Indication(s):

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 and postprandial glucose levels in a glucose-dependent manner. Metformin improves ­glucose tolerance in type 2 diabetes by decreasing hepatic glucose production, decreased 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. The coadministration of saxagliptin 5mg/day plus metformin resulted in significant improvements in A1C, fasting plasma ­glucose, and 2-hour postprandial glucose compared to placebo plus metformin.

In another study, saxagliptin 2.5mg and 5mg was given as add-on therapy to patients with inadequate glycemic control on metformin immediate-release alone. This combination provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to metformin immediate-release.

Legal Classification:

Rx

Adults:

Take once daily with evening meal. Swallow whole. Individualize; titrate based on response. Maximum saxagliptin 5mg/day and metformin extended-release 2000mg/day. Concomitant strong CYP3A4/5 ­inhibitors: maximum saxagliptin 2.5mg/day.

Children:

Not recommended.

Contraindication(s):

Renal impairment (serum creatinine ≥1.5mg/dL [men], ≥1.4mg/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 (esp. in patients ≥80yrs). 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 (Cat.B), nursing mothers: not recommended; consider using insulin instead.

Interaction(s):

Saxagliptin potentiated by strong CYP3A4/5 inhibitors (eg, ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Cationic drugs eliminated by renal tubular secretion (eg, 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. ß-blockers may mask hypoglycemia.

Adverse Reaction(s):

GI upset, URI, UTI, headache, nasopharyngitis, hypersensitivity reactions; lactic acidosis (rare, half the cases are fatal).

How Supplied:

Tabs 5/500—30
5/1000—30, 90, 500
2.5/1000—60, 500

Last Updated:

1/28/2011