New diabetes drug effective in study

An experimental drug from a promising new class of medicines significantly reduced blood sugar in patients with advanced type 2 diabetes in a late-stage clinical trial.

The drug, dapagliflozin, also led to statistically significant weight loss and a slight reduction in needed insulin dose, according to data presented at the American Diabetes Association scientific meeting in Orlando on Saturday.

Dapagliflozin is being developed by Bristol-Myers Squibb Co and AstraZeneca PLC. It belongs to a new class of oral type 2 diabetes treatments called sodium-glucose transporter-2 inhibitors. Blocking the “SGLT2” protein significantly increases the amount of glucose excreted in the urine that would otherwise be reabsorbed into the blood after passing through the kidneys.

“The most interesting thing here is that this drug, because of this mode of action, can in theory be used right at the very beginning of the disease or it can be used, as we’ve shown in this study, really quite late on in patients who are struggling to control their diabetes on insulin, with or without other oral agents,” Dr John Wilding, the study’s lead investigator who presented the data, said in a telephone interview.

Earlier successful Phase III studies tested dapagliflozin alone and in combination with metformin, which is typically one of the first medicines doctors turn to in treating type 2 diabetes.

The study presented on Saturday tested the drug in patients whose disease had progressed to the point where they required insulin and still were not reaching ADA blood sugar targets.

While insulin use is generally associated with type 1 diabetes, about 20 percent to 30 percent of the type 2 diabetes population requires insulin as the disease progresses, Wilding said. Patients in the 24-week, 800-patient study on average had suffered from diabetes for 13.6 years and had been on insulin for an average of six years.

Patients received dapagliflozin once a day at doses of 2.5 milligrams, 5 mg, 10 mg or a placebo. They all continued to take insulin, and some were also on other oral treatments.

Highly statistically significant reductions in levels of A1C, a commonly used blood sugar measure, were seen at all dapagliflozin doses, researchers said. Patients began the study with A1C levels between 7.5 percent and 10.5 percent. ADA guidelines call for getting A1C levels down to 7 percent or lower.

A1C was reduced by 0.75 percent at the lowest dose of dapagliflozin, by 0.82 percent at 5 mg and by 0.9 percent at the highest dose, compared with a reduction of 0.3 percent in the placebo group.

Dapagliflozin also led to weight loss as calories are excreted in the urine along with blood glucose. The average weight loss was 0.98 kg (2.2 pounds) after 24 weeks on the two lower doses and 1.67 kg (3.7 pounds) at 10 mg, while the placebo group averaged very slight weight gain.

Weight loss is an especially attractive effect in diabetes treatments as obesity is a leading cause of type 2 diabetes and some older medicines cause weight gain.

Dapagliflozin also led to a statistically significant reduction in daily insulin dose at 24 weeks at all three tested doses, compared with an increase in the placebo group.

Incidence of serious hypoglycemia, or dangerously low blood sugar, was low and distributed across all arms of the study, including the placebo group, leading researchers to believe they were insulin related and not caused by dapagliflozin.

There was a higher incidence of symptoms and signs of urinary tract infection associated with dapagliflozin that had been seen in earlier studies as well as in trials of other drugs in the same class. But the number of patients discontinuing treatment due to the condition was very small, about 1 percent in each group, Wilding said.

He said dapagliflozin also generally led to a small reduction in blood pressure, another beneficial side effect.

“The trial data that we have so far is supportive that this drug will have a place in the treatment of diabetes,” Wilding said.

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By Bill Berkrot

NEW YORK (Reuters)