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VOLUME 10 NUMBER 4 • NOVEMBER 2013
REPORT
SA JOURNAL OF DIABETES & VASCULAR DISEASE
N
ovo Nordisk and Roche Diagnos-
tics co-hosted the Diabetes Update
Symposium, a satellite session affili-
ated to the August 2013 Centres for Dia-
betes and Endocrinology (CDE) meeting
held in Boksburg. Novo Nordisk celebrated
a milestone 90th birthday in 2013. In open-
ing remarks, Dr Timmy Kedijang (general
manager, Novo Nordisk SA) reaffirmed that
as one of the first companies to produce
insulin, Novo Nordisk remains committed
to innovation in diabetes care in a socially,
environmentally and financially sustainable
manner.
The dilemma of positioning
incretins in type 2 diabetes
Dr Aslam Amod, endocrinologist
Pharmacological options for the man-
agement of diabetes have increased sig-
nificantly during recent years, with the
development of new drug classes and the
registrationofmany individual agentswithin
these classes. An existing evidence base for
treatment options places metformin for
use in first-line therapy and the addition of
sulfonylureas (SUs) for use in second-line
therapy. Classes with an evidence base for
use as both second- and third-line therapy
are insulin, DPP-4 inhibitors, GLP-1 agon-
ists, alpha glucosidase inhibitors and TZD.
A conundrum is thus placed in the hands
of the treating practitioner, as this evidence
base furnishes 50 possible therapy combi-
nations between classes and 1 440 therapy
combinations between individual agents.
Recently updated guidelines from the
ADA, EASD and AACE/ACE all provide multi-
ple therapy options. This is of little assistance
to practitioners who are not diabetologists.
The 2012 SEMDSA treatment algorithm for
type 2 diabetes offers a narrower range of
preferred therapies, with alternative thera-
pies for special circumstances.
Dr Amod outlined an ideal diabetes
therapy, his ‘utopiglutide’, as being strong
in glycaemic control, with established
reductions in microvascular, macrovascu-
lar and mortality outcomes. The therapy
Novo Nordisk – Accu-Chek
®
Diabetes Update Symposium
The journey towards glycaemic control: is it influenced by drug of choice
or inertia?
would result in no hypoglycaemia or side
effects, weight loss (or no weight gain) and
other non-glycaemic benefits. This therapy
would also be affordable, with high patient
acceptability. Dr Amod went on to con-
textualise the well-validated and newer
therapeutic options in attaining a balance
between the benefits of glycaemic control
and improved outcomes against the disad-
vantages of hypoglycaemia, weight gain
and side effects.
Metformin should be the cornerstone
of therapy. Extensive experience and data
show a strong glycaemic effect, with mac-
rovascular benefit. UKPDS data indicate a
mortality risk reduction of 40%. Metformin
is safe, weight neutral/beneficial and has
high patient acceptability. Of importance,
metformin is inexpensive, with many afford-
able generics available. However, metformin
displays no microvascular benefits, gastroin-
testinal intolerance is experienced in 10 to
30% of patients, and currently there are
concerns of increased mortality when used
in combination with SUs.
Metformin is the preferred first-line
therapy as per the 2012 SEMDSA guide-
lines. Should the patient prove intolerant,
he/she could try the extended-release for-
mulation. If intolerance remains an issue, it
can be replaced with any of the following:
gliclazide or glimepiride, a DPP-4 inhibitor,
acarbose or a GLP-1A injectable.
Upon metformin failure, the preferred
SEMDSA recommendation entails adding
an SU to current metformin therapy. It is a
common perception that SUs are not safe,
with a propensity to weight gain, risk of
hypoglycaemia and increased cardiovascu-
lar events.
The second-generation SUs (gliclazide,
glimepiride and glipizide) are newer and
safer options. These have a strong gly-
caemic effect with reduced microvascular
and mortality outcomes, have high patient
acceptability, and are inexpensive. Gli-
clazide provides better results for hypogly-
caemia (GUIDE study) and is weight neutral
(ADVANCE study). Gliclazide is also the only
SU that is not associated with an increased
cardiovascular risk.
In patients with renal concerns, gliben-
clamide is the most dangerous and should
not be used where the glomerular filtration
rate (eGFR) is < 60 ml/min. Dr Amod sug-
gests gliclazide or glimepiride as the SU of
choice, based on efficacy, safety, evidence-
based outcomes and cost. Acarbose or an
incretin should be used in lieu of an SU in
cases where frequent or severe hypoglycae-
mia occurs, circumstances exist wherein the
risk of severe hypoglycaemia and its conse-
quences would be significant and/or cata-
strophic (e.g. workers with frequent rotating
shifts or heavy machinery operators), or
weight gain has occurred and carries unac-
ceptable obesity-related morbidity risks.
Upon failure of second-line therapy, Dr
Amod recommends the addition of basal
insulin to the existing therapy. Insulin is
strong in glycaemic benefit, as well as
microvascular, macrovascular and mortality
benefit. However, high rates of hypogly-
caemia and weight gain result in very low
patient acceptability. Acarbose or an incre-
tin should be used in lieu of insulin for the
same reasons mentioned with SU substi-
tution. Other circumstances where insulin
therapy may not be desirable include insu-
lin allergy, as well as failure or inability to
master injections or self-titration.
DPP-4 inhibitors have a moderate gly-
caemic effect, with the advantages of low
rates of hypoglycaemia and being weight
neutral. Adverse events are similar to pla-
cebo; however renal, hepatic and derma-
tological concerns have been raised. DPP-4
inhibitors are expensive, although patient
acceptability is high.
GLP-1A shows strong glycaemic benefit,
but there are currently no benefit data for
microvascular, macrovascular and mortality
outcomes. There are low rates of hypogly-
caemia, unless used in combination with an
SU, and the weight benefit is variable with
a mean weight loss of 2.5–3.5 kg. Side
effects of GLP-1A are predominantly gas-
trointestinal. These agents are very expen-
sive, with variable patient acceptability.
Concerns have been raised surrounding
increased risk of pancreatitis and pancre-
atic cancer with the use of DPP-4 inhibitors
