ormin, the overall incidence of adverse reactions, hypoglycemia, and discontinuation of therapy due to clinical adverse reactions with JANUVIA were similar to placebo. In combination with glimepiride, with or without metformin, the overall incidence of clinical adverse reactions with JANUVIA was higher than with placebo, in part related to a higher incidence of hypoglycemia (see Table 3); the incidence of discontinuation due to clinical adverse reactions was similar to placebo.
Two placebo-controlled monotherapy studies, one of 18- and one of 24-week duration, included patients treated with JANUVIA 100 mg daily, JANUVIA 200 mg daily, and placebo. Five placebo-controlled add-on combination therapy studies were also conducted: one with metformin; one with pioglitazone; one with metformin and rosiglitazone; one with glimepiride (with or without metformin); and one with insulin (with or without metformin). In these trials, patients with inadequate glycemic control on a stable dose of the background therapy were randomized to add-on therapy with JANUVIA 100 mg daily or placebo. The adverse reactions, excluding hypoglycemia, reported regardless of investigator assessment of causality in ≥5% of patients treated with JANUVIA 100 mg daily and more commonly than in patients treated with placebo, are shown in Table 1 for the clinical trials of at least 18 weeks duration. Incidences of hypoglycemia are shown in Table 3.
Table 1: Placebo-Controlled Clinical Studies of JANUVIA Monotherapy or Add-on Combination Therapy with Pioglitazone, Metformin + Rosiglitazone, or Glimepiride +/- Metformin: Adverse Reactions (Excluding Hypoglycemia) Reported in ≥5% of Patients and More Commonly than in Patients Given Placebo, Regardless of Investigator Assessment of Causality*
Number of Patients (%)
* Intent-to-treat population
Monotherapy (18 or 24 weeks) JANUVIA 100 mg Placebo
N = 443 N = 363
Nasopharyngitis 23 (5.2) 12 (3.3)
Combination with Pioglitazone
(24 weeks)
JANUVIA 100 mg +
Pioglitazone
Placebo +
Pioglitazone
N = 175 N = 178
Upper Respiratory Tract Infection 11 (6.3) 6 (3.4)
Headache 9 (5.1) 7 (3.9)
Combination with Metformin +
Rosiglitazone (18 weeks)
JANUVIA 100 mg +
Metformin + Rosiglitazone
Placebo +
Metformin + Rosiglitazone
N = 181 N = 97
Upper Respiratory Tract Infection 10 (5.5) 5 (5.2)
Nasopharyngitis 11 (6.1) 4 (4.1)
Combination with Glimepiride
(+/- Metformin) (24 weeks)
JANUVIA 100 mg
+ Glimepiride
(+/- Metformin)
Placebo
+ Glimepiride
(+/- Metformin)
N = 222 N = 219
Nasopharyngitis 14 (6.3) 10 (4.6)
Headache 13 (5.9) 5 (2.3)
In the 24-week study of patients receiving JANUVIA as add-on combination therapy with metformin, there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo.
In the 24-week study of patients receiving JANUVIA as add-on therapy to insulin (with or without metformin), there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo, except for hypoglycemia (see Table 3) |
