Saxagliptin Safe, Effective after 4 Years

San Diego—After examining 4-year extensions of 2 randomized, double-blind, placebo-controlled trials, researchers found that patients with type 2 diabetes who took saxagliptin alone or in combination with metformin tolerated the medication. They also demonstrated the efficacy of saxagliptin as add-on therapy to metformin for up to 3 years. The results were presented at the ADA meeting in a poster titled Long-Term Safety and Efficacy of Saxagliptin after 4-Year Follow-Up of Patients with Type 2 Diabetes. Saxagliptin, a dipeptidyl peptidase-4 inhibitor, is approved by the US Food and Drug Administration as an adjunct treatment with diet and exercise to improve glycemic control in patients with type 2 diabetes. In 2 previous 24-week trials, the drug was found to be superior to placebo when given as a monotherapy to treatment-naïve patients as well as an add-on therapy to metformin, thiazolidinedione, or sulfonylurea in patients who were inadequately controlled on monotherapy. Patients included in the study were between 18 and 77 years of age and had hemoglobin A1c (HbA1c) levels between 7.0% and 10.0%. When the short-term phase concluded, patients continued on the double-blind treatment for an additional 42 months. The study’s main efficacy end point was the time to discontinuation of the treatment or a rescue for lack of glycemic control. Patients received rescue medication if their HbA1c level was >8.0% at weeks 30, 37, and 50; if their HbA1c level was >7.5% at weeks 63 and 76; and if their HbA1c level was >7.0% at weeks 89 through 193. The rescue medication consisted of open-label metformin or pioglitazone added to the study medications. In the study comparing saxagliptin with placebo as monotherapy, 401 patients were treated, 336 entered the long-term phase, and 99 completed the 4 years of treatment. In the study comparing saxagliptin with placebo as add-on therapy, 743 patients were treated, 645 entered the long-term phase, and 229 completed the 4 years of treatment. According to the authors, patients treated with 2.5 mg, 5 mg, or 10 mg of saxagliptin as add-on therapy to metformin had a longer time to rescue or discontinuation from the therapy because of insufficient glycemic control compared with those given placebo as add-on therapy to metformin. Saxagliptin as add-on therapy was also associated with greater reductions in HbA1c level. In the saxagliptin monotherapy trial, patients who received placebo and did not have rescue for insufficient glycemic control switched to metformin after 24 weeks for the remainder of the study. Thus, the authors could not make efficacy comparisons in the long-term trial. Saxagliptin was well tolerated in both studies. In the monotherapy trial, 81.1% of patients in the placebo group had an adverse event (AE) compared with 87.3% in the 2.5-mg saxagliptin group, 88.7% in the 5-mg saxagliptin group, and 88.8% in the 10-mg saxagliptin group. In the add-on to the metformin therapy trial, 79.3% of patients in the placebo group had an AE compared with 92.2% in the 2.5-mg saxagliptin group, 81.2% in the 5-mg saxagliptin group, and 89.0% in the 10-mg saxagliptin group. The authors mentioned that most AEs were mild or moderate. The authors said that because of stringent rescue criteria, there were high rates of discontinuation, which limited the value of efficacy comparisons. In addition, they said that the limited data in the long-term phase for the change in HbA1c level hindered the authors’ ability to draw definitive conclusions. This study was supported by Bristol-Myers Squibb and AstraZeneca.