f Investigator Assessment of Causality
Add-On to Glimepiride
(+/- Metformin) (24 weeks)
JANUVIA 100 mg
+ Glimepiride
(+/- Metformin)
Placebo
+ Glimepiride
(+/- Metformin)
* Adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required; intent-to-treat population. † Based on total number of events (i.e., a single patient may have had multiple events). ‡ Severe events of hypoglycemia were defined as those events requiring medical assistance or exhibiting depressed level/loss of consciousness or seizure.
N = 222 N = 219
Overall (%) 27 (12.2) 4 (1.8)
Rate (episodes/patient-year)† 0.59 0.24
Severe (%)‡ 0 (0.0) 0 (0.0)
Add-On to Insulin
(+/- Metformin) (24 weeks)
JANUVIA 100 mg
+ Insulin
(+/- Metformin)
Placebo
+ Insulin
(+/- Metformin)
N = 322 N = 319
Overall (%) 50 (15.5) 25 (7.8)
Rate (episodes/patient-year)† 1.06 0.51
Severe (%)‡ 2 (0.6) 1 (0.3)
In a pooled analysis of the two monotherapy studies, the add-on to metformin study, and the add-on to pioglitazone study, the overall incidence of adverse reactions of hypoglycemia was 1.2% in patients treated with JANUVIA 100 mg and 0.9% in patients treated with placebo.
In the study of JANUVIA as add-on combination therapy with metformin and rosiglitazone, the overall incidence of hypoglycemia was 2.2% in patients given add-on JANUVIA and 0.0% in patients given add-on placebo through Week 18. Through Week 54, the overall incidence of hypoglycemia was 3.9% in patients given add-on JANUVIA and 1.0% in patients given add-on placebo.
In the 24-week, placebo-controlled factorial study of initial therapy with JANUVIA in combination with metformin, the incidence of hypoglycemia was 0.6% in patients given placebo, 0.6% in patients given JANUVIA alone, 0.8% in patients given metformin alone, and 1.6% in patients given JANUVIA in combination with metformin.
In the study of JANUVIA as initial therapy with pioglitazone, one patient taking JANUVIA experienced a severe episode of hypoglycemia. There were no severe hypoglycemia episodes reported in other studies except in the study involving coadministration with insulin.
Laboratory Tests
Across clinical studies, the incidence of laboratory adverse reactions was similar in patients treated with JANUVIA 100 mg compared to patients treated with placebo. A small increase in white blood cell count (WBC) was observed due to an increase in neutrophils. This increase in WBC (of approximately 200 cells/microL vs placebo, in four pooled placebo-controlled clinical studies, with a mean baseline WBC count of approximately 6600 cells/microL) is not considered to be clinically relevant. In a 12-week study of 91 patients with chronic renal insufficiency, 37 patients with moderate renal insufficiency were randomized to JANUVIA 50 mg daily, while 14 patients with the same magnitude of renal impairment were randomized to placebo. Mean (SE) increases in serum creatinine were observed in patients treated with JANUVIA [0.12 mg/dL (0.04)] and in patients treated with placebo [0.07 mg/dL (0.07)]. The clinical significance of this added increase in serum creatinine relative to placebo is not known.
6.2 Postmarket
