Basic HTML Version
DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
98
VOLUME 9 NUMBER 2 • JUNE 2012
Drug Trends
Liraglutide launched in South Africa
T
he exciting promise of liraglutide (Victoza)
in the treatment of type 2 diabetes rests
on three pillars. These are enhanced beta-
cell functioning and good glycaemic control
without weight gain or hypoglycaemic
consequences.
The first two pillars of glycaemic control
are in place, with extensive studies showing
that more patients reach their target HbA
1c
levels on liraglutide treatment without
weight gain or induced hypoglycaemia, than
with any other diabetic agents.
1-5
‘The third
pillar, inhibition of beta-cell apoptosis and
preserved beta-cell functioning, has been
shown in animal studies and in isolated
human pancreatic islet cells’,
6
Prof Juris Meier
of St Josef Hospital and Ruhr University,
Bochum, Germany explained at the liraglutide
symposium held in Johannesburg recently.
The symposium was arranged by Novo
Nordisk and included medical specialist
Prof Juris Meier, South African physician, Dr
Adri Kok, and psychologist Liane Lurie, with
added insights from a patient perspective to
complement the clinical views.
Type 2 diabetes patients typically have a
loss of 50% of beta-cell functioning, with
reduced insulin production and deficient
glucagon suppression, which aggravates
optimal blood glucose control. ‘Over time,
with treatment using oral antidiabetic agents
including metformin, various sulphonylureas,
and agents such as pioglitazone, the beta-cell
situation of patients continues to deteriorate
and these agents offer very little protection
from beta-cell loss’, Prof Meier noted. ‘There
is even some evidence from laboratory
studies that agents used in the treatment of
diabetes, such as glibenclamide, also cause
an increase in beta-cell apoptosis and beta-
cell destruction’,
7
he added.
The most significant unmet need in type
2 diabetes management is that the majority
of patients do not reach their glycaemic
targets of an HbA
1c
level less than 7%. Even
as recently as a few years ago, with all the
improvements in diabetes care, 43% of
patients were not at target.
8
The reason for
poor control is fear of hypoglycaemia and
actual hypoglycaemic events as treatment is
intensified from oral agents to insulin.
‘In the ACCORD study,
9
a higher mortality
rate was seen in patients who experienced
severe hypoglycaemic events; in fact therewas
a two-and-a-half-fold increase in mortality in
these patients’, Prof Meier noted. ‘We need to
avoid hypoglycaemia in our strategic choices
of treatment for our patients’, he stressed.
Weight gain is an ongoing problem
in type 2 diabetes. In the UKPDS study of
patients treated for 12 years, there was an
average weight gain of some 8 kg. Even
in recent studies such as the ADOPT study,
patients gained up to 4.8 kg in five years of
diabetes treatment.
Liraglutide as a GLP-1 mimetic offers the
uniquefeatureofenhancedinsulinproduction
and release from the pancreatic beta-cells
only in the presence of hyperglycaemia,
thereby ensuring that hypoglycaemia does
not occur. Liraglutide also stimulates the
delta-cells, leading to somatostatin release
and glucagon suppression.
‘While early use of liraglutide in the
management of type 2 diabetes is advocated,
the agent is effective across all levels of
remaining beta-cell function, perhaps also
due to its glucagon action’, Prof Meier noted.
This has been shown in a meta-analysis
presented by Prof Meier at the most recent
EASD meeting held in Paris last year.
10
Liraglutide is easy to administer sub-
cutaneously using an injectable pen, in a
starter dose of 0.6 mg, with the majority of
patients (80%) requiring a 1.2-mg dose daily.
A larger dose of 1.8 mg is also available.
Side effects are nausea and gastrointestinal
disturbances.
Physicians are advised to withdraw the
drug in the event of acute pancreatitis in a
patient taking liraglutide. ‘There are however
no significant additional risks of pancreatitis
with this drug’, Prof Meier noted. C-cell
hyperplasia was noted in animal studies
but ongoing post-marketing evaluation of
the marker calcitonin has not shown any
concern with regard to this cancer, which in
addition, is extremely rare in humans.
South African expert view on the
new agent
The launch of Novo Nordisk’s GLP-1
analogue liraglutide (Victoza) marks a new
direction in the treatment of type 2 diabetes
for South African clinicians in that if offers
both patients and doctors a drug that helps
meet their expectations of what a treatment
should deliver.
Speaking at the launch on 28 February, Dr
Adri Kok, a Johannesburg-based specialist
physician in private practice who, over the
past year, has treated 17 patients specially
motivated under section 21, described
liraglutide as ‘a product that can really make
a difference to a patient, a magnificent
alternative to what is currently available.
We’re not just talking about theoretical
scientific results’, she says. ‘Liraglutide works
in patients.’
A key differentiator is that patients on
liraglutide lose weight. This is not the case
with other diabetes treatments, which
tend to be weight neutral or actively
promote weight gain. Dr Kok underscores,
however, that liraglutide is not a weight-loss
treatment, but a treatment for diabetes that
has this as an added benefit. ‘One of the
most important characteristics of liraglutide
is that it has a central nervous system effect,
increasing satiety while also slowing the
passage of food through the gut, allowing
the patient to feel fuller for longer.’
Only one of Dr Kok’s patients has
discontinued liraglutide because he
experienced nausea and vomiting. The
other 16 have done ‘phenomenally’ on the
treatment. Not only have they experienced
weight loss ranging from 10 to 35 kg,
but improved control of their diabetes as
assessed by HbA
1c
levels. ‘And these benefits
have been maintained over six to 12 months,
without the tapering off in efficacy so often
seen with other agents’, continues Dr Kok.
‘Liraglutide is well tolerated, easy to
administer and titrate, and there are no
adverse reactions at the injection site. In
addition, it has benefits in respect of beta-
cell protection and no risk of hypoglycaemia
unless combined with another agent such
as a sulphonylurea, which carries the risk of
hypoglycaemia.’
Because of funding restrictions, doctors
will need to motivate for particular patients
to be prescribed liraglutide. Dr Kok feels
it is especially advisable in patients with a
body mass index above 30 kg/m
2
, in whom
New agent supports weight-loss efforts and improves glucose control without hypoglycaemia