FDA Approvals: Janumet

April 12, 2007 — The US Food and Drug Administration (FDA) has approved sitagliptin plus metformin HCl tablets for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled with either component alone or those already being treated with the drug combination.
Sitagliptin Plus Metformin HCl Tablets (Janumet) for Management of Type 2 Diabetes
On March 30, the FDA approved sitagliptin plus metformin HCl tablets (Janumet; Merck & Co Inc) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus who are inadequately controlled with either component alone or who are already receiving both components separately.
Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor and acts by increasing the body's active incretin hormone levels, thereby triggering the pancreas to increase insulin and signaling the liver to stop glucose production. Adding sitagliptin to an insulin sensitizer such as metformin therefore addresses the 3 key defects of type 2 diabetes: insulin resistance, β-cell dysfunction, and α-cell dysfunction.
Approval of the combination product was based on data from a 24-week double-blind study (n = 701) in which patients were randomized to receive add-on treatment with either 100 mg of sitagliptin (n = 453) or placebo (n = 224) after an initial run-in period of metformin monotherapy (minimum dosage, 1500 mg/day). Pioglitazone rescue was used for those who did not meet specific glycemic goals during the study.
Results showed that the addition of sitagliptin to metformin yielded significant improvements from baseline in mean hemoglobin A1c levels (-0.7% vs -0.0%; change = -0.7%; 95% confidence interval [CI], -0.8% to -0.5%; P < .001). In the study, more than twice as many patients receiving sitagliptin add-on therapy achieved a hemoglobin A1c goal of less than 7% compared with those receiving metformin alone (47% vs 18%; P < .001).
Use of the combination product also provided 24-hour glucose response, as demonstrated by significant improvements in fasting plasma glucose (-17 vs +9 mg/dL; change = -25 mg/dL; 95% CI, -31 to -20 mg/dL) and 2-hour postprandial glucose levels (-62 vs -11 mg/dL; change = -51 mg/dL; 95% CI, -61 to -41 mg/dL), compared with metformin alone (P < .001, both). Rescue glycemic therapy was required only by 5% of patients receiving sitagliptin plus metformin compared with 14% of those receiving metformin alone.
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