Company: Bristol-Myers Squibb and AstraZeneca
Pharmacologic class: Dipeptidyl peptidase-4 (DPP4) inhibitor
Active ingredient: Saxagliptin 2.5 mg, 5 mg; tabs.
Indication: Adjunct to diet and exercise in type 2 diabetes, as monotherapy or combination therapy (see literature).
Pharmacology: In response to meals, the small intestine releases such incretin hormones as glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide into the bloodstream. These hormones, which cause the release of insulin from the pancreas, are quickly inactivated by DPP4. Also, pancreatic glucagon secretion is lowered by GLP-1.
Saxagliptin inhibits DPP4, thereby slowing down the inactivation of the incretin hormones, resulting in reduced fasting and postprandial glucose levels in a glucose- dependent manner in patients with type 2 diabetes mellitus. It may be used alone or with a sulfonylurea, metformin, or a thiazolidinedione. Saxagliptin has not been studied with insulin.
Clinical trials: The safety and efficacy of saxagliptin as monotherapy in the treatment of type 2 diabetes was evaluated in two 24-week, double-blind studies. In the first study, 401 patients were randomized to saxagliptin or placebo following a two-week lead-in phase. Patients who did not reach specific glycemic goals were treated with metformin rescue therapy added on to either placebo or saxagliptin. The efficacy was evaluated at the last measurement before rescue for patients needing metformin. Treatment with saxagliptin 2.5 mg/day and 5 mg/day resulted in significant improvements in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and two-hour postprandial glucose (PPG) compared with placebo. Significant improvements in HbA1c vs. placebo also occurred in the second monotherapy study.
The safety and efficacy of saxagliptin as add-on therapy to metformin, thiazolidinediones (pioglitazone, rosiglitazone), or glyburide was evaluated in three separate 24-week, randomized, double-blind trials. Saxagliptin 2.5 mg/day and 5 mg/day, added to each of these antidiabetic agents, resulted in significant improvements in HbA1c, FPG, and PPG, compared with placebo plus add-on therapy.
The use of metformin plus saxagliptin in 1,306 treatment-naive patients with type 2 diabetes was evaluated in a 24-week study. The coadministration of saxagliptin 5 mg plus metformin provided significant improvements in HbA1c, FPG, and PPG compared with placebo plus metformin.
Adults: 2.5 mg or 5 mg once daily. Moderate-severe renal impairment or end-stage renal disease requiring hemodialysis (creatinine clearance <50 mL/min), or concomitant strong CYP3A4/5 inhibitors: 2.5 mg once daily. Give dose after hemodialysis.
Children: Not recommended.
Precautions: Not for treating type 1 diabetes or diabetic ketoacidosis. Monitor renal function. Pregnancy (Cat. B). Nursing mothers.
Interactions: Potentiated by strong CYP3A4/5 inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Concomitant sulfonylurea: may need lower dose of sulfonylurea to reduce risk of hypoglycemia.
Adverse reactions: Upper respiratory tract infection, UTI, headache, GI upset; peripheral edema (with thiazolidinediones); hypoglycemia (with sulfonylureas); hypersensitivity reactions.
How supplied: Tabs 2.5 mg—30, 90 5 mg—30, 90, 100, 500
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