ST LOUIS (MD Consult) - On July 31, 2009, the US Food and Drug Administration (FDA) and the Bristol-Myers Squibb Co announced the approval of Onglyza (saxagliptin) for the treatment of type 2 diabetes mellitus in adults. Onglyza is a dipeptidyl peptidase-4 inhibitor, and it acts by stimulating the pancreas to produce more insulin postprandially.
Onglyza can be used in combination with commonly prescribed oral antidiabetic medications (eg, metformin, sulfonylureas, or thiazolidinediones [TZDs]) or as a monotherapy. The drug has not been studied in combination with insulin.
According to the manufacturer, the FDA approval of Onglyza was granted on the basis of clinical development program data. Trials involved approximately 5,000 patients, more than 4,000 of whom received Onglyza. As part of the development program, Onglyza, with diet and exercise, was studied as add-on therapy with other oral antidiabetic medications including metformin, the sulfonylurea glyburide, and TZDs. The drug was also studied as monotherapy. In addition, it was given to adult patients who had not been previously treated with antidiabetic medication. These patients received metformin and Onglyza in combination.
Throughout the phase 3 development program, treatment with Onglyza at all doses produced clinically relevant and statistically significant reductions in all 3 key measures of glucose control studied: hemoglobin A1c, fasting plasma glucose, and postprandial glucose. These improvements were evident when Onglyza was partnered with other commonly used oral antidiabetic agents or when the drug was used as monotherapy. Compared with placebo, Onglyza was weight and lipid neutral.
In clinical trials, the overall incidence of adverse effects for Onglyza at doses of 2.5 and 5 mg was similar to placebo (72% and 72.2% vs 70.6%, respectively). The most common adverse events reported with Onglyza 5 mg (≥5% and more commonly than placebo) were upper respiratory tract infection (7.7% vs 7.6%, respectively), urinary tract infection (6.8% vs 6.1%, respectively), and headache (6.5% vs 5.9%, respectively). In adult patients treated with Onglyza 2.5 mg, only headache (6.5%) was reported at ≥5% and more commonly than in adult patients treated with placebo. Discontinuation of therapy as a result of adverse events occurred in 2.2%, 3.3%, and 1.8% of patients receiving Onglyza 2.5 mg, Onglyza 5 mg, and placebo, respectively. A dose-related mean decrease in absolute lymphocyte count was observed in patients taking Onglyza.
The application seeking approval for Onglyza was submitted before the FDA recommended that manufacturers of new diabetes drugs design and evaluate their clinical trials for cardiovascular safety. In studies, Onglyza was not associated with an increased risk for cardiovascular events in patients who were mainly at low risk for these events. However, the FDA is requiring that a postmarketing study of patients at higher cardiovascular risk be carried out, with the intent of specifically evaluating cardiovascular safety in this population.
Onglyza is taken once daily, regardless of mealtime, at a dose of 2.5 or 5 mg. A dose of 2.5 mg is recommended for patients with moderate or severe renal impairment, or end-stage renal disease requiring hemodialysis. Onglyza has not been studied in patients undergoing peritoneal dialysis. Assessment of renal functio n is recommended before initiation of Onglyza therapy and periodically thereafter.
