Initial sitagliptin plus metformin demonstrated to be effective in patients with type 2 diabetes

Key Points

Initial combination therapy with sitagliptin and metformin is more effective than either agent alone in lowering glucose values in patients with type 2 diabetes, according to the results of a study published in the journal Diabetes Care. Sitagliptin has previously demonstrated efficacy for the treatment of type 2 diabetes as monotherapy and in addition to metformin.

Treatment of type 2 diabetes with initial monotherapy is often unsuccessful in terms of reaching glycemic goals. Initial combination therapy is an alternative approach that can improve the odds of reaching glycemic goals and allow patients to avoid or delay subsequent treatment changes. Initial combination therapy may be most useful for patients with more marked hyperglycemia.

This randomized, double-blind, placebo-controlled, parallel-group study included 1,091 patients with type 2 diabetes and hemoglobin A_1c (HbA_1c) levels between 7.5% and 11% (average, 8.8%) who were not taking an oral antihyperglycemic agent for ≥8 weeks. The patients were randomized to 1 of 6 daily treatment groups for the 24-week study. The groups were 1) sitagliptin 100 mg plus metformin 1,000 mg (S100/M1,000); 2) sitagliptin 100 mg plus metformin 2,000 mg (S100/M2,000); 3) metformin 1,000 mg (M1,000); 4) metformin 2,000 mg (M2,000); 5) sitagliptin 100 mg (S100); or 6) placebo. The primary end point was the change in HbA_1c level from baseline after 24 weeks of treatment.

Treatment with any agent/combination of agents was associated with greater percentages of patients achieving HbA_1c levels <7% or <6.5% at Week 24 compared with placebo (P<.001 and P≤.005, respectively). A greater number of patients treated with combination therapy achieved these levels versus patients treated with monotherapy (P<.01); the combination of S100/M2,000 was associated with the greatest percentages of patients achieving these HbA_1c levels (<7%, 66%; <6.5%, 44%).

The study included an open-label cohort of 117 patients with HbA_1c levels >11% (mean, 11.2%) or a fasting glucose value >280 mg dL at baseline. These patients were treated with S100/M2,000 daily for 24 weeks and experienced a mean –2.9% reduction in HbA_1c levels (includes all patients). HbA_1c levels <7% were achieved in 22% of patients; 8% of patients achieved HbA_1c levels <6.5%. A total of 38 patients in this open-label study did not complete treatment (19 due to insufficient glycemic control). The mean decrease in HbA_1c levels among patients who completed the trial was –3.5% from baseline.

In general, all active treatments were well tolerated. Rates of hypoglycemia ranged from 0.6% to 2.2% in the treatment groups and were not significantly different from the rates associated with placebo.

SOURCE

Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; for the Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007 [Epub ahead of print].