DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
116
VOLUME 10 NUMBER 3 • SEPTEMBER 2013
treatment that lowers both blood glucose
levels and weight, while also being safe in
respect of another important component of
diabetes, namely hypoglycaemia.
Hypoglycaemia and cardiovascular
outcomes in diabetes
Prof Wolfgang Schmidt, chief of GI/
Hepatology and Diabetes Services and
director of the Department of Medicine,
St Josef-Hospital, Ruhr-University Medical
School, Bochum, Germany
Hypoglycaemia is an important confounder
in the management of diabetes, and gly-
caemic control is only a part of the story. To
achieve an overall favourable outcome also
requires control of CVD risk factors and an
avoidance of weight gain and hypoglycae-
mic episodes.
Multiple studies have shown the ben-
efits of good early glycaemic control and its
association with a lower CHD event rate. Its
legacy effect confers significant benefit 10
to 15 years later. The challenge in achiev-
ing this favourable scenario lies in attaining
glycaemic control, lowering lipid levels and
blood pressure and avoiding hypoglycaemia
while not doing harm. Intensive intervention
in diabetes and better glycaemic control
often come at the price of increased weight
gain and more hypoglycaemic episodes,
which is a bad risk–benefit ratio. Certain
patients are at particular risk, including the
elderly, those with diabetes of longer dura-
tion and/or a high baseline HbA
1c
level, and
patients with renal dysfunction or peripheral
neuropathy.
Severe hypoglycaemic events are associ-
ated with a 2.5% higher mortality rate so
therapy-induced hypoglycaemia must be
avoided. ‘Why is it so dangerous?’ asked
Prof Schmidt. ‘It has pro-arrhythmic effects,
is associated with cognitive dysfunction
and delayed recovery in the elderly and is
both pro-thrombotic and pro-inflamma-
tory. In addition it causes increased anxiety
in patients, which in turn has a negative
impact on compliance.’ So control needs to
be both stringent and safe from the time of
diagnosis.
‘In 2013, when managing diabetes, we
need to avoid hypoglycaemia, especially in
those with cardiovascular risk, avoid weight
gain, and reconstitute beta-cell function and
stop their loss. Is GLP-1 incretin therapy an
option?’
Prof Schmidt feels strongly that it is.
‘GLP-1 normalises glucose levels in poorly
controlled patients, without causing
hypoglycaemia. Liraglutide improves first-
phase insulin secretion and maximal beta-
cell insulin capacity. Importantly, it does
not induce insulin secretion when glucose
levels are low. Used in combination with
metformin, the risk of hypoglycaemia is low,
comparable with that of placebo. It also
improves biomarkers of CVD risk, notably
reducing systolic blood pressure.’
Liraglutide therefore has a favourable
impact on the composite endpoint of opti-
mal HbA
1c
concentrations, weight loss and
hypoglycaemia. ‘It shows great promise in
helping us get our patients to their individu-
alised HbA
1c
targets early, without weight
gain and hypoglycaemia, while preserving
beta-cell function,’ Prof Schmidt concluded.
P Wagenaar
