CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012
AFRICA
291
increasing insulin dosages such as weight
gain, hypoglycaemia and complications
of high insulin dose therapy’, Prof Omar
said. He addressed firstly, the addition
of DPP-4 inbhibitors, vildagliptin and
sitagliptin to type 2 diabetes patients who
are poorly controlled on insulin.
16,17
‘The reductions in HbA
1c
levels
were modest, about 0.59%, but were
sustained over a year, when these agents
were added to patients on insulin, with
or without metformin. Experience
with hypoglycaemia was mixed, with
vildagliptin reducing hypoglycaemic
events and sitagliptin increasing these
events, perhaps due to the latter study
design, which tried to improve overall
glucose control. The weight reduction
effect was neutral in both studies’, Prof
Omar pointed out.
Turning to the incretin mimetics, Prof
Omar cited a proof-of-concept study
where the addition of exenatide to patients
on insulin glargine resulted in a greater
decrease in HbA
1c
level (a reduction of
1.9%), a low hypoglycaemic event rate
and weight loss of 1 to 2 kg in the
exenatide arm.
18
In a further study of exenatide, which
was given to patients with diabetes of
long duration (10 years) and an expected
low level of residual beta-cell function,
who were already on insulin, metformin
and pioglitazone, exenatide (bd) resulted
in improved glucose control accompanied
by a very significant reduction in insulin
(glargine) dose.
19
‘The adverse GI events
with incretin mimetics were as expected
but did improve over time’, Prof Omar
noted.
A newer concept: patients
already on liraglutide who are
then given added insulin
In a well-conducted study over a year,
20
the addition of insulin detemir to a group
of patients on metformin and liraglutide,
who were not yet at target HbA
1c
level,
was contrasted with the larger primary
group, which had reached optimal control
on these two agents (61% of the 988
patients), and to a control group within
the poorer-controlled arm without insulin.
The patients receiving insulin were told
to self-titrate, and in this well-controlled
therapy reached the recommended range
of 35–40 U/day of insulin detemir.
Importantly, the addition of insulin
detemir resulted in a further drop of 0.5%
in HbA
1c
level and patients did not gain
weight. The rate of hypoglycaemia was
very low at 0.23 in these insulin-treated
patients. ‘If you contrast this to the Treat-
To-Target study, where a rate of three to
3.5 episodes/patient year was seen, this
strategy was very successful’, Prof Omar
noted.
‘In conclusion, it is better to put
patients onto a GLP-1 agonist before
using insulin than using the reverse
strategy’, Dr Ajay Kumar.
Incretins and pancreatitis
Dr Adri Kok and Prof Juris Meier
This session scrutinised the evidence
related to the increased prevalence of
acute pancreatitis in type 2 diabetes
patients, acknowledging that these
patients have a three-fold higher risk of
developing pancreatitis (4.5 cases per
1 000 patient years). ‘We know that
the exocrine pancreas is also affected in
diabetic patients, with increased fibrosis
occuring in both type 1 and type 2
diabetes’, Dr Adri Kok noted.
Prof Meier presented the animal studies
on incretins and the risk of pancreatitis,
noting the difficulty of extrapolating
these findings to humans.
Following the published analysis
of the Adverse Event Reports (AERS)
as reported to the FDA,
21
the EASD
has recently published their expert
comment on their website
easd.org/easd/index.php/easd-statements.
Their evaluation indicates that at this
juncture the AERS evaluation cannot be
considered as robust data on which to
base clinical decisions.
Dr Kok concluded that physicians
should not over-interpret this matter, but
should be cautious. In summary, Prof
Ascott-Evans noted that there is no major
signal of concern about either incretin
mimetics or DDP-4 inhibitors and the
causation of pancreatitis.
Practical advice
Adding liraglutide therapy to a
sulphonylurea (SU) plus metformin
therapy, clinicians can halve the SU
dose and then monitor glucose levels
to decrease the risk of hypoglycaemia.
Hypoglycaemic events mark
vulnerability
Prof Brian Frier, honorary professor of
diabetes at the University of Edinburgh,
affiliated to the BHF Centre for
Cardiovascular Science.
‘Hypoglycaemia is a marker of a patient’s
vulnerability to a wide spectrum of
cardiovascular, cerebrovascular and
musculoskeletal events. It is not a transient
event, as commonly perceived. There are
longer-term effects on cardiac function,
platelets, the inflammatory response and
overall endothelial function’.
Expressing this view, Prof Brian Frier,
University of Edinburgh, drew on his
clinical insights gained from a research
career focused on the pathophysiology of
hypoglycaemia. While hypoglycaemia is
more common in type 1 diabetes patients,
type 2 diabetes patients on insulin
experience on average one severe event
per month.
‘In the definitive UK Hypoglycaemia
study,
22
we were surprised to see in a
real-world setting that hypoglycaemia
in type 2 diabetes patients treated
with sulphonylureas was higher than
we thought, at a rate of 7% per year.
Hypoglycaemic events also increased
over time in type 2 diabetes patients on
There have been no studies as yet using
incretin-based therapies in children/
adolescents under the age of 18 years
and clinicians should wait for these stud-
ies before treating this category of patient
–
Prof Juris Meier
When adding liraglutide to insulin-treated
patients, one can pragmatically reduce
the insulin units by 20–25%, and then
monitor
– Dr Mahomed AK Omar
‘There is no value in doing HOMA tests
prior to using these incretin-based thera-
pies, as they have been shown to be
effective across the diabetes spectrum
–
Prof Juris Meier
