June 26th, 2010
A new drug for type 2 diabetes—dapagliflozin—acts independently of insulin, improves blood sugar control, and lowers bodyweight.
The drug could thus be considered as a new therapeutic option for diabetes patients who have inadequate blood sugar control with the first line drug metformin, and also for early-stage and late-stage diabetes. The findings are reported in this week’s American Diabetes Association meeting Special Issue of The Lancet, written by Professor Clifford Bailey, Aston University, Birmingham, UK, and colleagues.
Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. The drug works by preventing reabsorption of glucose in the kidneys, and promoting excretion of glucose in the urine. Thus the drug reduces high levels of blood glucose (hyperglycaemia) without affecting insulin-dependent systems. Since many complications of diabetes are related to high concentrations of blood glucose, directly lowering blood glucose is a legitimate target for new drugs for diabetes. In this study, the authors assessed the efficacy and safety of dapagliflozin in patients not managing to control their blood sugar with the first-line treatment of metformin.
This phase 3 randomised controlled trial assessed 546 adult patients with diabetes, who were receiving daily metformin, yet had inadequate blood sugar control. Patients were randomly assigned to one of three doses of dapagliflozin or placebo orally once daily (2.5mg 137 patients, 5mg 137 patients, 10mg 135 patients, placebo 137 patients). All patients continued to receive metformin at their pre-study doses. The primary outcome was improvement in blood sugar control measured by haemoglobin A1c (HbA1c)* levels at 24 weeks.
A total of 534 patients were included in the final analysis (dapagliflozin 2.5mg 135 patients; 5mg 133; 10mg 132; placebo 134). Mean HbA1c decreased by 0.3% in the placebo group, compared with 0.67% in the 2.5mg group, 0.70% in the 5mg group and 0.84% in the 10mg group. Hypoglycaemia (abnormally low blood sugar) was reported at similar frequency in both groups. Symptoms of genital infections were more common in the dapagliflozin groups (between 8% and 13%) compared with placebo (5%). This is likely to reflect the extra glucose that is eliminated in the urine. Serious adverse events were rare and occurred at similar rates in all four groups.
Mean bodyweight loss was 0.9kg per person in the placebo group, compared with 2.2kg in the dapagliflozin 2.5mg group, 3.0kg in the 5mg group, and 2.9kg in the 10mg group. Although bodyweight loss would be expected due to the mechanism of action of dapagliflozin (a mild diuretic effect meaning loss of fluid from the body), continuing weight reduction plus reduced waist circumference over the study suggested patients were losing fat as well as water.
The authors conclude: “This trial shows that dapagliflozin can improve blood glucose control in patients who have inadequate control with metformin. The drug acts independently of insulin, lowers weight, and is not associated with risk of hypoglycaemia. Safety and tolerability of the drug were also confirmed. Therefore, addition of dapagliflozin to metformin provides a new therapeutic option for treatment of type 2 diabetes.”
In an accompanying comment, Dr Markolf Hanefeld, Centre for Clinical Studies, Dresden, Germany, and Dr Thomas Forst, The Institute for Clinical Research and Development (IKFE), Mainz, Germany, say: “The net balance of this novel group of oral antidiabetic drugs looks promising…because of the role of glucotoxicity in the pathophysiology of type 2 diabetes, and in view of weight loss and low risk of hypoglycaemia, SGLT2 inhibitors in the future might also be considered for treatment of early-stage and late-stage type 2 diabetes.”
Professor Bailey is attending the ADA meeting, and will be travelling or in USA from Thurs June 24. For interviews, please arrange via Sally Finn T) +44 (0) 121 204 4552 E) firstname.lastname@example.org and Alex Earnshaw T) +44 (0) 121 204 4549 E) email@example.com / firstname.lastname@example.org
Dr Markolf Hanefeld, Centre for Clinical Studies, Dresden, Germany. T) +49 351 4400580 /+49 351 4400582 E)email@example.com
For full article and comment see:http://press.thelancet.com/adadapag.pdf
Note to editors: *HbA1c is used to indicate the average plasma glucose concentration of the preceding two to three months. In general, the reference range (that found in healthy persons who do not have diabetes), is about 4%—5.9%. Patients with diabetes usually have HbA1c levels above 6.5%.