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VOLUME 9 NUMBER 1 • MARCH 2012
31
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REPORT
I
n a new direction for Sanofi, the general
manager, John Fagan pointed out that not
only is diabetes a key focus area for Sanofi,
‘but we also need to go beyond traditional
pharmaceutical research and development in
our focus. Together with clinicians, we need
to think about the patient first, then about
the product, and do competent research
and development to meet patients’ unmet
needs’, he said. This approach is reflected in
the Diabetes Division’s new slogan, ‘Going
beyond, together’.
In the special briefing at the recent Sanofi
specialist meeting held in Cape Town, John
Fagan noted that the South African Gov-
ernment’s National Health Insurance devel-
opment looks more cautious, planned, and
inclusive of the private sector than initially
thought, which offers opportunities for both
state- and privately funded healthcare organ-
isations to improve patient care.
‘The ORIGIN outcome trial with strong
South African patient recruitment, which
looks at early insulin therapy with glargine,
will likely present first results at the 2012
American Diabetes Association (ADA) meet-
ing and is an important diabetes care mile-
stone for Sanofi’, he concluded.
The incretins: so much attention
at international meetings that a
review in South Africa is timeous
Dr Larry Distiller, co-ordinator of this special-
ist meeting, set the pace of thorough review
of topics presented at the meeting, by cau-
tioning clinicians to evaluate incretin usage
critically. ‘It is clearly time to review these
agents, both the GLP-1 agonists and the
DPP-4 inhibitors, as their international status
grows and they become more available on
the South African market’, he noted.
‘The defining characteristic of these two
classes of agents are the supra-physiological
levels of GLP-1s attained by exenatide or
liraglutide treatment (the GLP-1 agonists),
and the physiologically stable levels of GLP-1s
attained by the use of DPP-4 inhibitors. The
actions of the injectable GLP-1 agonists are
therefore generally more powerful than that
of the oral DPP-4 inhibitors. The incretins’
enhancement of glucose-induced insulin
secretion and the restoration of the gluca-
gon-suppression response are particularly rel-
evant, as glucagon is certainly the forgotten
hormone of type 2 diabetes’, he said.
Referring to exenatide (twice daily), also
to the more powerful once-weekly dosage
not yet available in South Africa, and liraglu-
tide (once daily), Dr Distiller noted that their
promise is partially fulfilled by the fact that
the reduction in level of HbA
1c
(0.8–1%
reduction depending on baseline HbA
1c
level) is maintained over a two- to three-year
period and there is a progressive and prob-
ably meaningful weight loss.
‘There is considerable interest in the
non-glycaemic potential benefits of GLP-1
agonists with regard to their neuroprotec-
tive and cardioprotective effects.’ A real-life
study in medically insured patients, the Life-
Link study, has recently shown a 16% reduc-
tion in cardiovascular events in patients on
exenatide’, Dr Distiller noted.
1
‘With regard to the ultimate promise of
these agents, the increased proliferation
and reduced apopstosis of
β
-cells, which
was shown in early experimental laboratory
studies, there is some evidence from HOMA
studies that, for example, liraglutide is
β
-cell
sparing, compared to thiaglitazides (TZDs)
and basal insulin. At this juncture, liraglu-
tide appears the better option in this class
of agents, but this situation is dynamic and
may change with the advent of once-weekly
exenatide’, Dr Distiller noted.
‘With regard to the DPP-4 inhibitors’, Dr
Distiller said ‘they work; they are mild and
do not change the world, but they do work.
They are weight neutral, drop HbA
1c
levels
on average by 0.7% and there is a sugges-
tion that they preserve
β
-cell function. Over-
all their cardiovascular effects are not yet as
well researched as the GLP-1 agonists’, he
noted.
With regard to when to use these agents,
Dr Distiller noted that early use when there is
still
β
-cell function is taken up in many algo-
rithms, as an alternative for sulphonylureas
with metformin; also in combination with
insulin, following acceptable trials, and reg-
istration for use of the particular agent with
insulin.
As DPP-4 receptors are widespread in
the body, and despite claimed specificity
of these inhibitors, Dr Distiller noted a gen-
eral acceptance that these drugs have a
subtle effect on the immune-surveillance
system, leading to increased incidence of
bronchitis, for example. With regard to the
GLP-1 analogues and their risk of pancrea-
titis, pancreatic and thyroid cancer, there is
an alert but not yet an alarm, despite the
much-commented article on post-marketing
surveillance’,
2
he concluded.
From promise to gold standard
Dr Joshi, emeritus professor of Medicine,
MEDUNSA
‘Metformin has truly been established as the
foundation, first-line therapy for type 2 dia-
betes’, Prof Joshi noted. Derived from the
Galega officinalis
plant, galegine produced
hypoglycaemia in sheep but was found to
Sanofi specialist diabetes meeting, Cape Town
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