across treatment groups, with 20.8% of patients
<7%. The efficacy analysis was based on a modified intention-to-treat population using an ANCOVA. At Week
12, treatment with all sitagliptin doses significantly reduced A1C compared to baseline with the largest
reductions in the 50 mg b.i.d. group: the placebo-subtracted differences in A1C ranged from -0.4 to -0.8% in
a dose-dependent manner for the sitagliptin treatment groups, and -1.0% with glipizide. At Week 12, placebo-
subtracted A1C results did not appear to have reached a plateau in the active treatment groups. FPG
increased by 0.44 mmol/L in the placebo group, and dose-dependently decreased by 0.04 to 1.01 mmol/L in the
sitagliptin groups, and by 1.38 mmol/L in the glipizide group. A similar reduction was also observed for other
glycemic endpoints including fructosamine and mean daily glucose. Treatment with sitagliptin was well
tolerated and resulted in no significant weight change, whereas a 1.1 kg weight gain was observed in the
glipizide group. Twenty-one patients (17.1%) in the glipizide group experienced one or more hypoglycemic
events compared to 3 (2.4%) patients in the placebo group and 0, 5 (4.1%), 5 (4.1%), and 2 (1.6%) patients
in the sitagliptin 5, 12.5, 25, 50 mg b.i.d. groups, respectively.
Conclusion. In this study, sitagliptin monotherapy was efficacious and generally well-tolerated in the treat-
ment of patients with type 2 diabetes. The study is continuing with an active-controlled treatment phase to
address the comparative efficacy, durability, ‚-cell function, and safety with longer term treatment.
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