Product: Kombiglyze XR 5/500

Company: Bristol-Myers Squibb

Pharmacologic class: Antidiabetic (dipeptidyl peptidase-4 (DPP4) inhibitor + biguanide)

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Active ingredients: Saxagliptin 5 mg, metformin HCl extended-release 500 mg; tablets.

Also: Kombiglyze XR 5/1,000

Active ingredients: Saxagliptin 5 mg, metformin HCl extended-release 1,000 mg; tablets.

Also: Kombiglyze XR 2.5/1,000

Active ingredients: Saxagliptin 2.5 mg, metformin HCl extended-release 1,000 mg; tablets.

Indication: Adjunct to diet and exercise in type 2 diabetes when treatment with both saxagliptin and metformin is appropriate.

Pharmacology: Kombiglyze XR is an antidiabetic product that combines a DPP4 inhibitor and extended-release form of the biguanide, metformin. Saxagliptin slows the inactivation of incretin hormones, increasing their levels in the blood, leading to reduced fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels in a glucose-dependent manner. Metformin improves glucose tolerance in type 2 diabetes by decreasing hepatic glucose production and intestinal absorption of glucose, and by improving insulin sensitivity; it generally does not cause hypoglycemia.

Kombiglyze XR has not been studied in combination with insulin.

Clinical trials: A study involving treatment-naive patients with type 2 diabetes who had inadequate glycemic control on diet and exercise was conducted to evaluate the safety and efficacy of saxagliptin + metformin immediate-release. Coadministration of saxagliptin 5 mg/day plus metformin resulted in significant improvements in hemoglobin (Hb)A1c, fasting plasma glucose, and two-hour postprandial glucose compared with placebo plus metformin.

In another study, saxagliptin 2.5 mg and 5 mg was given as add-on therapy to patients with inadequate glycemic control on metformin immediate-release alone. This combination provided significant improvements in HbA1c, FPG, and PPG compared with placebo add-on to metformin immediate-release.

Adults: Take once daily with evening meal. Swallow whole. Individualize; titrate based on response. Maximum saxagliptin 5 mg/day and metformin extended-release 2,000 mg/day. Concomitant strong CYP3A4/5 inhibitors: maximum saxagliptin 2.5 mg/day.

Children: Not recommended.

Contraindications: Renal impairment (serum creat­inine ≥1.5 mg/dL [men], ≥1.4 mg/dL [women]). Metabolic acidosis, diabetic ketoacidosis. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use).

Warnings/Precautions: Not for treating type 1 diabetes. Confirm normal renal function before starting; monitor (especially in patients aged 80 years and older). Avoid in hepatic disease. Discontinue if lactic acidosis, shock, acute MI, sepsis, or hypoxemia occurs. Suspend therapy if dehydration occurs or before surgery. Monitor hepatic function, hematology (especially serum vitamin B12 in susceptible patients). Elderly, debili­tated, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Pregnancy (Category B), nursing mothers: not recommended; consider using insulin instead.

Interactions: Saxagliptin potentiated by strong CYP3A4/5 inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Cationic drugs eliminated by renal tubular secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, triamterene, trimethoprim, ranitidine, vancomycin): may increase metformin levels. Avoid excessive alcohol intake (potentiates effects of metformin on lactate). Diuretics, steroids, phenothiazines, phenytoin, sympathomimetics, calcium channel blockers, isoniazid, niacin, others may cause hyperglycemia. Increased risk of hypoglycemia with alcohol, sulfonylureas. beta-blockers may mask hypoglycemia.

Adverse reactions: GI upset, upper respiratory infection, urinary tract infection, headache, nasopharyngitis, hypersensitivity reactions; lactic acidosis.

How supplied:

Tabs 5/500—30

5/1000—30, 90, 500

2.5/1000—60, 500

For more information, call 800.721.5072 or visit