t 18 weeks duration. Incidences of hypoglycemia are shown in Table 4.
Table 2 Placebo-Controlled Clinical Studies of Sitagliptin 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) Sitagliptin 100 mg Placebo
N = 443 N = 363
Nasopharyngitis 23 (5.2) 12 (3.3)
Combination with Pioglitazone (24 weeks) Sitagliptin 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) Sitagliptin 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) Sitagliptin 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 sitagliptin 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 sitagliptin 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 4).
In the study of sitagliptin as add-on combination therapy with metformin and rosiglitazone (Table 2), through Week 54 the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: upper respiratory tract infection (sitagliptin, 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 sitagliptin was as follows: abdominal pain (sitagliptin 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 3.
Table 3 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 (%)
Placebo Sitagliptin
100 mg QD
Metformin
500 or 1000 mg bid † Sitagliptin
50 mg bid +
Metfor |
