Saxagliptin

Usual Dosing (Adults)

CLINICAL PHARMACOLOGY
Mechanism of Action:
Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the dipeptidyl peptidase-4 (DPP4) enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.

INDICATIONS AND USAGE
Monotherapy and Combination Therapy:
ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings.

Important Limitations of Use:
ONGLYZA should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.

DOSAGE AND ADMINISTRATION
Recommended Dosing:
The recommended dose of ONGLYZA is 2.5 mg or 5 mg once daily taken regardless of meals.

Renal Dosing

Patients with Renal Impairment:
No dosage adjustment for ONGLYZA is recommended for patients with mild renal impairment (creatinine clearance [CrCl] >50 mL/min).

The dose of ONGLYZA is 2.5 mg once daily for patients with moderate or severe renal impairment, or with end-stage renal disease (ESRD) requiring hemodialysis (creatinine clearance [CrCl] ≤50 mL/min. ONGLYZA should be administered following hemodialysis. ONGLYZA has not been studied in patients undergoing peritoneal dialysis.

Because the dose of ONGLYZA should be limited to 2.5 mg based upon renal function, assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter. Renal function can be estimated from serum creatinine using the Cockcroft-Gault formula or Modification of Diet in Renal Disease formula.

Hemodialysis

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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