First Details of Empagliflozin Trials Follow US and EU Filings

PHOENIX — An investigational sodium glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin (Boehringer Ingelheim), lowered glucose to a similar degree as metformin and also produced sustained weight loss for up to 90 weeks in an open-label extension study in patients with type 2 diabetes.

The data were presented during a late-breaking clinical-trial session on May 5 at the American Association of Clinical Endocrinologists (AACE) 2013 Scientific & Clinical Congress by Thomas Hach, MD, senior medical director, Boehringer Ingelheim, Germany.

Empagliflozin is one of a new class of glucose-lowering drugs, the oral SGLT2 inhibitors, which produce increased urinary glucose excretion, with a consequent lowering of plasma glucose levels, as well as weight loss.

Canagliflozin was the first of these agents to be approved in the US at the end of March; another, dapagliflozin, was rejected by the Food and Drug Administration (FDA) but is approved for marketing in Europe.

A new drug application (NDA) has been submitted to the US FDA for empagliflozin, and a decision is expected in the first quarter of 2014, Dr. Hach told Medscape Medical News. An application for marketing in the European Union has also been filed.

"Most important, clinicians should understand that glucose in the urine isn't bad. We were all trained in medical school that glucose in the urine is bad and is a sign of diabetes… But in fact, it actually makes sense," he noted.

Indeed, Alan Garber, MD, president of AACE and professor of medicine, biochemistry, molecular biology, and molecular and cellular biology at Baylor College of Medicine, Houston, Texas, said of the SGLT2 inhibitors in general, "They're very effective drugs. The only question really is the adverse-event profile and the eligible patient population." For example, certain patients with impaired renal function may not be good candidates, he told Medscape Medical News.

As for how empagliflozin might stack up against canagliflozin with regard to safety and efficacy, "I think they're substantially very similar. Until you get head-to-head trials, no one will really know," said Dr. Garber.

Empagliflozin as Monotherapy and Add-On to Metformin

Dr. Hach presented data from a randomized, 78-week extension study that followed 2 separate 12-week randomized controlled trials. In 1 trial, patients were randomized to 10-mg or 25-mg empagliflozin or to metformin, as monotherapy, in 81, 82, and 80 patients, respectively. The second study randomized 71, 70, and 71 patients, respectively, to empagliflozin 10 mg or 25 mg or to sitagliptin as an add-on to metformin.

The patients had a mean age of about 50 years, mean baseline body mass index of about 30 kg/m² and glycated hemoglobin (HbA_1c) of approximately 8%. Individuals with estimated glomerular filtration (eGFR) rates below 60 mL/min/1.73 m² were excluded.

At 90 weeks, adjusted mean percentage-point reductions from baseline in HbA_1c were 0.51 for empagliflozin 10 mg and 0.60 for 25 mg, compared with 0.64 for metformin as monotherapy.

When added to metformin as background, percentage-point reductions were 0.61 for empagliflozin 10 mg and 0.74 for 25 mg vs just 0.45 with sitagliptin.

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Graham
Let me get this straight Graham. A drug no doubt costing far more than Metformin with possible unknown side effects and at 90 weeks, adjusted mean percentage-point reductions from baseline in HbA1c were 0.51 for empagliflozin 10 mg and 0.60 for 25 mg, compared with 0.64 for metformin as monotherapy. So, not as effective as Metformin which is a cheap and safe drug. And a minuscule improvement when used with Metformin. You have to marvel how big pharma trots this dross out, I’ll be giving it a miss. I reckon about half a hobnob biscuit would negate any benefit in BG control.

Eddie