tered a run-in treatment period on glimepiride (≥4 mg per day) alone or glimepiride in combination with metformin (≥1500 mg per day). After a dose-titration and dose-stable run-in period of up to 16 weeks and a 2-week placebo run-in period, patients with inadequate glycemic control (A1C 7.5% to 10.5%) were randomized to the addition of either 100 mg of JANUVIA or placebo, administered once daily. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue.
In combination with glimepiride, with or without metformin, JANUVIA provided significant improvements in A1C and FPG compared to placebo (Table 11). In the entire study population (patients on JANUVIA in combination with glimepiride and patients on JANUVIA in combination with glimepiride and metformin), a mean reduction from baseline relative to placebo in A1C of -0.7% and in FPG of -20 mg/dL was seen. Rescue therapy was used in 12% of patients treated with JANUVIA 100 mg and 27% of patients treated with placebo. In this study, patients treated with JANUVIA had a mean increase in body weight of 1.1 kg vs. placebo (+0.8 kg vs. -0.4 kg). In addition, there was an increased rate of hypoglycemia. [See WARNINGS AND PRECAUTIONS (5.3); ADVERSE REACTIONS (6.1).]
Table 11: Glycemic Parameters at Final Visit (24-Week Study) for JANUVIA as Add-On Combination Therapy with Glimepiride, with or without Metformin*
JANUVIA 100 mg
+ Glimepiride Placebo +
Glimepiride JANUVIA 100 mg
+ Glimepiride
+ Metformin Placebo
+ Glimepiride
+ Metformin
* Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy. † Least squares means adjusted for prior antihyperglycemic therapy status and baseline value. ‡ p<0.001 compared to placebo. § p<0.01 compared to placebo.
A1C (%) N = 102 N = 103 N = 115 N = 105
Baseline (mean) 8.4 8.5 8.3 8.3
Change from baseline (adjusted mean†) -0.3 0.3 -0.6 0.3
Difference from placebo (adjusted mean†)
(95% CI) -0.6‡
(-0.8, -0.3) -0.9‡
(-1.1, -0.7)
Patients (%) achieving A1C <7% 11 (11%) 9 (9%) 26 (23%) 1 (1%)
FPG (mg/dL) N = 104 N = 104 N = 115 N = 109
Baseline (mean) 183 185 179 179
Change from baseline (adjusted mean†) -1 18 -8 13
Difference from placebo (adjusted mean†)
(95% CI) -19§
(-32, -7) -21‡
(-32, -10)
Add-on Combination Therapy with Insulin (with or without Metformin)
A total of 641 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of JANUVIA as add-on to insulin therapy (with or without metformin). The racial distribution in this study was approximately 70% white, 18% Asian, 7% black, and 5% other groups. Approximately 14% of the patients in this study were Hispanic. Patients entered a 2-week, single-blind run-in treatment period on pre-mixed, long-acting, or intermediate-acting insulin, with or without metformin (≥1500 mg per day). Patients using short-acting insulins were excluded unless the short-acting insulin was administered a |
