Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes.
OBJECTIVE
The purpose of this study was to evaluate the efficacy and safety of sitagliptin as an add-on to metformin therapy in patients with moderately severe (hemoglobin A(1c) >or= 8.0% and <or= 11.0%) type 2 diabetes mellitus (T2DM).


METHODS
This was a multinational, randomized, placebo-controlled, parallel-group, double-blind study conducted in 190 patients with T2DM. After >or= 6 weeks of stable metformin monotherapy (>or= 1500 mg/day), patients were randomized to either the addition of sitagliptin 100 mg once daily or placebo to ongoing metformin for 30 weeks.


METHODS
The primary efficacy endpoint was reduction in hemoglobin A(1c) (HbA(1c)) measured after 18 weeks of sitagliptin treatment. Key secondary endpoints included reduction in fasting plasma glucose (FPG) and 2-hour (2-h) postprandial plasma glucose (PPG) at 18 weeks, and HbA(1c) at 30 weeks. The proportion of patients meeting the goal of HbA(1c) < 7.0% was also analyzed.


RESULTS
Sitagliptin significantly reduced HbA(1c), FPG, and 2-h PPG, compared with placebo (all p < 0.001). The net improvement in HbA(1c) was - 1.0% at both 18 and 30 weeks, and a significantly greater proportion of patients treated with sitagliptin achieved HbA(1c) < 7.0% by the end of the study (22.1% vs. 3.3%, p < 0.001). Sitagliptin was well-tolerated. Compared with placebo, sitagliptin had a neutral effect on body weight and did not significantly increase the risk of hypoglycemia or gastrointestinal adverse events.


CONCLUSIONS
Addition of sitagliptin 100 mg once daily to ongoing metformin therapy was well-tolerated and resulted in significant glycemic improvement in patients with moderately severe T2DM who were treated for 30 weeks.
Raz
Itamar
I
Diabetes Unit, Department of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Chen
Yu
Y
Wu
Mei
M
Hussain
Shehla
S
Kaufman
Keith D
KD
Amatruda
John M
JM
Langdon
Ronald B
RB
Stein
Peter P
PP
Alba
Maria
M
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles