A once-daily, extended-release formulation that combines dapagliflozin and metformin (Xigduo XR) has been approved for the treatment of type 2 diabetes in adults, announced manufacturer AstraZeneca.

 

The two medications have complementary modes of action, the company explained in a press release. Metformin is a biguanide, while dapagliflozin (Farxiga) is an SGLT2 inhibitor that removes glucose via the kidney for excretion.

 

"The kidney plays a contributing role in maintaining normal glucose balance, in part by filtering and subsequently reabsorbing glucose back into circulation. SGLT2, a sodium-glucose co-transporter found predominantly in the kidney, is responsible for the majority of glucose reabsorption," the company said.

 

The new formulation is intended to be used as an adjunct to diet and exercise for patients considered suitable candidates for treatment with both medications.

 

It will be available in several dosage strengths of dapagliflozin and metformin, including 5 mg/500 mg, 5 mg/1,000 mg, 10 mg/500 mg, and 10 mg/1,000 mg. The dose should be individualized according to the patient's current regimen, beginning with low doses to minimize the likelihood of adverse gastrointestinal events.

 

The maximum recommended dose is 10 mg/2,000 mg per day.

 

The approval is based on demonstrated bioequivalence for the SGLT2 inhibitor plus metformin XR when given as separate medications. Treatment with dapagliflozin plus metformin was evaluated in four phase III studies that showed the combination was safe and effective in patients who were treatment naive, in those whose glucose was inadequately controlled with metformin alone, and in comparison with glipizide plus metformin.

 

The extended-release combination is already approved for use in Australia, while dapagliflozin plus immediate-release metformin is currently available in the European Union.

 

Xigduo XR is contraindicated in patients with moderate-to-severe renal impairment, a history of serious hypersensitivity, and in acute or chronic metabolic acidosis.

 

Lactic acidosis, which can occur with the accumulation of metformin, has been reported in 0.03 cases per 1,000 patient-years, and has been fatal in half. The risk of lactic acidosis is increased in patients with conditions such as hepatic and renal impairment, dehydration, and congestive heart failure.

 

Other side effects include a risk of urinary tract infections, owing to the increased sugar content in urine that results from SGLT2 inhibition.

 

By Nancy Walsh, 

Senior Staff Writer, MedPage Today