CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 2, March 2012
AFRICA
117
African market’, he noted.
The defining characteristics of these
two classes of agents are the supra-phys-
iological levels of GLP-1s, attained by
exenatide or liraglutide treatment (the
GLP-1 agonists), and the physiologically
stable levels of GLP-1 attained by the use
of DPP-4 inhibitors. ‘The actions of the
injectable GLP-1 agonists are therefore
generally more powerful than the oral
DPP-4 inhibitors. The incretins’ enhance-
ment of glucose-induced insulin secre-
tion and the restoration of the glucagon-
suppression response are particularly rele-
vant, as glucagon is certainly the forgot-
ten hormone of type 2 diabetes’, he said.
Referring to exenatide (twice daily) and
the more powerful once-weekly dosage
not yet available in South Africa, and to
liraglutide (once daily), Dr Distiller noted
that their promise is partially fulfilled by
the fact that the reduction in HbA
1c
levels
(0.8–1% reduction depending on baseline
HbA
1c
level) is maintained over a two to
three-year period and there is a progres-
sive and probably meaningful weight loss.
‘There is considerable interest in
the non-glycaemic potential benefits of
GLP-1 agonists with regard to their neuro-
and cardioprotective effects. A real-life
study in medically insured patients, the
Life-Link study, has recently shown a
16% reduction in cardiovascular events in
patients on exenatide.’ Dr Distiller noted.
‘With regard to the ultimate promise
of these agents, the increased prolifera-
tion and reduced apoptosis 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
TZDs and basal insulin’. ‘At this juncture,
liraglutide 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 noted ‘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 suggestion that they preserve
β
-cell function. Overall, their cardiovas-
cular effects are not yet as well researched
as the GLP-1 agonists’, he noted.
With regard to when to use these
agents,
10
Dr Distiller noted that early use
when there is still
β
-cell function is taken
up in many algorithms as an alternative
for sulphonylureas with metformin. They
are also used in combination with insulin,
following acceptable trials and registration
for use of the particular agent with insulin.
As DPP-4 receptors are widespread
in the body, and despite the claimed
specificity of these inhibitors, Dr Distiller
noted a general acceptance that these
drugs have a subtle effect on the immuno-
surveillance system, leading to increased
incidence of bronchitis, for example.
With regard to the GLP-1 analogues
and their risk of pancreatitis, pancre-
atic and thyroid cancer, there is an alert
but not yet an alarm, despite the much-
commented article on post-marketing
surveillance’,
11
he concluded.
Is type 2 diabetes a cardiovascu-
lar risk equivalent?
Dr AD Horak, Dr Hoosen Randeree
A stimulating debate concluded the
presentations, with Dr AD Horak (Cape
Town) presenting the view that diabe-
tes is worse than a cardiovascular risk
equivalent, while Dr Hoosen Randeree
(Parklands Hospital, Durban) felt that
diabetes is less than a cardiovascular
risk equivalent because future risk is
confounded by the patient’s ethnicity, age,
gender and age of onset of diabetes. The
type of therapy used in the treatment of
type 2 diabetes also confounds the assess-
ment of the condition as a cardiovascular
risk equivalent.
The conclusion of the participants was
that the clinician needs to focus on those
diabetic patients who will benefit most
from preventative therapy, so as to reduce
the cardiovascular and vascular conse-
quences of type 2 diabetes.
Dr F Mohamed, J Aalbers
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Diabetic dyslipidaemia: new therapies
Prof Derick Raal
•
A typical diabetes lipogram: small, dense LDL-C, low HDL-C and high triglyc-
eride levels.
•
Statin’s main effect is reduction of LDL-C levels.
•
Fibrate’s main effect is reduction of triglyceride and increased HDL-C levels.
•
Niacin reduces triglyceride and raises HDL-C levels.
•
There is still a substantial residual risk of cardiovascular disease, even when the
LDL-C level has been greatly reduced.
•
Triglycerides: no clear cardiovascular risk (if one corrects for other factors).
FIELD and ACCORD LIPID trials showed no cardiovascular benefit with the
addition of fibrate to statin therapy.
•
HDL-C has multiple physiological functions. Low HDL-C levels have a clear
association with increased cardiovascular risk. New drugs target HDL-C.
•
Niacin raises HDL-C levels, decreases carotid intima–media thickness but does
not reduce cardiovascular events (AIM-HIGH study). Side effects are a problem.
•
Reconstituted high-density lipoprotein (rHDL) intravenous infusions can reverse
atheroma in the acute setting.
•
Cholesterylester transfer protein (CETP) inhibitors: torcetrapib raises HDL-C
levels, but increases death rate. New drugs in this class are being developed.
•
More aggressive lowering of LDL-C levels is still the best way of reducing
cardiovascular risk. One should aim for very low levels (
<
1.8 mmol/l in high-risk
patients). For every 2 mmol/l lowering of LDL-C levels, there is a 40% reduction
in cardiovascular event rate.
•
New therapy to lower LDL-C levels will soon be available as PSK9 inhibitors.
