.
In the study of JANUVIA as add-on combination therapy with metformin and rosiglitazone (Table 1), through Week 54 the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with JANUVIA and more commonly than in patients treated with placebo were: upper respiratory tract infection (JANUVIA, 15.5%; placebo, 6.2%), nasopharyngitis (11.0%, 9.3%), peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%).
In a pooled analysis of the two monotherapy studies, the add-on to metformin study, and the add-on to pioglitazone study, the incidence of selected gastrointestinal adverse reactions in patients treated with JANUVIA was as follows: abdominal pain (JANUVIA 100 mg, 2.3%; placebo, 2.1%), nausea (1.4%, 0.6%), and diarrhea (3.0%, 2.3%).
In an additional, 24-week, placebo-controlled factorial study of initial therapy with sitagliptin in combination with metformin, the adverse reactions reported (regardless of investigator assessment of causality) in ≥5% of patients are shown in Table 2.
Table 2: Initial Therapy with Combination of Sitagliptin and Metformin: Adverse Reactions Reported (Regardless of Investigator Assessment of Causality) in ≥5% of Patients Receiving Combination Therapy (and Greater than in Patients Receiving Metformin alone, Sitagliptin alone, and Placebo)*
Number of Patients (%)
* Intent-to-treat population. † Data pooled for the patients given the lower and higher doses of metformin.
Placebo
Sitagliptin
(JANUVIA)
100 mg QD
Metformin
500 or 1000 mg bid†
Sitagliptin
50 mg bid +
Metformin
500 or 1000 mg bid†
N = 176 N = 179 N = 364† N = 372†
Upper Respiratory Infection 9 (5.1) 8 (4.5) 19 (5.2) 23 (6.2)
Headache 5 (2.8) 2 (1.1) 14 (3.8) 22 (5.9)
In a 24-week study of initial therapy with JANUVIA in combination with pioglitazone, there were no adverse reactions reported (regardless of investigator assessment of causality) in ≥5% of patients and more commonly than in patients given pioglitazone alone.
No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed in patients treated with JANUVIA.
In a pooled analysis of 19 double-blind clinical trials that included data from 10,246 patients randomized to receive sitagliptin 100 mg/day (N=5429) or corresponding (active or placebo) control (N=4817), the incidence of acute pancreatitis was 0.1 per 100 patient-years in each group (4 patients with an event in 4708 patient-years for sitagliptin and 4 patients with an event in 3942 patient-years for control). [See WARNINGS AND PRECAUTIONS (5.1).]
Hypoglycemia
In all (N=9) studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia. A concurrent blood glucose measurement was not required although most (74%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When JANUVIA was coadministered with a sulfonylurea or with insulin, the percentage of patients with at least one adverse reaction of hypoglycemia was higher than in the corresponding placebo group (Table 3).
Table 3: Incidence and Rate of Hypoglycemia* in Placebo-Controlled Clinical Studies when JANUVIA was used as Add-On Therapy to Glimepiride (with or without Metformin) or Insulin (with or without Metformin), Regardless o |
