Diabetes drugs and devices:

Diabetes is a chronic (lifelong) disease
marked by high levels of sugar in the
Type 1 diabetes is a chronic (lifelong)
disease that occurs when the
pancreas does not produce enough
insulin to properly control blood sugar
Type 2 diabetes is a chronic (lifelong)
disease marked by high levels of sugar
(glucose) in the blood. Type 2
diabetes is the most common form of

In April 2012 Novo Nordisk announced  
that the FDA has approved Levemir for
a pregnancy Category B classification.  

Levemir,, when used in pregnant
women with diabetes, did not increase
the risk of harm to the unborn baby.

The FDA category change was based
on a review of a large, randomized
controlled trial examining Levemir in
pregnant women with type 1 diabetes.
The study compared the safety and
efficacy of Levemir against NPH insulin
in the treatment of 310 women. The
study found that patients taking
Levemir had similar A1C reduction at
gestational week 36 and lower fasting
plasma glucose levels at gestational
weeks 24 and 36 compared with NPH.
Additionally, the study found no
differences in the overall safety profile
during pregnancy, on pregnancy
outcomes or the health of the fetus
and newborn.

In January 2012 Amylin
Pharmaceuticals received FDA
approval for its diabetes drug
Bydureon, setting the stage for a
commercial battle against an
established rival drug from Novo

Bydureon's U.S. approval comes on its
third attempt. The U.S. Food and Drug
Administration rejected the diabetes
drug last in October 2010, asking
Amylin to conduct an additional study
to assuage concerns about any
possible negative effects the drug may
have on heart rhythm.

Bydureon is a longer-acting version of
Amylin's current diabetes drug Byetta
that will compete against Novo
Nordisk's Victoza. Both Bydureon and
Victoza belong to the growing GLP-1
class of diabetes drugs that stimulate
the release of insulin when a person's
blood sugar gets too high. The drug
delivery technology that allows
Bydureon to be injected once a week
comes from Alkermes, which receives
a royalty on Byudreon's worldwide

Bydureon's main advantage is that
patients only need to inject the drug
once a week. Victoza must be injected
once daily.

Many investors have been less
confident in Amylin's ability to succeed
with Bydureon because the drug's long-
delayed approval has allowed Novo to
gain a strong hold of the GLP-1
market. Amylin must also sell Bydureon
alone in the U.S. following the
departure of its former partner Eli Lilly
(LLY). In Europe, where Bydureon is
already for sale, Amylin is seeking a
new marketing partner to replace Lilly's
commercial efforts.

Novo Nordisk's diabetes drug Victoza
has been on sale in the  U.S. market
since February 2010 for treatment of
type-2 diabetes. The once-daily
injected product is just the second
drug in the new-generation GLP-1
category, rivalling Byetta from Eli Lilly
& Co.  and Amylin Pharmaceuticals

GLP-1 is short for glucagon-like
peptide 1, a naturally occuring
compound that works on different
organs to lower the levels of blood
sugar. For overweight diabetics, there’
s another benefit: GLP-1 attaches to a
receptor in the brain to decrease
appetite, which over time, leads to
weight loss.

Taking the diabetes drug Actos every
day reduced the chance of developing
Type 2 diabetes by two-thirds in
people whose obesity, ethnicity, family
history and other factors put them at
high risk of developing the disease,
researchers found.

In a study of more than 600 high-risk
patients, only 2.1% of those who took
Actos, known generically as
pioglitazone, progressed to diabetes
each year over the three years of the
study, compared with 7.6% of those
who took a placebo, according to the
report in the New England Journal of

All of the patients selected for the trial
had a condition called prediabetes, in
which the body's ability to control blood
sugar levels is already impaired,
although not to the level that would
constitute diabetes.

"The ability to intervene at a
prediabetic state before we become
diabetic and become at risk for
complications is extremely important,"
said Dr. Ralph A. DeFronzo of the
University of Texas Health Science
Center in San Antonio, lead author of
the study.

The study was sponsored by the
drug's maker, Takeda
Pharmaceuticals, and conducted by
researchers at eight academic centers.

About 27 million Americans are
diabetic and about 79 million have
prediabetes, according to the most
recent statistics from the Centers for
Disease Control and Prevention. About
1 in 3 of those who have prediabetes
will progress to diabetes without

Many interventions have been
attempted. The diabetes drug
metformin reduces progression to
diabetes by about 31%. Lifestyle
changes and dieting reduce it by about
58%. Rosiglitazone, sold under the
brand-name Avandia, has been shown
to reduce progression by 62%, but
because of cardiac concerns, the
Food and Drug Administration has
restricted use of the drug to patients
who cannot achieve control of blood
sugars by any other method.

Actos reduced progression to diabetes
by 72%, according to the study.

Faustman is a controversial
researcher at the Massachusetts
General Hospital.  If she is right, it
would mean a revolution in the
treatment of Type  1 diabetes.

Every day in the United States, about
40 children are newly diagnosed with
type 1 diabetes.  

It had long been believed that after the
destruction of insulin-secreting beta
cells in the pancreas of such children,
the cells are gone forever.

However, recent clinical trials led by
Dr. Denise Faustman suggest
otherwise. It appears that the pancreas
can be regenerated to begin
producing insulin by applying doses of
BCG (bacillus Calmette-Guerin), an 80-
year-old tuberculosis vaccine.

The recent human trial involving six
patients – which followed six
experiments on laboratory mice – was
presented  in a June 2011 meeting of
the American Diabetes Association in
San Diego, Calif.

The BCG works by elevating TNF
(tumor necrosis factor) in the
bloodstream. TNF is a protein of the
immune system which blocks attacks
on the pancreas by T cells. More trials
are needed with higher concentrations
of BCG, which will be possible only
after permission is granted by the
Food and Drug Administration (FDA). If
successful, these trials will enable
children with juvenile diabetes to enjoy
what their cohort takes for granted:
normal blood sugar levels.

The majority of people with diabetes
who had bariatric surgery to lose
weight were able to stop taking their
diabetes medications, which led to a
significant decline in health-care costs,
according to a recent study.

Researchers at Johns Hopkins in
Baltimore, looked at 2,235 adults who
had the stomach-reducing surgery and
who also had Type 2 diabetes, a
common form of the disease often
associated with weight gain. Six
months after surgery, nearly 75% of
patients had eliminated their diabetes
medications and after two years 84.5%
of patients were off medicine.

The study was  published in the
Archives of Surgery, a Journal of the
American Medical Association.

It is awfully tough to get effective oral
delivery of a big, unwieldy protein.
Acids and enzymes in the
gastrointestinal tract will chew up a
valuable therapeutic protein as easily
as they’ll tear into a bite of steak.

An injection or IV drip may be perfectly
reasonable for diseases like cancer,
where drugs are usually given in a
hospital setting, but for chronic
diseases like diabetes or multiple
sclerosis, which require daily or weekly
injections, a pill would be much more

Companies are especially keen to
develop alternative delivery solutions
for insulin. Not only would it represent
a major advance for patients, but the
market for a better-acting and easier-
to-use insulin would be gigantic—
insulin sales account for about $15
billion of the global diabetes market.

Attempts at inhaled insulin have been
a colossal failure.

Here are some of the current attempts
in clinical trials:
–India’s Biocon is developing IN-105,
an insulin molecule conjugated to a
short-chain polyethylene glycol
derivative. The technology was
originally developed at N.C.-based
Nobex, which Biocon bought in 2006.

–Ireland’s Merrion Pharmaceuticals is
using technology acquired from Elan
Corp. to enhance gastrointestinal
permeation. In 2008, the company
began working with Novo Nordisk on
solid oral forms of insulin analogs; the
first such analog was put into Phase I
trials by Novo in late 2009.

–N.J.-based Emisphere Technologies
is working with Novo Nordisk on GLP-1
analogs. In January, Novo started a
Phase I trial of the first candidate using
Emisphere’s Eligen technology.

–Israel’s Oramed is using capsules
with an enteric coating, which controls
where in the intestinal tract a pill is
absorbed. A Phase IIb trial of ORMD-
0801 conducted in South Africa
showed the drug to be safe and to
have a clinical impact on insulin and
gluose levels.

–Dallas-based Access
Pharmaceuticals is using insulin-
containing nanoparticles coated with
vitamin B-12 analogs, which pull the
complex into circulation.

GlySens Inc is currently developing an
implantable long term continuous
glucose monitoring sensor that is
designed to provide an unobtrusive
means to continuously track glucose
levels and improve the lives of people
with diabetes.
An initial system release will comprise
two elements: the  fully implanted
sensor and an external monitor with a
The sensor resides completely under
the skin and continuously monitors the
glucose levels, which are correlated to
blood glucose levels. The sensor
transmits the glucose measurements
wirelessly to a convenient external
display device. This device indicates
the current blood glucose level, shows
a historical chart of the previous blood
glucose values, provides adjustable
automatic warnings of high and low
blood glucose readings, and stores
information for easy analysis by the
user or physician.

A recent major clinical trial funded by
the Juvenile Diabetes Research
Foundation concluded that patients
using continuous glucose monitoring
devices experienced significant
improvements in glucose control. Over
the long term, this improvement in
control is expected to lower the risk of
complications for people with diabetes

"Four finger sticks per day to measure
glucose levels is the current standard
of care, but blood glucose can go on
significant excursions between sticks,"
says David Gough, an author of the
study from the University of California
in San Diego. “In contrast, the long-
term implanted glucose monitor would
provide continuous monitoring day and

In January 2012 this drug has failed to
win U.S. clearance  as regulators
sought more data on the medicine’s

A new class of drugs being developed
to treat Type 2 diabetes showed the
potential to help lower blood glucose
levels through a different mechanism
than current treatments.

Dapagliflozin, is being developed by
Bristol-Myers Squibb Co.  and
AstraZeneca PLC. The product is
designed to lower blood glucose levels
in patients with diabetes by increasing
the amount of glucose excreted in the

Dapagliflozin as well as canagliflozin, a
similar product being developed by
Johnson & Johnson (JNJ), inhibit
sodium-glucose transporter-2 system
used by the kidneys to filter and
reabsorb glucose circulating in the
blood. The products are known as
SGLT2 inhibitors.
Data from an advanced Phase 3 study
of dapagliflozin involving 807 patients
with diabetes who were on insulin
showed the drug helped lower A1C
blood hemoglobin levels, a common
measurement of blood glucose,
compared to those receiving a placebo.
The study also showed patients in the
dapagliflozin group lost slightly more
weight than patients in the placebo
group and had a drop in blood

However: Nine cases of bladder cancer
occurred in male patients who took
dapagliflozin, compared with one case
among people treated with a placebo.
Breast cancer occurred in nine
patients who took dapagliflozin, and
one patient in the control group. FDA
staff also said the drug was less
effective in patients with impaired
kidney function.

“We believe pretty strongly that this will
be an uphill battle for the panel and
that FDA will almost definitely seek
more information before approving
dapagliflozin,” an analyst said.

Dapagliflozin would be the first in a
new class of treatments called SGLT2-
inhibitors that work by letting patients
excrete excess blood sugar in their
urine. Johnson & Johnson, Eli Lilly &
Co. (LLY), Boehringer Ingelheim
GmbH, and Astellas Pharma Inc. are
among the companies pursuing similar

Otelixizumab, also known as TRX4, is a
novel monoclonal antibody  which is  
developed for the treatment of type 1
diabetes and other autoimmune
diseases. Developer: Tolerx, Inc. in
collaboration with GlaxoSmithKline and
it is manufactured by Abbott
Tolerx, Inc. announced the initiation of
a confirmatory Phase 3 clinical trial
that is called DEFEND-2 and
immediately follows successful
completion of enrollment in the initial
Phase 3 clinical trial, DEFEND-1, with
results from DEFEND-1 expected in
the first half of 2011.

"For decades, our primary treatment
option for patients with type 1 diabetes
has been the use of insulin alone to
control blood glucose levels, while the
underlying autoimmune disease
continues to progress," said Dr.
Thomas B. Repas, Clinical Assistant
Professor, Department of Internal
Medicine, University of South Dakota,
Sanford School of Medicine, and an
investigator in the DEFEND-2 study.
"The future potential of otelixizumab
opens up the opportunity for an
entirely new treatment approach that
can intervene at early onset of type 1
diabetes and potentially break the
cycle of the continued progression of
this disease that patients manage over
their entire lifetime."
Otelixizumab targets CD3, a T
lymphocyte receptor involved in normal
cell signaling. Data suggest that the
antibody may work in patients with type
1 diabetes who have residual beta
cells by blocking the function of
effector T cells that mistakenly attack
and destroy insulin-producing beta
cells, while stimulating regulatory T
cells that are understood to protect
against effector T cell damage, thus
preserving the beta cells' ability to
make insulin.
DEFEND-2 is a randomized, placebo-
controlled confirmatory Phase 3 trial
designed to enroll up to 400 patients,
age 12 to 45, with newly diagnosed
autoimmune type 1 diabetes. DEFEND-
2 is being conducted at more than 200
sites in North America and Europe.

Last September, Medtronic began
marketing in Europe its most advanced
diabetes device. Known as Paradigm
Veo, the device can automatically halt
insulin delivery from a pump when
sensors detect that a patient’s blood
sugar has fallen below safe levels.
Severe low blood sugar, or
hypoglycemia, is a dangerous
condition that may cause loss of
consciousness, seizures, comas or
even death.

Medtronic’s MiniMed Paradigm system
used in a current study combines a
glucose monitor, a hair-thin wire
inserted just beneath the skin and a
tiny transmitter that sends blood-sugar
readings to a mobile phone-size insulin
pump that is worn on the body. The
monitor provides glucose readings
about every five minutes to the pump,
which delivers insulin through a small
soft tube and a needle stick. The pump
can graph blood sugar trends, allowing
the patient to adjust their insulin levels.

The U.S. market for continuous
glucose monitors may reach as much
as $4 billion if half of the nation’s
insulin-dependent diabetics used the
The Medtronic system is only part way
to the goal of an “artificial pancreas”
that doctors envision: a computer-
controlled device to monitor glucose
continuously and release insulin
without any patient effort. Early, semi-
automated versions of a computer-
driven artificial pancreas may reach
the market in four years.
Medtronic is competing with other
makers of insulin pumps or round-the-
clock glucose monitors including San
Diego-based DexCom Inc., Bedford,
Massachusetts-based Insulet Corp.,
Abbott Park, Illinois-based Abbott
Laboratories and New Brunswick, New
Jersey-based Johnson & Johnson.
ACCU-CHEK Aviva Test Strips are for
testing glucose in whole blood. For use
with ACCU-CHEK Aviva.