DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
114
VOLUME 10 NUMBER 3 • SEPTEMBER 2013
A
number of consistent key messages
came through at Novo Nordisk’s Incretin
and Cardiovascular summit, which took
place in Durban on 29 June 2013. Despite
some superficially conflicting evidence in
clinical studies, early intensive therapy has
long-term cardiovascular benefit in diabetes
patients, consequent on a legacy effect or
‘metabolic memory’, even though these
benefits may take years and even decades
to manifest.
When treating patients, it is imperative
to individualise treatment and keep
cardiovascular safety in mind. While there
was some debate as to whether diabetes
is indeed a cardiovascular disease (CVD)
equivalent, as has been suggested in some
quarters, there is no question that people
living with diabetes are at high risk of
cardiovascular complications. This presents
unique treatment challenges.
Incretin-based therapies are taking the
management of diabetes in new and encour-
aging directions, providing optimal HbA
1c
control, with reduced or no risk of weight
gain and reduced hypoglycaemia. Studies are
on-going to show cardiovascular safety and,
in due course, may even show benefit.
How early and aggressively should
diabetes be treated?
Prof Brynne Ascott-Evans, head of the
Division of Diabetes and Endocrinology,
University of Stellenbosch, Tygerberg
According to Prof Ascott-Evans, the answer
to the question is ‘very early and very
aggressively’. Intervention should begin in
the pre-diabetic stage to reduce risk, slow
progression to overt diabetes and prevent
macrovascular complications. ‘Diabetes is
a late manifestation of the metabolic syn-
drome and a cluster of CVD risk factors is
often already present in pre-diabetes’, said
Prof Ascott-Evans.
Studies have shown good results
with lifestyle modification, but where
these fail and/or in high-risk individuals,
pharmacotherapy should be introduced
early. Prompt tight control of glucose levels
has a legacy effect that reduces the risk of
complications in the long term.
Insulin can be introduced early too, even
though it is not usually recommended as
Novo Nordisk Incretin and Cardiovascular summit
first-line therapy. However, Prof Ascott-
Evans feels that there is sometimes a place
for temporary insulin therapy at diagnosis
in high-risk patients. ‘Several weeks of
insulin therapy can help to normalise blood
glucose levels, where after the patient can
be controlled with diet and metformin.’
Newer therapies such as the incretins have
the promise of protecting beta-cell function.
‘Effective treatment usually requires multiple
drugs used in combination’, he concluded.
‘We need to intervene early in the natural
history of diabetes to prevent progressive
beta-cell failure, and that intervention needs
to be aggressive.’
Choosing appropriate antidiabetic
therapy in patients with CVD
Prof Pankaj Joshi, emeritus professor of
Medicine, Medical University of South Africa
(MEDUNSA)
Type2diabetesmellitus is an independent
•
CVD risk factor and should not be viewed
only as a disease of blood sugar.
The risk of CVD increases as glucose
•
metabolism deteriorates.
Antidiabetic therapy should achieve not
•
only adequate glucose control, but also
favourable cardiovascular safety profiles
and outcomes.
Therapy should be selected and individ-
•
ualised appropriately.
Overall, metformin is still the best choice
•
in respect of cardiovascular protection,
but the incretins may show benefits in
future.
Is type 2 diabetes really a CVD risk
equivalent?
Dr Hoosen Randeree, specialist physician and
endocrinologist in private practice, Durban
The increase in cardiovascular morbidity and
mortality associated with diabetes is well
established but ‘equivalence’ implies the
same future risk of CVD, with the practical
implication that intervention strategies
should yield similar benefits.
Answering the question is complicated by
the fact that different studies have different
endpoints as well as varying definitions of
coronary artery disease (CAD)/coronary heart
disease (CHD), blurring the associations
seen. Dr Randeree cited as an example the
fact that people living with diabetes have
a lower risk of future myocardial infarction
(MI) than individuals who have had a
previous MI. ‘Baseline risk depends on the
type of study and is much lower in large
population studies than in those evaluating
smaller, high-risk populations.’
Many determinants need to be taken into
account when looking at the relationship
between diabetes and CAD, including
regional differences, ethnicity, age threshold
for transition to high-risk status, age at
diagnosis and duration of diabetes, type of
diabetes therapy, risk factors, microvascular
disease, family history and dietary/lifestyle
habits. ‘There are many confounders in this
relationship, which is not a linear one’, he
said. ‘You therefore cannot call diabetes a
CVD risk equivalent.’
It was a 1998 article by Haffner
et al
.
1
that ‘started all the trouble’ by concluding
risk equivalence, even though many other
studies have shown this conclusion to be
wrong. ‘Although diabetes is a major risk
factor requiring aggressive treatment, a
blanket approach, irrespective of overall
risk may confer little benefit. Many factors
influence risk, so treatment therefore needs
to be individualised. We need to develop
a unique model that takes into account
diabetes-specific risk factors in order to
risk-stratify diabetics in future. Just as HbA
1c
targets are individualised, so too must we
differentiate patients in respect of future
CVD risk.’
1.
Haffner SM,
et al. N Engl J Med
1998;
339
: 229–
234.
Acute coronary syndrome in
diabetes: how do we improve
clinical outcomes?
Dr Sajidah Khan, principal specialist in
cardiology, Wentworth and Albert Luthuli
central hospitals, Durban
Acute coronary syndrome (ACS) indiabetics is
associatedwithhighermortalityrates,greater
morbidity and more co-morbid conditions.
‘Type2diabetes ismore thanhyperglycaemia.
The unified pathophysiology of oxidative
stress and subclinical inflammation drives
both diabetes and CVD, and diabetics have
Drug Trends
