I. As is typical for trials of agents to treat type 2 diabetes, the mean reduction in A1C with JANUVIA appears to be related to the degree of A1C elevation at baseline. In these 18- and 24-week studies, among patients who were not on an antihyperglycemic agent at study entry, the reductions from baseline in A1C were -0.7% and -0.8%, respectively, for those given JANUVIA, and -0.1% and -0.2%, respectively, for those given placebo. Overall, the 200 mg daily dose did not provide greater glycemic efficacy than the 100 mg daily dose. The effect of JANUVIA on lipid endpoints was similar to placebo. Body weight did not increase from baseline with JANUVIA therapy in either study, compared to a small reduction in patients given placebo.
Table 4: Glycemic Parameters in 18- and 24-Week Placebo-Controlled Studies of JANUVIA in Patients with Type 2 Diabetes* 18-Week Study 24-Week Study
JANUVIA 100 mg Placebo JANUVIA 100 mg Placebo
* Intent-to-treat population using last observation on study prior to metformin rescue therapy. † Least squares means adjusted for prior antihyperglycemic therapy status and baseline value. ‡ p<0.001 compared to placebo. § Data not available.
A1C (%) N = 193 N = 103 N = 229 N = 244
Baseline (mean) 8.0 8.1 8.0 8.0
Change from baseline (adjusted mean†) -0.5 0.1 -0.6 0.2
Difference from placebo (adjusted mean†)
(95% CI) -0.6‡
(-0.8, -0.4) -0.8‡
(-1.0, -0.6)
Patients (%) achieving A1C <7% 69 (36%) 16 (16%) 93 (41%) 41 (17%)
FPG (mg/dL) N = 201 N = 107 N = 234 N = 247
Baseline (mean) 180 184 170 176
Change from baseline (adjusted mean†) -13 7 -12 5
Difference from placebo (adjusted mean†)
(95% CI) -20‡
(‑31, -9) -17‡
(‑24, -10)
2-hour PPG (mg/dL) § § 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 TherapyAdd-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 |
