FDA approves Farxiga to treat type 2 diabetes; bladder cancer concerns remain

FDA has approved dapagliflozin tablets (Farxiga, Bristol-Myers Squibb and AstraZeneca) to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes. This marks a rebound for the drug, which FDA rejected last year, citing concerns raised by studies linking the drug to bladder cancer and liver toxicity.

“Farxiga is a once-a-day tablet that offers an additional therapeutic option on the market for individuals with diabetes. Compared to other oral diabetes drugs, it has a novel mechanism of action that provides a different treatment approach for people with type 2 diabetes,” said Abimbola Farinde, PharmD, MS, who serves on the faculty at Columbia Southern University, Orange Beach, Ala.

Farxiga is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. The drug’s safety and effectiveness were evaluated in 16 clinical trials involving more than 9,400 patients with type 2 diabetes. The trials showed improvement in HbA1c (hemoglobin A1c or glycosylated hemoglobin, a measure of blood sugar control). 

Farxiga has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, pioglitazone, glimepiride, sitagliptin, and insulin. It should not be used to treat patients with type 1 diabetes, patients who have increased ketones in their blood or urine (diabetic ketoacidosis), or patients with moderate or severe renal impairment or end-stage renal disease. Patients on dialysis should not be treated with Farxiga.
 
An increased number of bladder cancers was identified among Farxiga users in clinical trials, so Farxiga is not recommended for patients with active bladder cancer. Patients with a history of bladder cancer should talk to their physician before using Farxiga. Farxiga can cause dehydration, leading to a drop in blood pressure that can result in dizziness and/or fainting, and a decline in renal function. The elderly, patients with impaired renal function, and patients taking diuretics for treatment of other conditions appeared to be more susceptible to this risk.

FDA is requiring six post-marketing studies for Farxiga:

• A cardiovascular outcomes trial (CVOT) to evaluate the cardiovascular risk of Farxiga in patients with high baseline risk of cardiovascular disease;

• A double-blind, randomized, controlled assessment of bladder cancer risk in patients enrolled in the CVOT;

• An animal study evaluating the role of Farxiga-induced urinary flow/rate and composition changes on bladder tumor promotion in rodents;

• Two clinical trials to assess the pharmacokinetics, efficacy, and safety in pediatric patients;

• An enhanced pharmacovigilance program to monitor reports of liver abnormalities and pregnancy outcomes.

The most common side effects observed in clinical trials in patients treated with Farxiga were genital mycotic (fungal) infections and urinary tract infections.

 Type 2 diabetes affects about 24 million people and accounts for more than 90% of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.