Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes.
OBJECTIVE
To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes.


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 >or=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 >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 beta-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 beta-cell function, and was well tolerated in patients with type 2 diabetes.
Aschner
Pablo
P
Colombian Diabetes Association, Bogotá, Colombia.
Kipnes
Mark S
MS
Lunceford
Jared K
JK
Sanchez
Matilde
M
Mickel
Carolyn
C
Williams-Herman
Debora E
DE
D058892:Adenosine Deaminase Inhibitors; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D006442:Glycated Hemoglobin / Q000032:analysis; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
D058892:Adenosine Deaminase Inhibitors; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D010919:Placebos; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C042807:DPP4 protein, human