DIABETES NEWS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
34
VOLUME 7 NUMBER 1 • MARCH 2010
normal but not yet high enough to qualify
as diabetes). The most common side effects
of liraglutide were nausea and vomiting.
Patients did not seem to mind injecting the
drug, the authors noted.
‘The original one-year, randomised
trial that appeared in the
Lancet
last year
[2009;
373
(9662): 473–481] showed
[that liraglutide] was about twice as effec-
tive as a traditional means of stimulating
insulin secretion using a sulfonylurea, and
[the response] was fairly durable over the
full year of the randomised trial’, said Dr
Garber.
At the IDF meeting, Dr Garber pre-
sented data on a two-year follow-up that
was conducted in 440 of the 473 patients
who completed LEAD-3.
Overall, 321 patients completed the full
two years of treatment. Compared with
glimepiride, treatment with liraglutide
resulted in significantly greater reductions
in HbA
1c
and a lower final HbA
1c
(6.9%with
1.2 mg of liraglutide and 7.1% with 1.6
mg of liraglutide vs 7.5% with glimepir-
ide). Liraglutide therapy was also associ-
ated with a greater proportion of patients
achieving HbA
1c
levels of less than 7% or
of 6.5% or more without hypoglycaemia
or weight gain, greater reductions in fast-
ing plasma glucose (FPG), and lower final
FPG values (7.45 and 7.58 vs 8.54 mmol/l,
respectively), greater reductions in mean
daily postprandial glucose, and weight
loss. Patients receiving glimepiride actually
gained a mean of 1.0 kg.
‘In the second-year extension that we’re
showing here, you get the same persistent
A
1c
control at full dose as what you saw at
one year’, said Dr Garber. ‘So, it appears to
be a very stable, durable effect. There is no
weight regain while on the drug, and it’s
very well tolerated.’
Despite lower HbA
1c
values with liraglu-
tide, this therapy actually caused fewer
hypoglycaemic events than with glimepir-
ide. There were 0.21 hypoglycaemic events
per patient-year with 1.2 mg of liraglutide
and 0.22 events with 1.8 mg of the drug,
compared with 1.75 events per patient-
year with glimepiride. The most frequently
occurring adverse events with liraglutide
were nausea and diarrhoea.
IDF delegateGeorge Fantus, MD, FRCPC,
associate dean of research at the University
of Toronto and professor of medicine at
Mount Sinai Hospital in Toronto, Ontario,
stated that the key issue with incretin-
based therapies, such as liraglutide, will be
whether they truly protect beta-cells.
‘That’s the key issue with the incretins:
whether over the long term there is going
to be more success and less progression
to require insulin using these drugs as
opposed to sulfonylurea’, he said. ‘The
weight loss is expected and has been dem-
onstrated previously. Less hypoglycaemia is
expected because its [actions of] lowering
glucose and [promoting] insulin secretion
are glucose-dependent. Sulfonylureas, it’s
well known, are not glucose dependent, so
there is hypoglycaemia.’
‘The other question is about the [risk
for] complications’, said Dr Fantus. ‘There’s
a hint of pancreatitis or thyroid problems,
which [might] be significant. It’s too early
to say .... I think these things usually come
out in post-marketing, with large numbers
of people in the real world.’
International Diabetes Federation (IDF),
20th World Diabetes Congress: Abstract
P-1397. Presented October 21, 2009.
Stop press: liraglutide approved for
type 2 diabetes
The US Food and Drug Administration
(FDA) recently approved liraglutide (rDNA
origin) injection (Victoza, Novo Nordisk)
for the treatment of type 2 diabetes in
adults.
1,2
Liraglutide is the first once-daily human
glucagon-like peptide-1 (GLP-1) analog
indicated for the treatment of type 2 dia-
betes. The new treatment is indicated
in conjunction with diet and exercise to
improve blood sugar control in adults with
type 2 diabetes failing first-line therapy. It
can be prescribed as monotherapy or in
combination with other oral antidiabetic
medications.
The approval was based on results from
the Liraglutide Effect and Action in Dia-
betes (LEAD) phase 3 trials, including five
studies of 26 to 52 weeks’ duration and
involving more than 3 900 patients. As a
single agent and in combination with other
antidiabetes agents, liraglutide significantly
reduced haemoglobin A
1c
, with reductions
for liraglutide 1.8 mg, in combination or
as monotherapy, ranging from 1.0 to
1.5%, in patients with baselines from 8.2
to 8.6%. Overall, liraglutide 1.8 mg with
metformin reduced A
1c
by 1.0%.
Liraglutide was also associated with
weight loss compared with comparator
arms. Liraglutide 1.8 mg or metformin
reduced weight by 6.2 lbs (2.8 kg).
Common adverse reactions noted included
headache, nausea, diarrhoea and anti-
liraglutide antibody formation. Immuno-
genicity-related events such as urticaria
were also reported.
The FDA is requiring the company to
conduct several post-marketing studies
to ascertain additional information on the
safety of liraglutide, including a five-year
epidemiological study using a health-claims
database to evaluate thyroid and other
cancer risks as well as risks for hypoglycae-
mia, pancreatitis and allergic reactions, the
FDA said in a press release.
A 15-year cancer registry that will evalu-
ate the risk of medullary thyroid cancer
is also required. According to the FDA, a
proposed risk evaluation and mitigation
strategy will ‘ensure that the benefits of
the drug outweigh the risk of acute pan-
creatitis and the potential risk of medullary
thyroid cancer.’
According to the company, liraglu-
tide has not been studied ‘sufficiently in
patients with a history of pancreatitis’. In
addition, liraglutide should not be used to
treat type 1 diabetes mellitus or diabetic
ketoacidosis and has not been studied in
combination with insulin.
The American College of Endocrinology
recently updated its treatment algorithms
for type 2 diabetes and recommended that
GLP-1 agonists such as liraglutide are a
viable ‘treatment option when blood sugar
goals are not met or maintained with life-
style adjustments and metformin’.
3
The company expects liraglutide will
be available in the USA in the near future;
it has also been approved in Europe and
Japan and is under review in China.
Food and Drug Administration. FDA approves
1.
new treatment for type 2 diabetes. Press
release, 25 January 2010.
Novo Nordisk. Novo Nordisk receives US
2.
approval for Victoza (liraglutide) for the
treatment of type 2 diabetes. Press release,
26 January 2010.
Rodbard H, Jellinger P, Davidson JA,
3.
et al
.
Consensus panel on type 2 diabetes mellitus:
An algorithm for glycaemic control.
Endocrin
Pract
2009;
15
: 540–559.
