New Diabetes Drug Dapagliflozin Closer to Approval
Dapagliflozin, a new drug for treatment of type 2 diabetes, met its goals in Phase III clinical trials, according to a release issued by the pharmaceutical company AstraZeneca. The investigational drug is a joint venture of AstraZeneca and Bristol-Myers Squibb Company, who plan to file for approval of dapagliflozin with the Food and Drug Administration (FDA) in late 2010 or early 2011.
Dapagliflozin is a potential first entry into the class of sodium glucose co-transporter 2 (SGLT2) inhibitors. The protein SGLT2 helps the body retain glucose for energy, but in people with diabetes, retention of excess glucose leads to hyperglycemia (high glucose levels). A SGLT2 inhibitor works by facilitating the elimination of glucose by the kidneys, which helps return serum glucose levels toward normal levels. This is critical, as high, uncontrolled glucose levels can cause or contribute to serious diabetes complications, including eye problems (including blindness), kidney damage, nerve damage (neuropathy), gum disease, foot problems, heart disease, and stroke.
Results of a 24-week Phase III clinical trial showed that dapagliflozin, when taken along with metformin by people with type 2 diabetes, significantly reduced glycosylated hemoglobin (HbA1c) levels . Glycated hemoglobin is a substance in red blood cells that is formed when blood sugar attaches to hemoglobin. The HbA1c level is a good indicator of how well diabetes is being managed. Trial results also showed that the combination of dapagliflozin and metformin successfully controlled fasting plasma glucose levels in patients who were unable to achieve this goal on metformin alone.
Participants in the 24-week Phase III clinical trial included 546 individuals with type 2 diabetes whose disease was not controlled adequately with their current treatment. Specifically, they had HbA1c levels between 7.0 and 10.0 percent: normal range is 4.0 to 5.9 percent, while 8.0 percent or higher is considered poorly controlled diabetes and less than 7.0 percent is considered well controlled. The patients were randomly assigned to one of four treatment groups: either 2.5 mg, 5 me, or 10 mg dapagliflozin, or placebo. Patients in all the groups also received at least 1,500 mg metformin daily.
After 24 weeks, patients who received any of the three doses of dapagliflozin plus metformin had a statistically significant improvement in HbA1c and in fasting plasma glucose levels when compared with the placebo group. The percentage of patients who achieved HbA1c of less than 7 percent at the end of the study was 33.0 percent in the 2.5 mg dapagliflozin group, 37.5 percent in the 5 mg group, and 40.6 percent in the 10 mg group, compared with 25.9 percent in the placebo group.
Use of dapagliflozin was also associated with weight loss. After 24 weeks, the amount of weight lost was 2.21 kg in the 2.5 mg dapagliflozin group, 3.04 kg in the 5 mg group, and 2.86 in the 10 mg group, compared with 0.89 in the placebo group. Another benefit associated with dapagliflozin was a reduction in blood pressure, and no patients experienced hypotension.
Generally, the occurrence of side effects was about equal across all four groups. Rates of genital infections were higher among patients treated with dapagliflozin than those taking placebo, but the infections were mild and did not cause any patients to withdraw from the trial.
Dapagliflozin is not the only diabetes drug in the news lately. Some of the following drugs have been found to have possible uses other than for treatment of type 2 diabetes.
If approved, dapagliflozin will join numerous other drugs designed for treatment of type 2 diabetes, although it will be the first in the class of SGLT2 inhibitors. Along with being both safe and effective, dapagliflozin (along with metformin) only requires once-a-day dosing.
American Diabetes Association
AstraZeneca news release October 2, 2009