FDA Approves Xigduo XRThursday, November 20, 2014
With the approval of this medicine to the U.S. market, Xigduo XR is the first product that combines two agents with complementary mechanisms of action, dapagliflozin (trade name in the US, FARXIGA), an inhibitor of sodium-glucose cotransporter 2 (SGLT2), and metformin hydrochloride (HCl) extended-release, a biguanide, in a once-daily oral tablet.
Xigduo XR should be taken once daily in the morning with food with gradual dose escalation to reduce the risk of gastrointestinal (GI) side effects due to metformin. The maximum daily recommended dose is 10 mg for dapagliflozin and 2,000 mg for metformin HCl. Xigduo is approved with multiple dosage strengths of dapagliflozin and metformin HCl extended release, respectively, including 5 mg/500 mg, 5 mg/1000 mg, 10 mg/500 mg, and 10 mg/1000 mg, and the starting dose should be individualized based on each patient’s current treatment regimen.
This combination medication product is already approved in Australia for the treatment of adults with type 2 diabetes, along with diet and exercise. Xigduo (dapagliflozin and metformin hydrochloride), which uses an immediate-release form of metformin, is approved in the European Union.
The FDA's approval of the combination was based on four phase 3 clinical trials demonstrating efficacy and safety of the separate dapagliflozin and metformin intermediate-release or XR tablets in treatment-naive patients and those inadequately controlled on metformin, as well as when compared with the combination of a sulfonylurea plus metformin.
Dapagliflozin in combination with metformin was evaluated in different studies involving 3,200 adults with type 2 diabetes.
The combination medication products have shown:
- Hemoglobin A1c (HbA1c) decreased by 0.65% from baseline after 16 weeks Vs. 0.3% reduction with placebo group; and
- Weight reduction of 2 kg from baseline more than placebo plus metformin group
Other studies that involved dapagliflozin taken with metformin and another diabetes medicine, sitagliptin or insulin, for 24 weeks have reported:
- HbA1c decreased by 0.40% from baseline more than placebo and metformin when added to sitagliptin;
- HbA1c decrease by 0.61% from baseline more than placebo and metformin when added to insulin; and
- Average reduction in body weight of around 2 kg from baseline more than those taking placebo plus metformin.
The most common side effects with Xigduo (which may affect more than 1 in 10 people) are hypoglycemia (when used together with insulin or a sulfonylurea, and Gastrointestinal symptoms.
Xigduo is contraindicated in patients with reduced liver function and renal dysfunction. For the full list of restrictions, see the package insert.
The approval of once-daily Xigduo XR provides prescribers and adult patients with another treatment choice, supporting a more personalized approach to disease management. The combination adds a significant benefit to the current treatment by combining a SGLT2 inhibitor, which reduces the reabsorption of glucose and enables its removal via the urine and metformin which inhibits glucose production and reduces its absorption in the gut.
I believe that with the increase number of medications for diabetes, it is important to consider medication compliance and ease of medication administration. Using a combination medication product that introduces 2 unique mechanism and is taken in 1 medication form once daily can significantly impact compliance of patients with the medication regimen and help to provide better glycemic control.