By Bill Berkrot
(Reuters) - An experimental treatment for type 2 diabetes developed by Johnson & Johnson proved effective at reducing blood sugar in patients on long-term insulin therapy and at high risk for heart problems, according to a study presented on Tuesday.
The drug, canagliflozin, also led to clinically meaningful drops in blood pressure and weight loss, both of which should be beneficial for diabetics at an elevated risk of heart problems, researchers said.
"It's always a challenge to try and reduce weight, reduce blood glucose, reduce blood pressure and here you've got an agent which will help you to reduce weight, blood sugar and blood pressure all in one go," David Matthews, one of the study's lead researchers, said in a telephone interview.
The data, from an 18-week sub-study of more than 1,700 patients, was culled from a much larger Phase III trial called Canvas that was part of J&J's application package submitted earlier this year seeking U.S. and European approval for canagliflozin. If approved, it would be the diversified healthcare conglomerate's first diabetes medicine.
Patients in the sub-study, which compared the drug at doses of 100 milligrams or 300 mg to placebo, suffered from type 2 diabetes on average for 16 years and were on insulin therapy for an average of seven years, having progressed from other medicines. More than half had a history of prior heart attacks, strokes or vascular problems.
After 18 weeks of daily treatment, A1C - a common measure of blood sugar - was reduced by 0.65 percent in patients taking 100 mg of canagliflozin and by 0.73 percent at 300 mg versus virtually no change on placebo.
"These are clinically significant drops, no doubt about it," said Matthews, a professor of diabetes at the Oxford Centre for Diabetes, Endocrinology & Metabolism in Oxford, England.
The results were presented at the European Association for the Study of Diabetes (EASD) meeting in Berlin.
Patients on canagliflozin experienced modest increases in both bad LDL cholesterol and good HDL cholesterol. The increase in LDL could be a cause of concern for heart patients, but might be balanced somewhat by the HDL increase, Matthews said.
The J&J drug also led to statistically significant reductions in systolic blood pressure at both doses (-2.6 mmHg and -4.4 mmHg), as well as reductions in diastolic blood pressure, or both ends of the blood pressure reading.
"Blood pressure certainly comes down in significant amounts, in fact in amounts that you would regard to be quite respectable in an anti hypertension agent," Matthews said.
The low dose of canagliflozin led to an average weight loss of about 1.8 kilograms (4 pounds) and those on higher dose lost an average of 2.3 kg (5 lbs) after 18 weeks of treatment.
Weight loss is a particularly attractive effect because obesity is a primary cause of type 2 diabetes and some older treatments 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.
Deaths among the high risk patients in the study was about even with five in the placebo group and two each in the drug groups.
Most adverse events were deemed to be mild to moderate, although the incidence of discontinuation due to side effects was higher in the 300 mg group at 5.3 percent versus 1.9 percent for 100 mgs and placebo.
The most common side effect was genital infections, which Matthews said occurred in about 10 percent of women and six percent of men taking the drug. Other side effects included increased urination and hypotension, or low blood pressure.
As with prior canagliflozin studies, researchers did not see signs of the liver problems that contributed to an FDA rejection of dapagliflozin, a drug from AstraZeneca Plc and Bristol-Myers Squibb Co that belongs to the same SGLT2 class.
"All in all, you've got no real safety signal coming out of the liver or the renal aspects (kidneys) that would give cause for concern," Matthews said.
"In terms of serious AEs (adverse events) there's really no signal at all. The results from this sub study suggest that canagliflozin could provide an important new treatment option for higher risk adult patient with type 2 diabetes."
And because canagliflozin worked well on top of insulin, it might prove to be a viable treatment to help type 1 diabetics as well, he added.
(In fourth to last paragraph, this story corrects to say "researchers did not see signs," adding the word "not")
(Reporting by Bill Berkrot in New York. Editing by Andre Grenon)