Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes.
OBJECTIVE
Sitagliptin, an oral, potent, and selective dipeptidyl peptidase-4 (DPP-4) inhibitor was evaluated as once-daily monotherapy in a 12-week randomized, double-blind, placebo-controlled, parallel group, dose-ranging study. Additionally, the glycemic response to sitagliptin 100 mg daily was evaluated as a once-daily (100 mg once-daily) or twice-daily (50 mg twice-daily) dosing regimen.


METHODS
In a multinational, double-blind, randomized, placebo-controlled, parallel-group, dose-range finding study, 555 patients, 23-74 years of age, with HbA(1c) of 6.5-10.0% were randomized to one of five treatment groups: placebo, sitagliptin 25, 50 or 100 mg once-daily, or sitagliptin 50 mg twice-daily for 12 weeks. The efficacy analysis was based on the all-patients-treated population using an ANCOVA model.


RESULTS
Mean baseline HbA(1c) ranged from 7.6 to 7.8% across treatment groups, with 29% of all patients with values < or =7%. After 12 weeks, treatment with all doses of sitagliptin significantly (p < 0.05) reduced HbA(1c) by -0.39 to -0.56% and fasting plasma glucose by -11.0 to -17.2 mg/dL relative to placebo, with the greatest reduction observed in the 100-mg once-daily group. Mean daily glucose was significantly (p < 0.05) reduced by -14.0 to -22.6 mg/dL with all doses of sitagliptin relative to placebo. HOMA-beta was significantly (p < 0.05) increased by 11.3-15.2 with all sitagliptin doses relative to placebo. QUICKI and HOMA-IR were not significantly changed with sitagliptin treatment. There were no significant differences observed between the sitagliptin 100 mg once-daily and 50 mg twice-daily groups for any parameter. For sitagliptin, the incidence of adverse events of hypoglycemia was low, with one event in each of the 25- and 50-mg once-daily and 50-mg twice-daily treatment groups and two events in the 100 mg once-daily treatment group. There was no mean change in body weight with sitagliptin relative to placebo. Study duration may be a limitation because the extent of the glycemic response and the safety and tolerability may not have been fully elucidated in this 12-week study.


CONCLUSIONS
Sitagliptin monotherapy improved indices of glycemic control compared to placebo and was generally well-tolerated in patients with type 2 diabetes. The glycemic response to treatment with sitagliptin 100 mg/day was similar between the sitagliptin 100-mg once-daily and 50-mg twice-daily dose regimens.
Hanefeld
Markolf
M
GWT-Technical University, Dresden, Germany.
Herman
Gary A
GA
Wu
Mei
M
Mickel
Carolyn
C
Sanchez
Matilde
M
Stein
Peter P
PP
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010919:Placebos; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C517652:hemoglobin A1c protein, human