XIGDUO XR is a combination of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and metformin, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both dapagliflozin and metformin is appropriate. (1)

Limitation of use:

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Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. (1.1)

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Individualize the starting dose based on the patient’s current treatment. (2.1)

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Administer once daily in the morning with food. (2.1)

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Swallow whole. Never crush, cut, or chew. (2.1)

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Do not exceed a daily dose of 10 mg dapagliflozin/2000 mg metformin HCl extended-release. (2.1)

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No dosage adjustment is indicated in patients with mild renal impairment. (2.2)

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XIGDUO XR should not be used in patients with moderate to severe renal impairment (defined as eGFR <60 mL/min/1.73 m 2 or CrCl <60 mL/min) or end-stage renal disease. ( 2.2, 4, 5.3)

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5 mg dapagliflozin/500 mg metformin HCl extended-release (3)

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5 mg dapagliflozin/1000 mg metformin HCl extended-release (3)

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10 mg dapagliflozin/500 mg metformin HCl extended-release (3)

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10 mg dapagliflozin/1000 mg metformin HCl extended-release (3)

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Moderate to severe renal impairment. ( 4, 5.3)

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History of serious hypersensitivity to dapagliflozin or hypersensitivity to metformin hydrochloride. ( 4, 6.1)

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Metabolic acidosis, including diabetic ketoacidosis. ( 4, 5.1)

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Lactic acidosis: Warn patients against excessive alcohol intake. XIGDUO XR should generally be avoided in hepatic impairment and contraindicated in moderate to severe renal impairment. Ensure normal or mildly impaired renal function before initiating and at least annually thereafter. Temporarily discontinue XIGDUO XR in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. ( 2.2, 4, 5.1, 5.2, 5.3, 5.5, 5.6, 5.7, 5.8, 5.10, 5.11, 8.5, 8.6)

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Hypotension: Before initiating XIGDUO XR, assess volume status and correct hypovolemia in the elderly, in patients with renal impairment or low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy. ( 5.4, 6.1)

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Hypoglycemia: In patients taking insulin or an insulin secretagogue with XIGDUO XR, consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia. (5.9)

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Vitamin B12 deficiency: Metformin may lower vitamin B 12 levels. Measure hematological parameters annually. ( 5.12, 6.1)

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Genital mycotic infections: Monitor and treat if indicated. (5.13)

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Increased LDL-C: Monitor and treat per standard of care. (5.14)

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Bladder Cancer: An imbalance in bladder cancers was observed in clinical trials. Dapagliflozin should not be used in patients with active bladder cancer and should be used with caution in patients with a prior history of bladder cancer. (5.15)

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Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with XIGDUO XR or any other antidiabetic drug. (5.16)

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The most common adverse reactions associated with XIGDUO XR (5% or greater incidence) were female genital mycotic infection, nasopharyngitis, urinary tract infection, diarrhea, and headache. (6.1)

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Adverse reactions reported in >5% of patients treated with metformin extended-release and more commonly than in patients treated with placebo are: diarrhea and nausea/vomiting. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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Cationic drugs: eliminated by renal tubular secretion may reduce metformin elimination; use with caution. ( 5.10, 7.3)

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Pregnancy: There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. (8.1)

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Nursing Mothers: Discontinue XIGDUO XR or discontinue nursing. (8.3)

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Geriatrics: Higher incidence of adverse reactions related to reduced intravascular volume. ( 5.4, 8.6)

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Renal Impairment: Higher incidence of adverse reactions related to reduced intravascular volume and renal function. ( 5.3, 6.1)