Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes.
OBJECTIVE
To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [haemoglobin A(1c) (HbA(1c)) 7-11%] on metformin monotherapy.


METHODS
Patients (n = 273) on metformin (>/=1500 mg/day) were randomized to receive the addition of once-daily placebo, sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks. The efficacy analysis was based on the all-patients-treated population using an analysis of co-variance with change in HbA(1c) from baseline as the primary endpoint.


RESULTS
The mean baseline HbA(1c) was 7.7% for the entire cohort. After 18 weeks, both active add-on therapies led to greater improvements in HbA(1c) from baseline: -0.73% for sitagliptin (p < 0.001 vs. placebo) and -0.79% for rosiglitazone compared with -0.22% for placebo. No difference was observed between the sitagliptin and rosiglitazone treatments (0.06% [95% confidence interval (CI): -0.14 to 0.25]). The proportion of patients achieving an HbA(1c) < 7% was greater with sitagliptin (55%) and rosiglitazone (63%) compared with placebo (38%). Body weight increased from baseline with rosiglitazone (1.5 kg) compared with body weight reduction with sitagliptin (-0.4 kg) and placebo (-0.8 kg). The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg (95% CI: 1.3-2.5). In a prespecified analysis, the proportion of patients experiencing a greater than 3-kg increase in body weight was 21% in the rosiglitazone group compared with 2% in both the sitagliptin and placebo groups. Both active treatments were generally well tolerated, with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo.


CONCLUSIONS
In this 18-week study, the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Treatment with sitagliptin produced similar reductions in HbA(1c) compared with the addition of rosiglitazone.
Scott
R
R
Lipid and Diabetes Research Group, Christchurch School of Medicine, Christchurch, New Zealand.
Loeys
T
T
Davies
M J
MJ
Engel
S S
SS
D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008687:Metformin; D011719:Pyrazines; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; D014280:Triglycerides