ct; § N = 201 N = 204
Baseline (mean) 257 271
Change from baseline (adjusted mean†) -49 -2
Difference from placebo (adjusted mean†)
(95% CI) -47‡
(-59, -34)
Additional Monotherapy Study
A multinational, randomized, double-blind, placebo-controlled study was also conducted to assess the safety and tolerability of JANUVIA in 91 patients with type 2 diabetes and chronic renal insufficiency (creatinine clearance <50 mL/min). Patients with moderate renal insufficiency received 50 mg daily of JANUVIA and those with severe renal insufficiency or with ESRD on hemodialysis or peritoneal dialysis received 25 mg daily. In this study, the safety and tolerability of JANUVIA were generally similar to placebo. A small increase in serum creatinine was reported in patients with moderate renal insufficiency treated with JANUVIA relative to those on placebo. In addition, the reductions in A1C and FPG with JANUVIA compared to placebo were generally similar to those observed in other monotherapy studies. [See CLINICAL PHARMACOLOGY (12.3).]
14.2 Combination Therapy
Add-on Combination Therapy with Metformin
A total of 701 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 metformin. Patients already on metformin (N=431) at a dose of at least 1500 mg per day were randomized after completing a 2-week single-blind placebo run-in period. Patients on metformin and another antihyperglycemic agent (N=229) and patients not on any antihyperglycemic agents (off therapy for at least 8 weeks, N=41) were randomized after a run-in period of approximately 10 weeks on metformin (at a dose of at least 1500 mg per day) in monotherapy. Patients with inadequate glycemic control (A1C 7% to 10%) 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 metformin, JANUVIA provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo with metformin (Table 5). Rescue glycemic therapy was used in 5% of patients treated with JANUVIA 100 mg and 14% of patients treated with placebo. A similar decrease in body weight was observed for both treatment groups.
Table 5: Glycemic Parameters at Final Visit (24-Week Study) for JANUVIA in Add-on Combination Therapy with Metformin*
JANUVIA 100 mg + Metformin Placebo + Metformin
* Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy. † Least squares means adjusted for prior antihyperglycemic therapy and baseline value. ‡ p<0.001 compared to placebo + metformin.
A1C (%) N = 453 N = 224
Baseline (mean) 8.0 8.0
Change from baseline (adjusted mean†) -0.7 -0.0
Difference from placebo + metformin (adjusted mean†)
(95% CI) -0.7‡
(-0.8, -0.5)
Patients (%) achieving A1C <7% 213 (47%) 41 (18%)
FPG (mg/dL) N = 454 N = 226
Baseline (mean) 170 174
Change from baseline (adjusted mean†) -17 9
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