Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study.
OBJECTIVE
To evaluate the 2-year safety and efficacy of adding sitagliptin or glipizide to ongoing metformin in patients with type 2 diabetes.


METHODS
Patients who were on a stable dose of metformin (> or = 1500 mg/day) for at least 8 weeks were randomised in a double-blind manner to receive either sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (up-titrated up to 20 mg/day based upon prespecified glycaemic criteria) (N = 584). The efficacy analysis assessed the change in HbA(1c) from baseline using the per-protocol (PP) population.


RESULTS
For the PP cohort, mean baseline HbA(1c) was 7.3% in both groups. After 2 years, the least squares (LS) mean change in HbA(1c) from baseline [95% confidence interval (CI)] was -0.54% (-0.64, -0.45) with sitagliptin (n = 248) and -0.51% (-0.60, -0.42) with glipizide (n = 256). The rise in HbA(1c) from week 24 to week 104 [i.e. coefficient of durability (COD)] was smaller with sitagliptin [COD (95% CI) 0.16%/year (0.10, 0.21)] compared with glipizide [0.26%/year (0.21, 0.31)]. The proportion of patients with an HbA(1c)< 7% was 63% and 59% with sitagliptin and glipizide, respectively. The beta-cell responsiveness to a meal challenge was maintained with sitagliptin and decreased with glipizide. The proportion of patients who reported hypoglycaemia was 5% with sitagliptin and 34% with glipizide [difference in proportions (95% CI) = -29% (-33, -25)]. Relative to baseline, sitagliptin was associated with weight loss (-1.6 kg) compared with weight gain (+0.7 kg) with glipizide.


CONCLUSIONS
In patients with type 2 diabetes, adding sitagliptin to metformin monotherapy improved glycaemic control over 2 years, similar to the glucose-lowering efficacy observed with adding glipizide, but with greater durability and generally better maintenance of beta-cell function. Sitagliptin was generally well tolerated with a lower risk of hypoglycaemia and weight loss compared with weight gain observed with glipizide.
Seck
T
T
Merck Research Laboratories, Rahway, NJ, USA. thomas_seck@merck.com <thomas_seck@merck.com>
Nauck
M
M
Sheng
D
D
Sunga
S
S
Davies
M J
MJ
Stein
P P
PP
Kaufman
K D
KD
Amatruda
J M
JM
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D005913:Glipizide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D055815:Young Adult
D001786:Blood Glucose; D005913:Glipizide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles