New diabetes drug tops older therapiesom
The J&J drug, canagliflozin, also led to significantly greater weight loss than both of the other drugs and far fewer incidents of hypoglycemia, or potentially dangerous drops in blood sugar levels, than glimepiride, a member of the sulfonylurea class of medicines.
Weight loss is an especially attractive effect as obesity is a leading cause of type 2 diabetes and some older medicines cause weight gain.
Canagliflozin, belongs to a new class of diabetes treatments called SGLT2 inhibitors that work by blocking reabsorption of glucose by the kidney and increases glucose excretion in the urine to lower blood sugar.
The data from the two 52-week studies, presented on Saturday at the American Diabetes Association (ADA) meeting in Philadelphia, are part of a massive approval application J&J submitted to the U.S. Food and Drug Administration last week that comprised nine separate Phase III trials involving more than 10,000 patients. If approved it would be the giant healthcare conglomerate's first diabetes medicine.
"There are clearly some unmet needs in diabetes to get glucose control. Hypoglycemia is a big limitation and right now we don't have effective weight loss therapy, so this class of drugs clearly provides clinical benefits," said Dr. William Cefalu, the primary researcher on the glimepiride study.
"This would be another viable option, another tool in the tool box," Cefalu said of canagliflozin.
In the 755-patient study comparing 300 milligram once-daily canagliflozin to Januvia, the J&J drug provided statistically significant reductions in A1C levels -- a commonly used measure of blood sugar over time.
Canagliflozin led an average drop in A1C levels of 1 percent compared with a drop of 0.6 percent for Januvia, a DPP4 inhibitor known chemically as sitagliptin. Some 47 percent of canagliflozin patients got A1C down to the ADA guideline of 7 or less compared with 35 percent of Januvia patients, J&J said.
The J&J drug led to an average weight loss of 2.5 percent, or about 2.3 kilograms (5 pounds) compared with virtually no impact on weight for the Merck drug. The weight loss for canagliflozin was even more pronounced in the other study.
Patients in the study were already taking metformin -- the most common first treatment option after diet and exercise fails -- and a sulfonylurea.
The rate of hypoglycemia was similar and over 40 percent for both groups, likely largely due to the solfonylureas, which have been associated with high rates of hypoglycemia.
More patients dropped out of the study due to loss of glycemic control in the Januvia group -- 22.5 percent versus 10.6 percent. The rate of serious side effects was low and similar for both drugs, but discontinuation due to serious side effects was higher for canagliflozin -- 5.3 percent vs 2.9 percent.
STRIKING WEIGHT LOSS
The 1,450-patient canagliflozin versus glimepiride trial studied two doses of the J&J drug -- 100 mg and 300 mg -- in subjects already on maximally effective doses of metformin.
A1C reductions were nearly identical for glimepiride and the lower dose of the J&J drug. The 300 mg dose proved to be statistically superior with an average A1C reduction of 0.93 pct compared with 0.81 for glimepiride.
Glimepiride patients on average added about 1 percent to their weight after 52 weeks. The 100 mg canagliflozin led to a 4.2 percent weight reduction and there was a 4.7 percent weight reduction for 300 mg patients, or a difference of about 10 pounds (4.5 kg) versus the older drug.
There was also a big difference in incidence of hypoglycemia in the study. The percentage of patients with at least one episode of hypoglycemia was 4.9 for 300 mg dapagliflozin, 5.6 percent for 300 mg and 34.2 percent for glimepiride.
Aside from glucose control, "the other striking thing was the weight loss and the lack of hypoglycemia," said Cefalu, head of diabetes at the Pennington Biomedical Research Center at Louisiana State University.
In both studies, the J&J drug led to increases in both good and bad cholesterol and a small but favorable decrease in blood pressure.
Canagliflozin was also associated with higher rates of genital infections, urinary tract infections and need for increased urination.
Researchers, however, did not run into concerns over liver damage that contributed to the FDA rejection of dapagliflozin, a drug from AstraZeneca and Bristol-Myers Squibb that belongs to the same class as the J&J drug.
"We reported some favorable reduction in liver enzymes," Cefalu said.
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