Dapagliflozin Trial Stirs Controversy

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A new trial with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin (brand name Farxiga) is recruiting COVID-19 patients with type 2 diabetes and other conditions to assess whether the drug can reduce COVID-19 progression.

However, the 900-patient, placebo-controlled DARE-19 trial (Dapagliflozin in Respiratory Failure in Patients with COVID-19) with the drug is proving controversial.

The AstraZeneca (Cambridge, UK) trial of dapagliflozin calls for COVID-19 patients with a history that includes at least one of these conditions: type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, heart failure and/or chronic kidney disease stage 3 to 4 (eGFR ≥25 mL/min/1.73 m2).

During the pandemic, many physicians are avoiding the use of dapagliflozin in diabetic patients with the new virus because of an increased risk of diabetic ketoacidosis. The trial aims to determine feasibility of the drug as a treatment option for COVID-19 patients at risk for developing complications like organ failure.

Recently, an international group of diabetes experts published an article in The Lancet: Diabetes and Endocrinology that recommended the following precaution: “Regarding medications, the panel advises that both metformin and sodium-glucose cotransporter 2 inhibitors be stopped in patients with COVID-19 and type 2 diabetes to reduce the risk of acute metabolic decompensation.” Likewise, Diabetes UK has issued this guidance: “If you have type 2 diabetes and you take SGLT2i tablets, you can keep taking these unless you become unwell. If you are unwell, these tablets could increase your risk of developing diabetic ketoacidosis.”

Two other makers of SGLT2i drugs have commented on whether they plan trials with their drugs, the New York Times reported. Johnson & Johnson (New Brunswick, NJ) has no plans for a COVID-19 trial with its drug, Invokana (canagliflozin), which slows the progression of kidney failure, the paper reported.

Boehringer Ingelheim and Eli Lilly (Ingelheim am Rein, Germany, and Indianapolis, IN), makers of Jardiance (empagliflozin), which helps improve blood sugar control and cardiovascular risk in type 2 diabetes, stated that they are “carefully assessing” products as potential COVID-19 treatments. The companies note, however, that Jardiance users who have acute illness have a greater ketoacidosis risk.

In answer to those challenging the trial, AstraZeneca has stressed that type 1 diabetic patients with COVID-19 will not be enrolled in the trial and that participating patients will be closely monitored for safety by an independent data monitoring committee. Results of the trial are expected in December 2020.