First in DPP-4 inhibitor class cleared for diabetes

According to the manufacturer, sitagliptin inhibits the action of DPP-4 and slows inactivation of incretin hormones such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) that are involved in the regulation of glucose homeostasis.

Efficacy of sitagliptin as monotherapy was proven in two studies involving 473 patients treated for 24 weeks, and 296 patients who were treated for 18 weeks with 100 mg once-daily or placebo. Results showed a significant mean difference in A1C from placebo of -0.8% and -0.6%, respectively. When used as an add-on to either metformin or pioglitazone, results from 24-week studies showed that the addition of sitagliptin led to significant mean differences in A_1C from placebo of -0.7% in both drug arms.

Divine reminded pharmacists that treatment should always be based on the level of glycemic control needed, which can be determined by monitoring A_1C values. "Overall A_1C reduction with sitagliptin was 0.7% with greater reductions seen at higher baselines-for example, the reduction of 1.4% for baseline A_1C is ≥9%," she said. In addition, according to Merck, adding sitagliptin to metformin reduced postprandial glucose levels by 51 mg/dl and fasting plasma glucose by 25 mg/dl in a 24-week study compared with metformin alone.

Adverse reactions reported in ≥5% of patients taking sitagliptin included upper respiratory tract infections, headache, and nasopharyngitis.

Sitagliptin's place in therapy is yet to be fully established, Divine believes. "Due to several factors, such as cost and recent consensus algorithms, other agents-specifically metformin-are generally preferred as first-line therapy. This would indicate that sitagliptin may play more of a role as an add-on therapy," she explained. According to Merck, the price of sitagliptin will be $4.86 per tablet.