Rx Product News Profile: A Closer Look at New FDA Actions: Bristol-Myers Squibb's and AstraZeneca's Onglyza

Onglyza (saxagliptin) comarketed by Bristol-Myers Squibb and AstraZeneca, is FDA-approved to improve glycemic control for the treatment of type 2 diabetes.

Bristol-Myers Squibb’s and AstraZeneca’s Onglyza

The novel drug saxagliptin (Onglyza), comarketed by Bristol-Myers Squibb Co and AstraZeneca Pharmaceuticals LP, is FDA-approved for the treatment of type 2 diabetes mellitus (T2DM) in conjunction with diet and exercise as monotherapy or in combination with other oral antidiabetic agents to improve glycemic control.¹ According to the American Diabetes Association (ADA), diabetes affects more than 23.6 million children and adults, with T2DM affecting more than 90% of cases. Without proper early detection and treatment, patients have an increased risk for future cardiovascular events, such as heart disease and stroke or high blood pressure. Fortunately, a diet that follows ADA guidelines, exercise, and a patient-specific pharmacologic regimen may control desirable glycemic levels to provide patients with a better quality of life.²

Mechanism of Action

Saxagliptin is a potent, selective dipeptidylpeptidase-4 inhibitor that exerts its clinical effect by inhibiting incretin hormones, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, resulting in the stimulation of insulin secretion, decreasing glucagon secretion, improvement of beta cell function, and prolongation of gastric emptying time.^1,3

Clinical Trials

The role of saxagliptin in the treatment of T2DM in conjunction with diet and exercise as monotherapy or in combination with other antidiabetic agents to improve glycemic control was evaluated in a 24-week, randomized, double-blind, quadruple-arm, placebocontrolled study in 743 patients with T2DM and inadequate glycemic control. Eligible patients were given a lead-in dose of metformin 500 to 2550 mg for 2 weeks. Next, eligible patients were randomly assigned a 2.5-, 5-, or 10-mg dose of saxagliptin or placebo for the next 24 weeks. The primary end point measured included a change in baseline A1C to week 24. Statistically significant results indicate a reduction in A1C from baseline versus metformin plus placebo, with maximal reductions observed at week 12.⁴

Another clinical trial involved glucose- lowering activity of saxagliptin in drug-naïve patients with T2DM in a 12-week, multicenter, randomized, double-blind, placebo-controlled trial affecting 338 low-dose and 85 high-dose cohort patients. In all treatment arms, saxagliptin significantly reduced A1C by 0.7% to 0.9% from an average baseline of 7.9% versus placebo (0.3% reduction) in the low-dose cohort. Adverse effects were comparable across all treatment groups.⁵

Dosing

The dosing of saxagliptin for the treatment of T2DM in conjunction with diet and exercise as monotherapy or in combination with other antidiabetic agents to improve glycemic control includes a 2.5- to 5-mg tablet per oral route once daily. Patients taking strong cytochrome P450 (CYP) 3A4/5 inhibitors concomitantly, however, should reduce the saxagliptin dose to a 2.5-mg tablet per oral route once daily. Furthermore, a reduced dose of insulin secretagogues may be needed with concomitant use of saxagliptin. Saxagliptin has not been studied in combination with insulin and should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. The dose of saxagliptin in patients with moderate or severe renal impairment (creatinine clearance ≤50 mL/min) is a 2.5-mg tablet per oral route once daily. No hepatic adjustment is necessary. Pediatric dosing for efficacy and safety has not been established in patients 18 years of age or younger. No changes in dosing are necessary for the elderly.^1,3

Contraindications, Warnings, and Precautions

Saxagliptin is contraindicated in patients with a known hypersensitivity to any of its ingredients. Concomitant use with P-glycoprotein inhibitors or strong CYP3A4/5 inhibitors increases the serum concentration of saxagliptin, whereas concomitant use with P-glycoprotein inducers or strong CYP3A4/5 inducers decreases serum concentration of saxagliptin. Corticosteroids, somatropin, and thiazide diuretics may diminish the hypoglycemic effect of antidiabetic agents. Saxagliptin is in pregnancy category B and should not be used by patients who are breast-feeding, due to unknown lactation effects in breast milk. The most commonly reported adverse reactions include headache, hypoglycemia, peripheral edema, abdominal pain, vomiting, and sinusitis.^1,3 â– 

Dr. Challen is a clinical pharmacist specialist in primary care at Casa de Amigos Health Center in Houston, Texas. Ms. Ho is a 2010 PharmD candidate at Texas Southern University.

References

1. Saxagliptin drug information. FDA Web site. www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed January 27, 2010.

2. American Diabetes Association Web site. www.diabetes.org/. Accessed January 29, 2010.

3. Saxagliptin. Lexi-Comp Online. www.crlonline.com/crlsql/servlet/crlonline. Accessed January 29, 2010.

4. DeFronzo RA, Hissa MN, Garber AJ, et al; Saxagliptin 014 Study Group. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009;32(9)1649-1655.

5. Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naïve patients with type 2 diabetes. Diabetes Obes Metab. 2008;10(5):376-386. Epub 2008 Mar 18.