designed to assess the efficacy of JANUVIA in combination with metformin and rosiglitazone. Patients on dual therapy with metformin ≥1500 mg/day and rosiglitazone ≥4 mg/day or with metformin ≥1500 mg/day and pioglitazone ≥30 mg/day (switched to rosiglitazone ≥4 mg/day) entered a dose-stable run-in period of 6 weeks. Patients on other dual therapy were switched to metformin ≥1500 mg/day and rosiglitazone ≥4 mg/day in a dose titration/stabilization run-in period of up to 20 weeks in duration. After the run-in period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized 2:1 to the addition of either 100 mg of JANUVIA or placebo, administered once daily. Patients who failed to meet specific glycemic goals during the study were treated with glipizide (or other sulfonylurea) rescue. The primary time point for eva luation of glycemic parameters was Week 18.
In combination with metformin and rosiglitazone, JANUVIA provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo with metformin and rosiglitazone (Table 10) at Week 18. At Week 54, mean reduction in A1C was -1.0% for patients treated with JANUVIA and -0.3% for patients treated with placebo in an analysis based on the intent-to-treat population. Rescue therapy was used in 18% of patients treated with JANUVIA 100 mg and 40% of patients treated with placebo. There was no significant difference between JANUVIA and placebo in body weight change.
Table 10: Glycemic Parameters at Week 18 for JANUVIA in Add-on Combination Therapy with Metformin and Rosiglitazone*
JANUVIA 100 mg + Metformin + Rosiglitazone
Placebo +
Metformin + Rosiglitazone
* Intent-to-treat population using last observation on study prior to glipizide (or other sulfonylurea) rescue therapy. † Least squares means adjusted for prior antihyperglycemic therapy status and baseline value. ‡ p<0.001 compared to placebo + metformin + rosiglitazone.
A1C (%) N = 176 N = 93
Baseline (mean) 8.8 8.7
Change from baseline (adjusted mean†) -1.0 -0.4
Difference from placebo + rosiglitazone + metformin (adjusted mean†) (95% CI) -0.7‡
(-0.9, -0.4)
Patients (%) achieving A1C <7% 39 (22%) 9 (10%)
FPG (mg/dL) N = 179 N = 94
Baseline (mean) 181 182
Change from baseline (adjusted mean†) -30 -11
Difference from placebo + rosiglitazone + metformin (adjusted mean†) (95% CI) -18‡
(-26, -10)
2-hour PPG (mg/dL) N = 152 N = 80
Baseline (mean) 256 248
Change from baseline (adjusted mean†) -59 -21
Difference from placebo + rosiglitazone + metformin (adjusted mean†) (95% CI) -39‡
(-51, -26)
Add-on Combination Therapy with Glimepiride, with or without Metformin
A total of 441 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of JANUVIA in combination with glimepiride, with or without metformin. Patients en |
