New sodium-glucose transporter-2 inhibitor effective in type 2 diabetes

NEW YORK (Reuters) - 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 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. 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.

The 800 patients in the 24-week 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 mg, 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 hemoglobin (Hb)A1C were seen at all dapagliflozin doses, researchers said. Patients began the study with A1C levels between 7.5% and 10.5%. ADA guidelines call for getting A1C levels down to 7 percent or lower.

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

Dapagliflozin also led to weight loss: an average of 0.98 kg (2.2 lb) after 24 weeks on the two lower doses and 1.67 kg (3.7 lb) at 10 mg. The placebo group averaged very slight 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.

The incidence of serious hypoglycemia 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% in each group, Dr. 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," Dr. Wilding said.

Nyhetsinfo
www red DiabetologNytt