50 mg bid +

Metformin 500 mg/

Metformin 1000 mg bid†
 
 N = 176 N = 179 N = 364† N = 372†
*
Intent-to-treat population.
†
Data pooled for the patients given the lower and higher doses of metformin.
Diarrhea 7 (4.0) 5 (2.8) 28 (7.7) 28 (7.5)
Upper Respiratory Tract 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)

Sitagliptin Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled on Metformin Alone

In a 24-week placebo-controlled trial of sitagliptin 100mg administered once daily added to a twice daily metformin regimen, there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo. Discontinuation of therapy due to clinical adverse reactions was similar to the placebo treatment group (sitagliptin and metformin, 1.9%; placebo and metformin, 2.5%).

Gastrointestinal Adverse Reactions

The incidences of pre-selected gastrointestinal adverse experiences in patients treated with sitagliptin and metformin were similar to those reported for patients treated with metformin alone. See Table 2.

Table 2: Pre-selected Gastrointestinal Adverse Reactions (Regardless of Investigator Assessment of Causality) Reported in Patients with Type 2 Diabetes Receiving Sitagliptin and Metformin  Number of Patients (%)
 Study of Sitagliptin and Metformin in Patients Inadequately Controlled on Diet and Exercise Study of Sitagliptin Add-on in Patients Inadequately Controlled on Metformin Alone
 Placebo
 Sitagliptin

100 mg QD
 Metformin 500 mg/

Metformin 1000 mg bid*
 Sitagliptin

50 mg bid +

Metformin 500 mg/

Metformin 1000 mg bid*
 Placebo and Metformin

≥1500mg daily Sitagliptin 100mg QD and Metformin

≥1500mg daily
 N = 176 N = 179 N = 364 N = 372 N = 237 N = 464
*
Data pooled for the patients given the lower and higher doses of metformin.
†
Abdominal discomfort was included in the analysis of abdominal pain in the study of initial therapy.
Diarrhea 7 (4.0) 5 (2.8) 28 (7.7) 28 (7.5) 6 (2.5) 11 (2.4)
Nausea 2 (1.1) 2 (1.1) 20 (5.5) 18 (4.8) 2 (0.8) 6 (1.3)
Vomiting 1 (0.6) 0 (0.0) 2 (0.5) 8 (2.2) 2 (0.8) 5 (1.1)
Abdominal Pain† 4 (2.3) 6 (3.4) 14 (3.8) 11 (3.0) 9 (3.8) 10 (2.2)

Sitagliptin in Combination with Metformin and Glimepiride

In a 24-week placebo-controlled study of sitagliptin 100mg as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin and glimepiride (sitagliptin, N=116; placebo, N=113), 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: hypoglycemia (Table 3) and headache (6.9%, 2.7%).

Sitagliptin in Combination with Metformin and Rosiglitazone

In a placebo-controlled study of sitagliptin 100mg as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin and rosiglitazone (sitagliptin, N=181; placebo, N=97), the adverse reactions reported regardless of investigator assessment of causality through Week 18 in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: upper respira