* Better glucose control than Januvia or glimepiride
* Significant weight loss seen with JJ’s canagliflozin
* Far less hypoglycemia than glimepiride with canagliflozin
* Canagliflozin has been submitted to FDA for approval
By Bill Berkrot
June 9 (Reuters) – An experimental treatment for type 2
diabetes developed by Johnson Johnson demonstrated
greater reduction in blood sugar than Merck Co’s
Januvia and an older common treatment, glimepiride, according to
data from a pair of late stage clinical trials.
The JJ 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 JJ
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 JJ 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, JJ said.
The JJ 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
STRIKING WEIGHT LOSS
The 1,450-patient canagliflozin versus glimepiride trial
studied two doses of the JJ 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 JJ 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 JJ drug led to increases in both good
and bad cholesterol and a small but favorable decrease in blood
Canagliflozin was also associated with higher rates of
genital infections, urinary tract infections and need for
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 JJ drug.
“We reported some favorable reduction in liver enzymes,”