VOLUME 7 NUMBER 4 • NOVEMBER 2010
169
SA JOURNAL OF DIABETES & VASCULAR DISEASE
EASD WATCH
with diabetes at an older age, patients
who had a higher HbA
1c
at the time of the
sensor use, and patients who used their
sensor more often.
The overall positive finding was that
sensor-augmented pump therapy com-
pared to multiple daily injections signifi-
cantly improved HbA
1c
values without an
increased risk of hypoglycaemia.
ADDITION study provides impetus
to GP-based diabetes screening and
management
The aims of the ADDITION study, the
Anglo–Danish–Dutch study on intensive
treatment in people with screen-detected
diabetes in primary care were three-fold:
first, to assess the feasibility of screening
for diabetes in large populations, second,
the feasibility and effectiveness of imple-
menting multifactorial cardiovascular inter-
vention strategies in patients diagnosed
with diabetes, and third, assessing five-year
cardiovascular outcome data in the treat-
ment group.
This study was very similar to the STENO
studies, which examined multifactorial
intervention in patients with established
cardiovascular risk factors, most of which
had been present for a long period of time.
The difference between the STENO and
ADDITION studies was that the latter study
enrolled patients in whom the diabetes
was newly diagnosed during population
screening in at-risk groups, and interven-
tion started early in the course of diabetes.
The primary outcome of the ADDITION
trial, the decrease in cardiovascular ben-
efits, was negative, which could be inter-
preted as saying that the trial as a whole
was negative. However, there were some
important positive findings from this trial.
The first was that population-based
screening is both possible and effective in
detecting early diabetes. Secondly, the trial
showed that intensive multifactorial inter-
vention, including targeting HbA
1c
levels of
6.5% in these patients with newly diag-
nosed screen-detected diabetes was safe,
with no excess cardiovascular mortality, as
seen in the ACCORD trial.
Possible explanations for the apparent
negative outcome of the cardiovascular
benefit, i.e. that there was no significant
benefit, came from the fact that treatment
in the conventional arm improved signifi-
cantly during the trial in accordance with
regional guidelines, resulting in only very
small differences in blood pressure, cho-
lesterol and glycaemic control between
the two groups. It is possible that had the
patients been followed up for longer, the
results may indeed have been positive.
The final positive outcome of this trial
was that this was a population-based gen-
eral practitioner trial, which showed that
firstly, screening for diabetes is possible at
a general practitioner level, and secondly,
intensive multifactorial intervention to
reduce cardiovascular risk is easily applica-
ble, again at a general practitioner level.
Incretin-based therapies
A session of major interest was new devel-
opments in incretin-based therapies. The
first was a trial studying exenatide added to
insulin glargine-treated patients with type
2 diabetes. This was a double-blind, pla-
cebo-controlled trial of 259 patients with
a mean age of 59 years, a mean weight of
94 kg, a mean HbA
1c
value of 8.4%, and
a diabetes duration of 12 years, using an
average insulin dose of 48 units.
These patients were randomised to
either exenatide or placebo while con-
tinuing with insulin glargine treatment.
The addition of exenatide improved HbA
1c
levels without significantly increasing hypo-
glycaemia. This was predominantly driven
by an improvement in the prandial glucose
levels and is an important step in confirm-
ing the additional benefit of adding GLP I
analogues to insulin-based therapy, some-
thing which is already widely done off label
by many practitioners.
A second and similar study reviewed
the clinical notes and laboratory studies of
doctors initiating exenatide treatment after
its introduction in diabetic patients in the
United Kingdom: the ABCD audit. Here
they analysed the decisions the diabetolo-
gists made, either to stop insulin therapy,
as recommended in the package insert,
or whether insulin therapy was continued
with the addition of exenatide; in other
words off-label use of exenatide.
The results of this study showed that
continuing insulin therapy at the time of
exenatide initiation was safe and resulted
in improvements in HbA
1c
levels and weight
reduction. Where insulin was stopped com-
pletely at initiation of exenatide, almost
half the patients had worsened glycaemic
control. This suggests that it is safe to con-
tinue insulin treatment in patients being
initiated on exenatide, although possibly at
a slightly reduced dose.
The next study in incretin-based thera-
pies was a new GLP I analogue called
taspoglutide, which was a once-weekly
treatment and this was compared in a
phase III trial with twice-daily exenatide.
Taspoglutide showed small but clinically
significant improvements in glycaemic con-
trol with similar weight reduction and simi-
lar tolerability, although there was slightly
increased incidence of gastrointestinal side
effects. These, however, did not reach clini-
cal significance.
The following study was a retrospective
cohort study on the risk of acute pancreati-
tis in patients who were initiated on either
exenatide or other antidiabetic drugs,
using two commercial US health insurance
claim databases. The outcome of this was
reassuring in that it showed no significant
increase in pancreatitis when exenatide
was used.
The next study assessed the efficacy of
sitagliptin on glucose control in patients
with type I diabetes. This was a pilot study
and they found in this group of patients
that sitagliptin reduced the total daily insu-
lin dose needed, and reduced the HbA
1c
and mean blood glucose values in patients
with type II diabetes. It was suggested that
further studies should be undertaken to
determine the efficacy and safety of sitag-
liptin in patients with type I diabetes.
The final update on the incretin-based
therapies was evaluating an implantable
device, which is slightly smaller than a
matchstick and supplies a continuous and
consistent delivery of exenatide using a
subcutaneous osmotic delivery system. This
can last for up to 12 months with single
administration.
This was a phase II study to evaluate the
efficacy, safety and tolerability of this treat-
ment and was compared with the normal
twice-daily exenatide injections in patients
previously treated with only metformin.
The ITCA 650 device ensures 100%
compliance for the long-term treatment
of diabetes and resulted in substantial
changes in HbA
1c
levels and weight with-
out the need for repeated injections. This
will no doubt lead to further phase III and
larger clinical trials looking at efficacy and
safety.
Late breaking news on the two
clinical trials: NAVIGATOR and
LEAD studies
The NAVIGATOR trial studied nateglinide in
the treatment of early diabetes, assessing
the incidence of diabetes and core cardio-
