ble 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 of 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 (%)&Dagge |
