Dapagliflozin maintains HbA1c control as companies seek to bolster case for approval

December 19, 2011

written by Michael O’Leary

Dr. Krzysztof Strojek

Adding dapagliflozin to glimepiride (Amaryl®) maintained reductions of blood sugar levels over nearly six months, in an extension of a study that had already shown that the combination of type-2 diabetes drugs was better than either drug alone.

The Polish study, extended to add data to the case for FDA approval of dapagliflozin by AstraZeneca and Bristol-Myers Squibb, was presented at the Diabetes Federation World Diabetes Congress in Dubai, United Arab Emirates this past week. (Link to published site)

Led by Dr. Krzysztof Strojek, of Silesian Medical University in Katowice, Poland, the study originally was a 24-week trial that enrolled 592 adults with type 2 diabetes and an HbA1c between 7 percent and 10 percent at the start of the study.

After 24 weeks, the results showed that 46.6 percent of patients in the combination group had an HbA1c level of 7 percent or less compared with 35.2 percent with metformin alone and 31.7 percent with dapagliflozin 10 mg alone. In addition, the patients in the dapagliflozin groups achieved an average weight loss of seven pounds.

Last July, however, an FDA advisory committee voted against recommending approval of the drug due to concerns that it could increase risk of cancer and cause liver injury. There have been nine breast cancers and nine bladder cancers among 5,478 patients in previous studies among the dapagliflozin groups compared to only 1 breast and bladder cancers among the 3,156 patients assigned to comparison groups.

Following that vote, the drug companies extended this study another 24 weeks. A total of 546 patients stayed on with the study, and after the entire 48 weeks the results as reported by MedPage Today showed that the reduction in blood sugar over the first 24 weeks were sustained over the following 24 weeks.

Side effects also remained similar to those reported earlier with the most common including: inflammation of the nasal passages, back pain, upper respiratory tract infection, bronchitis, cough, urinary tract infection, imbalances in fats in the blood, high blood pressure, joint pain, diarrhea, genital infections, and upset stomach. These were experienced by at least 3 percent of the patients in each of the groups given dapagliflozin.

Dapagliflozin works with a more comprehensive mode of action than DPP-4 (Onglyza®, Januvia®) and GLP-1 (BYETTA®) by slowing or blocking absorption of glucose in the kidneys so that sugar is excreted in the urine.

AstraZeneca and Bristol-Myers Squib funded the Polish study, and Dr. Strojek has been paid by the companies for speaking about the drug at conferences. The other authors on the study are all employed by the companies.