Difference from placebo + metformin (adjusted mean†)
(95% CI) -25‡
(-31, -20)
2-hour PPG (mg/dL) N = 387 N = 182
Baseline (mean) 275 272
Change from baseline (adjusted mean†) -62 -11
Difference from placebo + metformin (adjusted mean†)
(95% CI) -51‡
(-61, -41)
Initial Combination Therapy with Metformin
A total of 1091 patients with type 2 diabetes and inadequate glycemic control on diet and exercise participated in a 24-week, randomized, double-blind, placebo-controlled factorial study designed to assess the efficacy of sitagliptin as initial therapy in combination with metformin. Patients on an antihyperglycemic agent (N=541) discontinued the agent, and underwent a diet, exercise, and drug washout period of up to 12 weeks duration. After the washout period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized after completing a 2-week single-blind placebo run-in period. Patients not on antihyperglycemic agents at study entry (N=550) with inadequate glycemic control (A1C 7.5% to 11%) immediately entered the 2-week single-blind placebo run-in period and then were randomized. Approximately equal numbers of patients were randomized to receive initial therapy with placebo, 100 mg of JANUVIA once daily, 500 mg or 1000 mg of metformin twice daily, or 50 mg of sitagliptin twice daily in combination with 500 mg or 1000 mg of metformin twice daily. Patients who failed to meet specific glycemic goals during the study were treated with glyburide (glibenclamide) rescue.
Initial therapy with the combination of JANUVIA and metformin provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo, to metformin alone, and to JANUVIA alone (Table 6, Figure 1). Mean reductions from baseline in A1C were generally greater for patients with higher baseline A1C values. For patients not on an antihyperglycemic agent at study entry, mean reductions from baseline in A1C were: JANUVIA 100 mg once daily, -1.1%; metformin 500 mg bid, -1.1%; metformin 1000 mg bid, -1.2%; sitagliptin 50 mg bid with metformin 500 mg bid, -1.6%; sitagliptin 50 mg bid with metformin 1000 mg bid, -1.9%; and for patients receiving placebo, -0.2%. Lipid effects were generally neutral. The decrease in body weight in the groups given sitagliptin in combination with metformin was similar to that in the groups given metformin alone or placebo.
Table 6: Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin and Metformin, Alone and in Combination as Initial Therapy*
Placebo
Sitagliptin
(JANUVIA)
100 mg QD
Metformin
500 mg bid Metformin
1000 mg bid Sitagliptin
50 mg bid +
Metformin
500 mg bid Sitagliptin
50 mg bid +
Metformin
1000 mg bid
* Intent-to-treat population using last observation on study prior to glyburide (glibenclamide) rescue therapy. † Least squares means adjusted for prior antihyperglycemic therapy status and baseline value. ‡ p<0.001 compared to placebo.
A1C (%) N = 165 N = 175 N = 178 N = 177 N = 183 N = 178
Baseline (mean) 8.7 8.9 8.9 8.7 8.8 8.8
Change from baseline (adjusted mean†) 0.2 -0.7 -0.8 -1.1 -1.4 -1.9
Difference from placeb |
