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FDA approves new oral combination treatment for type 2 diabetes

A new treatment option is now available in the United States for adults with type 2 diabetes mellitus (T2DM). In 2014, AstraZeneca released a statement announcing that the US Food and Drug Administration (FDA) has approved Xigduo XR, a once-daily oral tablet containing two active substances: dapagliflozin and metformin hydrochloride extended-release.1 In conjunction with diet and exercise, Xigduo XR delivers a combination of anti-hyperglycemic mechanisms to help T2DM patients control their blood glucose levels.

Dapagliflozin, marketed by AstraZeneca under the trade name Farxiga, is part of a relatively new class of drugs for T2DM called sodium-glucose co-transporter 2 (SGLT2) inhibitors. It decreases blood glucose levels by blocking SGLT2 proteins in the kidneys from performing their usual function of transferring glucose from urine into the bloodstream, allowing more glucose to be eliminated from the body via urine. Metformin hydrochloride, a long-standing first-line agent for treating T2DM, works by suppressing glucose production in the liver and preventing glucose from being reabsorbed by the intestines. It also helps muscle cells to process glucose more efficiently. Xigduo XR features an extended-release formulation of metformin that allows for a single daily dose.

Because it is available in four different combined dosage strengths, Xigduo XR may offer patients and their physicians the opportunity for more flexible and personalized treatment regimens. It is indicated for adults with T2DM who are eligible for treatment with both dapagliflozin and metformin. To avoid potential gastrointestinal side effects of metformin, Xigduo XR should be taken with food and its dosage should be increased gradually. It is not appropriate for patients with type 1 diabetes mellitus and it has not yet been adequately studied in T2DM patients under 18 years of age or in women who are pregnant or breastfeeding.

Xigduo XR contains a boxed warning about the risk of lactic acidosis, a rare but extremely serious condition that can affect patients taking metformin. Because of the way Xigduo XR functions in the kidneys, renal function should be assessed both before and during treatment. For this reason, it is not a recommended treatment for patients with existing moderate to severe renal impairment or metabolic acidosis. Patients should also be monitored regularly for hypotension (low blood pressure) and hypoglycemia.

The FDA approved Xigduo XR after four Phase III clinical trials established that the combination of dapagliflozin plus metformin was effective and safe for T2DM patients who had received no prior treatment, as well as patients whose blood glucose was not adequately controlled by metformin treatment alone. The combination also had equivalent efficacy and safety profiles when compared to treatment with glipizide (a sulfonylurea) plus metformin, another dual-action treatment for managing T2DM. This means that Xigduo XR is an alternative option for a combination therapy with metformin for patients who cannot tolerate sulfonylureas. The most common adverse effects reported by 5% or more of participants in the clinical trials include female genital mycotic infection (yeast infection), nasopharyngitis, urinary tract infection, diarrhea, nausea, and headache.

Xigduo XR has already been authorized for patients with T2DM in Australia since July 2014. In January 2014, the European Medicines Agency approved a slightly different version that contains immediate-release rather than extended-release metformin. This avenue of research and development for the treatment of T2DM is part of an industry-wide trend, with several of the major pharmaceutical companies developing and testing similar SGLT2 inhibitors.2 Both Johnson & Johnson and Boehringer Ingelheim have had SGLT2 inhibitors (canagliflozin and empagliflozin, respectively) earn FDA approval this year and Pfizer has its own currently in the pipeline (ertugliflozin). Although there is one other combination of SGLT2 inhibitor plus metformin currently on the US market, Johnson & Johnson’s Invokamet (canagliflozin plus metformin), Xigduo XR is the first to receive a green light from the FDA for a combination with an extended release formulation of metformin that makes it possible for patients to take just one dose a day.

  1. AstraZeneca [press release]. US FDA approves once-daily XIGDUO™ XR tablets for adults with type 2 diabetes. October 30, 2014. Available at: Accessed October 31, 2014.
  2. Garde D. AstraZeneca wins another diabetes approval in a fast-crowding market. FierceBiotech. October 30, 2014. Available at: Accessed October 31, 2014.