FDA Approves Xigduo XR for Type 2 Diabetes

The FDA has approved once-daily Xigduo XR, a novel combination of dapagliflozin and metformin hydrochloride extended-release, to treat type 2 diabetes, according to a press release.

The drug is the first to combine the sodium glucose cotransporter-2 inhibitor dapagliflozin, marketed as Farxiga in the United States, with the biguanide metformin hydrochloride extended-release (XR).

Xigduo XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with dapagliflozin and metformin is appropriate.

The drug, however, is not recommended for patients with type 1 diabetes or diabetic ketoacidosis. Its label also contains a boxed warning for lactic acidosis, which can occur due to metformin accumulation during treatment.

Further, the novel combination is contraindicated in those with moderate to severe renal impairment; a history of serious hypersensitivity to dapagliflozin or metformin; or with metabolic acidosis, including diabetic ketoacidosis.

The agency based its decision for approval on four phase 3 clinical trials that demonstrated the safety and efficacy of dapagliflozin and metformin IR or XR tablets in treatment-naïve patients and in patients inadequately controlled with metformin. Researchers also compared the combination’s performance with glipizide plus metformin.

No clinical studies have been conducted with Xigduo XR combination tablets, but bioequivalence was demonstrated in healthy adults between Xigduo XR and dapagliflozin plus metformin XR as separate tablets, according to the release.

Currently, Xigduo XR is approved with multiple dosage strengths of dapagliflozin and metformin extended-release, including 5 mg/500 mg, 5 mg/1,000 mg, 10 mg/500 mg and 10 mg/1,000 mg. The starting dose should be based on each individual patient’s current treatment regimen.

The release also states that Xigduo XR should be taken once daily in the morning with food with gradual dose escalation to reduce the risk for gastrointestinal side effects related to metformin. The maximum daily recommended dose is 10 mg for dapagliflozin and 2,000 mg for metformin.