By Lilian Anekwe
A new class of drug to treat type 2 diabetes, which reduces the reabsorption of glucose in the kidneys, have been shown to be safe and effective in a phase III trial led by UK researchers.
Dapagliflozin, a selective sodium-dependent glucose transporter inhibitor, produced greater reduction in HbA1c and weight loss, with no apparent effect on the reported rate of hypoglycaemia, researchers said.
The drug, manufactured by Bristol-Myers Squibb and AstraZeneca, suppresses the activity of a protein called SGLT2, which is responsible for the majority of glucose reabsorption in the kidney.
Suppressing the activity of this protein inhibits the renal-glucose reabsorption in patients with type 2 diabetes, leading to more excretion of glucose in the urine and better regulation of blood glucose levels.
A randomised controlled trial of 534 adults with type 2 diabetes, who were receiving high doses of daily metformin of at least 1,500mg a day but who still had inadequate glycaemic control, were randomised to additionally receive one of three doses of dapagliflozin – 2.5, 5 or 10mg.
After 24 weeks their change in HbA1c from baseline was measured and compared with controls also on metformin but given only placebo in addition.
After six months, mean HbA1c had decreased by 0.3% in the placebo group, compared with 0.67% in those one the 2.5mg dose of dapagliflozin, 0.7% in those on the 5mg dose and 0.84% in those on the 10mg dose.
Weight loss was also greater in patients given the new drug. Patients on the 2.5mg dose lost an average of 2.21kg, those on the 5mg dose lost 3.04 kg, and those on the 10mg dose lost 2.86kg. By comparison patients in the placebo group lost 0.89kg.
Significantly more patients given the new drug reached an HbA1c target of 7% or lower – 41% in the 10mg group, 38% in the 5mg group, 33% in the 2.5mg group but 26% in the placebo group.
Researchers at the American Diabetes Association told delegates that there was no apparent risk of hypoglycaemia, which occurred in 3% of patients on placebo and between 2 and 4% of controls.
The incidence of urinary tract infections and other adverse events were the same, but there was a higher reported rate of genital infections, including candida, in patients given dapagliflozin.
Professor Cliff Bailey, professor of clinical science at Aston University, led the research, published online by The Lancet to coincide with its presentation at the American Diabetes Association conference in Orlando, and concluded: ‘Addition of dapagliflozin to metformin provides a new therapeutic option for treatment of type 2 diabetes in patients who have inadequate control with metformin alone.’
He told delegates: ‘Patients on this drug show a dose-related reduction in blood glucose. This brought a much larger proportion of patients to their blood glucose targets.
‘Now we have evidence that the kidney provides us with a mechanism that is not one dependent for the removal of excess glucose in the urine, and which can be used as an add-on to metformin treated type 2 diabetes.’
A second trial led by researchers at the University of Liverpool also found similar results, with a statistically significant mean reduction in HbA1c from baseline of 0.75%, 0.82% and 0.9% in patients on insulin and the 2.5, 5 and 10mg dose of dapagliflozin respectively compared to placebo.
Weight loss was greater in the dapagliflozin group, who also showed a reduction in daily insulin dose of 1.8IU/d for dapagliflozin 2.5mg, 0.61IU/d for dapagliflozin 5mg and 1.16 for dapagliflozin 10mg.
Professor John Wilding, professor of medicine at the University Hospital in Aintree said the results ‘suggested that further study of dapagliflozin in this patients population is warranted.’
The Lancet, published online June 26 and American Diabetes Association abstract no 78-OR
Hope for new class of diabetes drug