The combination of sitagliptin/metformin is now approved by FDA to improve glycemic control in adult patients with type 2 diabetes mellitus.
MERCKCombination of sitagliptin and metformin to improve glycemic control in adult patients with type 2 diabetes mellitus
This treatment combines 2 antihyperglycemic agents with complementary mechanisms of action: sitagliptin, an inhibitor of the dipeptidyl peptidase-4 enzyme, and metformin, a member of the biguanide class. This combination was approved on March 30, 2007, as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus whose disease is not adequately controlled with metformin or sitagliptin alone or in patients already being treated concurrently with sitagliptin and metformin.
Efficacy. The effectiveness of this combination has not been specifically studied in clinical efficacy trials, but the bioequivalence of the combination has been demonstrated. A total of 701 patients with type 2 diabetes mellitus were enrolled in a 24-week, randomized, double-blind, placebo-controlled study. Patients already taking metformin ≥1,500 mg/d (n=431) were randomized after a 2-week, single-blind, placebo run-in period. Patients taking metformin and another antihyperglycemic agent (n=229) and patients not taking any antihyperglycemic agents for ≥8 weeks (n=41) were randomized after receiving metformin ≥1,500 mg/d during a run-in period of approximately 10 weeks. Patients were randomized to receive sitagliptin 100 mg/d or placebo concurrently with metformin. The combination of sitagliptin and metformin demonstrated significant improvements in HbA1C (sitagliptin/metformin change from baseline relative to placebo/metformin, –0.7%; 95% CI, –0.8% to –0.5%; P<.001), fasting plasma glucose (sitagliptin/metformin change from baseline relative to placebo/metformin, –25 mg/dL; 95% CI, –31 to –20; P<.001), and 2-hour postprandial glucose (sitagliptin/metformin change from baseline relative to placebo/metformin, –51 mg/dL; 95% CI, –61 to –41; P<.001).
Dosing. The dose of this combination should be individualized according to the patient's current drug regimen, effectiveness, and tolerability; the dose should not exceed the maximum recommended daily dose of sitagliptin 100 mg/metformin 2,000 mg. The combination should be administered BID with meals, with gradual dose escalation, to reduce possible gastrointestinal side effects. For patients whose diabetes is not adequately controlled with metformin monotherapy, the starting dose should be sitagliptin 100 mg/d plus the patient's current dose of metformin. Patients currently taking metformin 850 mg BID should be administered sitagliptin 50 mg/metformin 1,000 mg BID. For patients whose diabetes is not adequately controlled with sitagliptin monotherapy, the starting dose should be sitagliptin 50 mg/metformin 500 mg BID. Patients may then be titrated to sitagliptin 50 mg/metformin 1,000 mg BID. For patients currently taking sitagliptin concurrently with metformin, the combination may be initiated at the patient's current dose.