46 / 56
DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
44
VOLUME 13 NUMBER 1 • JULY 2016
Drug Trends in Diabetes
I
n type 2 diabetes, careful control of blood
glucose can help prevent or delay micro- and
macrovascular complications. Initially this may
be adequately achieved with lifestyle changes
and oral medication, but because of the
progressivenatureofdiabetes,characterisedby
gradual decline in
β
-cell function and density,
most patients will eventually require insulin
to achieve glycaemic goals.
1
The benefits of
control achieved early in the disease remain
for many years, despite it becoming more
difficult to maintain target glucose levels.
2
Hypoglycaemia limits effective
diabetes management
A common limitation in achieving glucose
targets however, bothwith oral therapies and
especially as one intensifies insulin therapy,
is hypoglycaemia.
3
Hypoglycaemia not only
has a negative impact on the wellbeing of
the patient in the short and long term, it is
also an important factor underlying clinical
inertia. This describes both a reluctance by
clinicians to intensify therapy in patients
who are insufficiently controlled on current
therapies and a decreased motivation in
patients to adhere to prescribed therapies.
3
Hypoglycaemia becomes more
common with duration of therapy
Althoughhypoglycaemiaisinfrequentinearly
type 2 diabetes, the duration of diabetes, loss
of the glucagon response to hypoglycaemia,
and duration of insulin therapy cause the
incidence to begin to increase, approaching
that of hypoglycaemia in type 1 diabetes.
Mild hypoglycaemic events are even more
common, but less reported. One prospective
study reported that patients with type 2
diabetes were experiencing more than 16
mild hypoglycaemic episodes per year!
4
Nocturnal hypoglycaemia is especially
common. Asymptomatic hypoglycaemia may
be identified with continuous glucose moni-
toring in around 50% of patients with type 2
diabetes, and the majority of episodes (74%)
occur at night.
5
Nocturnal hypoglycaemiamay
be suspected in patients who report morning
headache, poor quality of sleep, vivid dreams
or nightmares and profuse sweating in bed.
Restlessness during sleep may disturb the
partner.
6
Hypoglycaemia in type 2 diabetes increases the risk of cardiovascular events
Hypoglycaemia worsens an already
increased risk of CVD
Patients with type 2 diabetes are at
increased risk of cardiovascular disease
(CVD). However, results of long-term
studies of intensive glucose-lowering for
CVD prevention have been disappointing.
Tighter glycaemic control appears to be
no more effective than standard glucose
reductions in reducing the risk of CVD
mortality among high-risk individuals.
One hypothesis that might help to
explain these observations is the occurrence
of severe hypoglycaemic episodes with
intensive therapy. It has been suggested
that severe hypoglycaemia is associated
with a significantly increased risk of adverse
vascular events and CVD mortality.
7
There are various mechanisms that
link hypoglycaemia to increased risk of
myocardial ischaemia, acute thrombotic
events and accelerated atherosclerosis,
especially in an individual who is already at
high risk of CVD. Hypoglycaemia induces
a number of adverse acute haemodynamic
changes, including tachycardia, systolic
hypertension, elevated cardiac output
and myocardial oxygen demand, and
increases the risk of potentially fatal
cardiac arrhythmias. It is also associated
with pro-thrombotic and pro-inflammatory
effects, such as increased neutrophil
and platelet activation, increased levels
of factor VII, C-reactive protein, vascular
endothelial growth factor (VEGF) and
inflammatory mediators, and reduced
vasodilatation consequent to endothelial
dysfunction.
7
Clinical implications of treatment-
related hypoglycaemia
From a clinical perspective, while it is
important to achieve adequate glycaemic
control, it is also desirable to avoid
hypoglycaemia, especially in patients who
are at high risk for CVD.
7
Patients who are
especially at risk include those with:
3
older age
•
longer duration of diabetes
•
concomitant medication
•
renal dysfunction
•
hypoglycaemia unawareness
•
cognitive dysfunction
•
peripheral neuropathy
•
intense glucose-lowering strategy.
•
Patients and relatives require education
on the symptoms of and risk factors for
hypoglycaemia, and appropriate manage-
ment, should it occur.
3
Where appropriate,
it would be prudent to consider therapies
with a lower propensity to hypoglycaemia.
Where insulin is required, it needs to be
titrated carefully.
New insulins provide solutions to
better diabetes management
Modern insulins carry a lower risk of
hypoglycaemia than older insulins.
3
Furthermore, progress in insulin therapy
continues, allowing improved glycaemic
control with fewer injections and less chance
of hypoglycaemia, especially at night.
8
Leading these developments, Novo Nordisk
aims to make better diabetes outcomes
available to all patients because achieving
target glycaemic control should not be at
the expense of adverse outcomes, which
can be a direct result of therapy.
1. Henske JA, Griffith ML, Fowler MJ. Initiating and
titrating insulin in patients with type 2 diabetes.
Clin Diab
2009;
27
(2): 72–76.
2. Holman RR, Paul SK, Bethel MA,
et al
. 10-year
follow-up of intensive glucose control in type 2
diabetes.
N Engl J Med
2008;
359
: 1577–1589.
3. Ahren B. Avoiding hypoglycaemia: a key to success
for glucose-lowering therapy in type 2 diabetes.
Vasc Health Risk Manag
2013;
9
: 155–163.
4. Desouza CV, Bolli GB, Fonseca V. Hypoglycemia,
diabetes, and cardiovascular events.
Diabetes Care
2010;
33
(6): 1389–1394.
5. Chico A, Vidal-Ríos P, Subirá M, Novials A. The
continuous glucose monitoring system is useful for
detecting unrecognized hypoglycemias in patients
with type 1 and type 2 diabetes but is not better
than frequent capillary glucose measurements for
improving metabolic control.
Diabetes Care
2003;
26
(4): 1153–1157.
6. Frier BM. How hypoglycaemia can affect the life of
a person with diabetes.
Diab Metab Res Rev
2008;
24
: 87–92.
7. Kilov G. Hypoglycaemia and cardiovascular risk in
people with type 2 diabetes.
Diabetes Prim Care
Australia
2016;
1
: 33–35.
8. Cooper JG, Pieber TR, Cariou B,
et al
. Treatment
intensification with IDegAsp BID vs IDeg OD
plus IAsp in insulin-treated patients with type 2
diabetes: a randomised, controlled phase 3 trial.
Diabetologia
2014;
57
(Suppl 1): S69.