DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
86
VOLUME 7 NUMBER 2 • JUNE 2010
triglycerides
•
<
7 mmol/l.
He added the rider that the LDL cholesterol
level should be even lower;
<
1.8 mmol/l in
those at especially high risk, for example when
there is established vascular disease.
Turning to hypertension, he underscored
that the UKPDS has shown clear benefits for
good blood pressure control with ACEs and
ARBs. It reduces the patient’s decline, as well
as the progression of retinopathy. A target of
130/80 mmHg is recommended.
Obesity in a diabetic seriously compounds
the risk of various complications, especially car-
diovascular disease. ‘Visceral fat is bad news’,
said Dr Randeree, ‘and “diabesity” is associ-
ated with a seven-fold greater risk of death
than diabetes alone. Weight loss is therefore
very important – and the more loss, the greater
the risk reduction.’ He did, however, point out
the irony that many treatments for diabetes
were associated with weight gain, making
obesity a particular challenge in diabetics.
Smoking, like obesity, contributes signifi-
cantly to a multiplication of risk and needs to
be discouraged.
Dr Randeree concluded that there is a ther-
apeutic gap that needs to be bridged, and that
effective diabetes treatment requires multifac-
torial interventions that go beyond glycaemic
control. ‘We need to be more aware of these
parameters, measure them regularly, respond
to our findings and treat aggressively enough
to make a difference.’
Optimising oral antidiabetic medication
Prof Willie Mollentze, Department of Medicine,
University of the Free State
According to NHANES data, worldwide, the
number of diabetic patients achieving blood
pressure and glycaemic targets is low – and
South Africa is probably doing worse than the
developed world. ‘We’re also failing dismally
when it comes to diabetic dyslipidaemia’, said
Prof Willie Mollentze, head of the Depart-
ment of Medicine at the University of the Free
State.
Prof Mollentze cites a number of reasons for
this. ‘Diet and lifestyle measures are often inef-
fective; none of the pharmacological options
currently available is ideal; management tends
to be too conservative; and patient compliance
is often poor. In addition, we’re dealing with
an underlying pathophysiology that entails the
relentless progression of beta-cell failure. Our
sub-optimal healthcare system adds yet more
barriers to effective treatment.’
He feels that diabetes cannot be treated in
isolation and that a new paradigm is therefore
needed. This entails a move away from the
conservative stepwise approach that is cur-
rently the norm. With this approach, there is
often a long delay before the introduction of
oral antidiabetic agents or insulin, with the
result that valuable time is lost and the patient
is at greater risk of developing complications.
There are also often delays in stepping up from
monotherapy to combination therapy.
‘Even short periods of hyperglycaemia
increase the risk of complications, so we need
to reach goals much sooner’, said Prof Mol-
lentze. ‘However, we still don’t have the ideal
agent that will normalise blood glucose, with
minimal side effects, while preventing macro-
and microvascular complications.’
The IDF global partnership’s new paradigm
marks a shift from conservative to aggressive
treatment – with an oral antidiabetic agent
introduced at diagnosis, along with lifestyle
measures. ‘We need to reach goals much
sooner’, said Prof Mollentze. The current
SEMDSA guidelines support this trend, recom-
mending lifestyle interventions plus metformin
at diagnosis as the first step in treating type 2
diabetes.
‘Lifestyle changes can be effective in
improving diabetes control and cardiovascular
risk, while reducing the use of medicine, but
long-term success is limited, hence the recom-
mendation of metformin. The maximum effec-
tive dose is 1 000 mg twice daily, but often 850
mg is sufficient and up-titration may be associ-
ated with side effects and reduced compliance,
while not providing additional benefit.’
One in five patients fail on metformin
monotherapy. The addition of glibenclamide is
indicated in these patients because of its syn-
ergistic effects with metformin.
Step 2 recommends the introduction of a
sulphonylurea or a basal insulin or pioglitazone
(although the latter is not the preferred option).
‘It’s important to start at low doses, given these
agents’ tendency to promote weight gain and
induce hypoglycaemia. Continuing metformin
therapy after the introduction of NPH insulin
helps to address these concerns, while also
providing superior glucose control.
Patients who self-monitor regularly have
been shown to reduce their HbA
1c
and con-
sequently reduce their macrovascular risk by
14%. Prof Mollentze cautioned, however, that
there is still a lack of consensus on the value
of this and no study data on optimal testing
frequency. ‘However, common sense suggests
that patients should indeed self-monitor.’
Prof Mollentze summed up with 10 steps
that should be followed in treating type 2 dia-
betics:
aim for good glycaemic control
•
monitor HbA
•
1c
every three months
manage dyslipidaemia, hyperglycaemia and
•
hypertension aggressively
refer newly diagnosed patients to special-
•
ist units
address underlying pathophysiology
•
treat aggressively to achieve HbA
•
1c
targets
within six months
if target is not reached at three months,
•
consider combination therapy
combination therapy should be introduced
•
sooner rather than later
when it comes to combinations of oral anti-
•
diabetic agents, use ones with complemen-
tary mechanisms
it is important to involve a multidisciplinary
•
team in the patient’s care.
A primer of insulin therapy – when, why
and how?
Prof MAK Omar, Durban
With time, oral antidiabetic agents stop work-
ing and diabetes control worsens as insulin
secretion drops and beta-cell failure progresses.
‘Insulin sensitivity declines too’, said Prof MAK
Omar, formerly of the Diabetes and Endo-
crinology Unit at the University of KwaZulu-
Natal and now in private practice.
He posed the question, ‘Why is insulin usu-
ally introduced later?’ While patient resistance
is an obvious answer, Prof Omar pointed out
that physician resistance and inertia should not
be discounted either. ‘Despite poor glucose
control and non-response to oral diabetics,
many doctors still follow the recommendation
of the DAWN study not to introduce insulin
“until absolutely essential”’, he said. ‘But one
should not delay, as insulin may be a saviour in
terms of preventing complications.’
Prof Omar noted that there are four pos-
sible regimens:
bedtime basal insulin combined with oral
•
antidiabetics
biphasic insulin twice daily
•
a basal/bolus regimen
•
an insulin pump.
•
Option one works best when fasting glucose is
high – and the analogues are preferable to NPH
because they’re relatively ‘peakless’, ensuring a
consistent level during the day. They also have
the advantage of once-daily dosing, a lower
risk of hypoglycaemia and a safety profile com-
parable to that of NPH.
Biphasic insulin may be required if this
approach does not work, and if that still doesn’t
bring patients to target, a basal/bolus regimen
may be required to suppress hepatic function
at night and normalise post-prandial glucose
levels. Prof Omar underscored that numerous
analyses have refuted earlier findings that the
basal insulin analogue, glargine, is associated
with an increased risk of malignancy. Doctors
therefore have no reason not to prescribe it.
‘With insulin, the sky’s the limit, and we can
drop HbA
1c
as low as we wish. So don’t delay.
Which regimen is chosen should be individual-
ised to the patient in question.
continued on page 88
