Predicting steady-state HbA1c responses to sitagliptin in patients with type 2 diabetes mellitus.
OBJECTIVE
To develop predictive formulas using short-term changes in glycaemic parameters [haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG)] with sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, to assess longer term steady-state changes in HbA1c.


METHODS
Results from two, 12-week, double-blind studies of sitagliptin in Japanese patients with type 2 diabetes mellitus receiving once-daily sitagliptin 100 mg were used to construct linear models to develop predictive formulas based on study 1 (S1) and to validate them using study 2 (S2). HbA1c and FPG were the primary and the key secondary end-point for both studies and were both used to develop predictive formulas.


RESULTS
The predictive formulas using HbA1c+/-FPG results (slope of change) from week 0 to week 4 in S1 showed high correlations between fitted and observed week 12 HbA1c: for HbA1c alone R2=0.76, for HbA1c+FPG R2=0.89. When using the sitagliptin 100 mg group of S2 data set to assess the validity of the predictive formulas, high correlations for HbA1c alone (R2=0.76) and for HbA1c+FPG (R2=0.77) were also observed. Data using a lower dose (25 mg once daily) of sitagliptin also demonstrated similar results.


CONCLUSIONS
The early responses (over 4 weeks) in HbA1c and FPG with sitagliptin can be used to accurately predict later responses (at week 12) in HbA1c in Japanese patients with type 2 diabetes mellitus. Additional studies applying this approach to other agents with diverse mechanisms are important.
Kanazu
S
S
Banyu Pharmaceutical Co., Ltd., Tokyo, Japan. shinichi_kanazu@merck.com
Horie
Y
Y
Narukawa
M
M
Nonaka
K
K
Taniguchi
T
T
Arjona Ferreira
J C
JC
Takeuchi
M
M
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles