s part of a pre-mixed insulin. After the run-in period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized to the addition of either 100 mg of JANUVIA or placebo, administered once daily. Patients were on a stable dose of insulin prior to enrollment with no changes in insulin dose permitted during the run-in period. Patients who failed to meet specific glycemic goals during the double-blind treatment period were to have uptitration of the background insulin dose as rescue therapy.
The median daily insulin dose at baseline was 42 units in the patients treated with JANUVIA and 45 units in the placebo-treated patients. The median change from baseline in daily dose of insulin was zero for both groups at the end of the study. In combination with insulin (with or without metformin), JANUVIA provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo (Table 12). Both treatment groups had an adjusted mean increase in body weight of 0.1 kg from baseline to Week 24. There was an increased rate of hypoglycemia in patients treated with JANUVIA. [See WARNINGS AND PRECAUTIONS (5.3); ADVERSE REACTIONS (6.1).]
Table 12: Glycemic Parameters at Final Visit (24-Week Study) for JANUVIA as Add-on Combination Therapy with Insulin*
JANUVIA 100 mg
+ Insulin
(+/- Metformin)
Placebo +
Insulin
(+/- Metformin)
* Intent-to-treat population using last observation on study prior to rescue therapy. † Least squares means adjusted for metformin use at the screening visit (yes/no), type of insulin used at the screening visit (pre-mixed vs. non-pre-mixed [intermediate- or long-acting]), and baseline value. ‡ Treatment by stratum interaction was not significant (p>0.10) for metformin stratum and for insulin stratum. § p<0.001 compared to placebo.
A1C (%) N = 305 N = 312
Baseline (mean) 8.7 8.6
Change from baseline (adjusted mean†) -0.6 -0.1
Difference from placebo (adjusted mean†,‡) (95% CI) -0.6§
(-0.7, -0.4)
Patients (%) achieving A1C <7% 39 (12.8%) 16 (5.1%)
FPG (mg/dL) N = 310 N = 313
Baseline (mean) 176 179
Change from baseline (adjusted mean†) -18 -4
Difference from placebo (adjusted mean†) (95% CI) -15§
(-23, -7)
2-hour PPG (mg/dL) N = 240 N = 257
Baseline (mean) 291 292
Change from baseline (adjusted mean†) -31 5
Difference from placebo (adjusted mean†) (95% CI) -36§
(-47, -25) CLOSE
16 HOW SUPPLIED/STORAGE AND HANDLING
No. 6737 — Tablets JANUVIA, 25 mg, are pink, round, film-coated tablets with "221" on one side. They are supplied as follows:
NDC 0006-0221-31 unit-of-use bottles of 30
NDC 0006-0221-54 unit-of-use bottles of 90
NDC 0006-0221-28 unit dose blister packages of 100.
No. 6738 — Tablets JANUVIA, 50 mg, are light beige, round, film-coated tablets with "112" on one side. They are supplied as follows:
NDC 0006-0112-31 unit-of-use bottles of 30
NDC
