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The ABCD nationwide exenatide audit
About the ABCD nationwide
exenatide audit
It is not easy to appreciate, looking back, the enthusiasm which greeted
the arrival, in 2007, of exenatide as an agent which could be prescribed in the UK. For the first time we had an agent which both improved HbA1c
and reduced weight. This was highlighted in the
head to head study of exenatide against insulin glargine in which both agents reduced HbA1c by
the same amount, though
glargine caused weight increase while exenatide led to weight loss.
By 2008 some clinical experience with exenatide had been gained by most
diabetologists since its launch in the UK in 2007. ABCD realised that it
was in a unique position to accelerate understanding of this new agent
by pooling all the individual experiences of its many members through a
national audit.
ABCD had already undertaken several, relatively small, nationwide audits,
and now realised that the experience gained could be scaled up,
especially given the widespread enthusiasm amongst its members for the
new agent. ABCD considered
(2008) what might we learn from such a national audit and set up a
questionnaire on a password protected subweb of its Sharepoint website
for collection of anonymised patient data.
The nationwide audit was launched on 12th December 2008
and a call was sent out for data to be submitted by a deadline of 18th
February 2009, with
a regular countdown email sent out to all ABCD
members. It is testament to the enthusiasm of clinicians for exenatide
that over those two months data was submitted on 5313 patients with
usable data on 3913. The first data analysis was presented by Chris
Walton at a
DUK
satellite symposium in Glasgow on 10th March 2009 with further analysis
presented by Bob Ryder at the
Spring ABCD
meeting in Bristol on 8th May 2009. The data continued to accumulate
until the last deadline for data submission on 20th July 2009. By that
time, only 7 months after launch, the audit had collected anonymised data on 6717 patients
(2007-2009) submitted by 315 contributors from 126 centres. The data was
presented at the
Spring ABCD meeting in Newcastle on 7th May 2010. As well as
nine published papers, there have also been
17 published abstracts,
12 oral presentations and
13 poster presentations.
What we learned from the exenatide
and liraglutide audits
After the audit had been active for 5 years, at the ABCD autumn meeting
in 2014, Bob Ryder summarised the main findings from the ABCD nationwide
exenatide and liraglutide audits and
the slides from that presentation
are available for viewing. In summary, the findings over the 10 years
since the audit was launched have been:
The patients treated with exenatide or liraglutide in real clinical practice are much
heavier and with much poorer glycaemic control than in clinical trials
of these agents; nevertheless, the agents have proven to be very
effective.1
Exenatide and liraglutide were used outside NICE guidelines in
substantial numbers of patients and were found to be effective in
outside NICE guidelines. In particular, the agents were used with
insulin (40% in the nationwide liraglutide audit) with good effect in
many patient.2
Off licence use of exenatide with insulin was found to be
safe and effective in real clinical practice, a reduction in insulin
dose frequently occurred, weight fell and 1 in 6 patients were able to
come off insulin.3,4
An important safety issue was uncovered in that some clinicians
attempted to stop insulin when starting exenatide in order to stay
within license. This led to harm to the patient in some instances - for
example there are 11 reported cases of ketosis or diabetic ketoacidosis
- 7 of these occurred to patients who stopped insulin at the time of
exenatide initiation. Analysis of audit data allowed us to recommend
that when starting exenatide in an insulin-treated patient, not to stop
the insulin but rather to tail the insulin off during treatment if
response to treatment allowed.5,6
When concerns were raised in 2013 in a TV documentary and in the
British Medical Journal that incretin therapies might cause pancreatic
damage, we were able to publish data suggesting that in the ABCD audits
there is no evidence of such a side effect and that most cases of acute
pancreatitis in the ABCD exenatide and liraglutide audits had other
causes for acute pancreatitis, in particular gall bladder disease.7,8,9,10,11
Many patients with a professional drivers licence who would lose
their jobs if they went onto insulin, were able to avoid insulin, and
maintain similar glycaemic outcomes and keep their jobs by using
exenatide or liraglutide.12,13
Liraglutide was found to be safe and effective among patients with
moderate renal impairment, even though that was an exclusion for use at
the time.14,15
Liraglutide use was found to be associated with a reduction in alanine
aminotransferase levels (an index of fat in the liver) when they are
elevated.16
Though initially liraglutide was not licensed for use with insulin and
in due course it was licensed only for use with insulin determir, it was
found in the audit to be effective with all the common insulin regimes,
whether basal, basal-bolus or biphasic.17
Exenatide and liraglutide may be less effective at improving glycaemic
control amongst non-insulin treated South Asians.18
Long duration of diabetes and insulin use both predict reduced
response to liraglutide, with insulin use being the strongest predictor.19
Improvements in HbA1c and weight were seen when switching from
exenatide and DPP4 inhibitors to liraglutide.20
Older age and non-metformin use were associated with more significant
gastro-intestinal side effects leading to discontinuation of liraglutide
treatment.21,22
In occasional exenatide treated patients, the nausea, vomiting or diarrhoea was so severe
that they developed transient acute kidney injury. No other new safety
issues were uncovered.23,24
Starting liraglutide was found to reduce 10-year cardiovascular risk
as assessed by the UKPDS risk-engine.25
Further
information
Further enquiries may be made to the ABCD nationwide audits
database administrator of the project,
Melissa Cull |
Exenatide audit - what might we learn? - 2008
A4 Summary sheet about the audit - 2008
Exenatide audit questionnaire - 2008
Data collection proforma for use in clinic - 2008
Nationwide liraglutide audit
Papers, abstracts, presentations, posters from the audit
Further
information- contact us
Main ABCD homepage
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