Original article

Cost and effectiveness of exenatide combined

with insulin, compared to exenatide
combined with oral hypoglycaemic agents
Dr Sarika Deshpande
MBBS, BSc(Hons), MRCP, Specialist Registrar,
Endocrinology, West Suffolk Hospital, Bury St
Edmunds, UK
Dr John DA Clark
MA, MD, FRCP, Consultant Endocrinologist, West
Suffolk Hospital, Bury St Edmunds, UK
Correspondence to: Dr JDA Clark, Consultant
Endocrinologist, West Suffolk Hospital, Bury St
Edmunds, Suffolk IP33 2QZ, UK;
email: John.Clark@wsh.nhs.uk
Received: 15 July 2011
Accepted in revised form: 19 September 2011
Abstract
There have been few studies investigating the use of GLP-1 agonists in patients with
insulin-treated type 2 diabetes and none looking at the costing. We compared the efficacy and
relative cost of adding exenatide treatment to patients with type 2 diabetes receiving either
oral hypoglycaemic agents (OHAs) or insulin.
Patients were recruited from West Suffolk Hospital Diabetes Centre. Data were acquired
retrospectively from 207 patients completing six months of treatment.
Of 207 patients, 188 demonstrated good clinical progress with a mean HbA1c reduction of
1.6% (p<0.0001) and weight loss of 6.9kg (p<0.0001). Nineteen patients discontinued
exenatide as HbA1c reduction did not achieve the NICE target (0.4%; p=0.29), but they did
achieve significant weight loss (5.6kg; p<0.0001). The 188 patients continuing on exenatide
were sub-divided into insulin-treated (n=88) or tablet-treated (n=100). At six months,
tablet-treated patients achieved an HbA1c reduction of 1.6% (p<0.0001) and weight loss of
6.5kg (p<0.0001). Insulin-treated patients achieved similar results: HbA1c reduction 1.6%
(p<0.0001), weight loss 7.3kg (p<0.0001). After six months of exenatide treatment, the mean
reduction in daily insulin dose was 48 units/person in the insulin-treated group. In the
tablet-treated group, the cost of diabetic medication (per person/month) after six months was
£54.90 above baseline, whereas in the insulin-treated group this was only £36.20 above
baseline, because the reduction in insulin dose offset the cost of exenatide.
It was concluded that exenatide is clinically effective in both insulin-treated and
tablet-treated type 2 diabetes, but is more cost effective in those originally treated with
insulin. Copyright © 2011 John Wiley & Sons.
Practical Diabetes 2011; 28(9): 390–393

Key words
exenatide; insulin; GLP-1 agonist; cost effective

Introduction treatment in patients with insulin-

Exenatide has been available for the
treatment of type 2 diabetes since
2007 in the UK,1 having been ini-
tially launched in the USA in 2005.2
The National Institute for Health
and Clinical Excellence (NICE) pro-
vided guidance on its role in 20083
and updated it in 2009,4 with slightly
broader criteria for its use.
The NICE guidance recom-
mends use of exenatide in patients
with a body mass index (BMI)
≥35kg/m2, with significant physical
or psychological morbidity and
an HbA1c >7.5% (58mmol/mol)
despite treatment with oral hypogly-
caemic medication. NICE recom-
mends continuation of exenatide
after a six-month trial, if a reduction
of HbA1c by 1% and weight loss of
3% are achieved.
Although not included in the
manufacturer’s licence, many clini-
cians are commencing exenatide
treated type 2 diabetes. A recent
national survey of exenatide treat-
ment in the UK recorded that of
6717 patients known to be treated
with exenatide 36.7% were also
receiving insulin.5–7
We have had access to treatment
with exenatide since May 2008 and
have had support from our primary
care trust to use it in patients with
tablet-treated or insulin-treated type
2 diabetes. In this study, we compare
the efficacy and relative cost of treat-
ment with exenatide in these two
groups of patients.
Patients and methods
The study is a retrospective analysis
of patients recruited from the West
Suffolk Hospital Diabetes Centre.
All gave informed consent. In our
practice, patients with type 2 dia-
betes were selected for treatment
with exenatide if they were receiving

390 PRACTICAL DIABETES VOL. 28 NO. 9 COPYRIGHT © 2011 JOHN WILEY & SONS
 Original article
Cost and effectiveness of exenatide combined with insulin vs exenatide combined with OHAs

oral hypoglycaemic agents (OHAs)

Patients continuing exenatide at 6 months (n=188)
and fulfilled NICE criteria.3 In addi-
tion, type 2 diabetes patients who
HbA1c (%) Weight (kg) BMI
met the criteria but were already
receiving treatment with insulin
Baseline 9.7±1.5 120.0±21.6 41.6±7.3
were also offered therapy with exe-
(CI: 8.2 to 11.2) (CI: 98.4 to 141.6) (CI: 34.3 to 48.9)
natide. These patients had been
treated with insulin due to poor con-
Change at 6 months -1.6±1.6 -6.9±5.4 -2.4±1.9
trol with OHAs alone, but were still
(CI: -3.2 to 0) (CI: -12.3 to -1.5) (CI: -4.3 to -0.5)
unable to optimise glucose control
and weight.
P-value (vs baseline) p<0.0001 p<0.0001 p<0.0001
Our study population included
all patients completing six months of
Patients discontinuing exenatide at 6 months (n=19)
treatment. Data were acquired from
the six-month review. All patients HbA1c (%) Weight (kg) BMI
commenced on exenatide were
initiated and followed up by the hos- Baseline 9.1±1.6 126.6±19.1 42.8±6.9
pital diabetes specialist nurse team. (CI: 7.5 to 10.7) (CI: 107.5 to 145.7) (CI: 35.9 to 46.7)
Reviews were performed at one
month and three months post initia- Change at 6 months -0.4±1.5 -5.6±4.4 -1.9±1.6
tion prior to the six-month review. In (CI: -1.9 to 1.1) (CI: -10.0 to -1.2) (CI: -3.5 to -0.3)
addition to medication dose titra-
tion, patients were supported with P-value (vs baseline) p=0.29 p<0.0001 p=0.01
dietary and lifestyle advice.
The OHAs used by patients Table 1. Results after 6 months of exenatide (values are presented as means ± SD)
included combinations of met-
formin, sulphonylureas, thiazolidine-
diones, and dipeptidyl peptidase-4 Total (n=188) with Total (n=19) failed P-value
inhibitors. In the majority of cases, success at 6 months at 6 months
the metformin dose was maintained, Male, n (%) 108 (57%) 13 (68%) –
sulphonylureas were reduced or
withdrawn, and thiazolidinediones Female, n (%) 80 (43%) 6 (32%) –
and dipeptidyl peptidase-4 inhibitors
were discontinued. Age, years 57.4±10.0 58.2 ±11.7 p=0.74
Of 312 patients commenced on (CI: 47.4 to 67.4) (CI: 46.5 to 69.9)
exenatide since May 2008, 207 had
completed their six-month review at Diabetes duration, years 10.0±6.7 12.7±7.5 p=0.09
the time of this analysis. A further 40 (CI: 3.3 to 16.7) (CI: 5.2 to 20.2)
patients had been started on exe-
natide more than six months previ- Baseline HbA1c, % 9.7±1.5 9.1±1.6 p=0.2
ously but had discontinued exenatide (CI: 8.2 to 11.2) (CI: 7.5 to 10.7)
prior to the six-month review. Thirty-
seven had discontinued due to side Baseline weight, kg 120.0±21.6 126.6±19.1 p=0.2
effects, one patient had moved out of (CI: 98.4 to 141.6) (CI: 107.5 to 145.7)
the area, and two had died from
established ischaemic heart disease. Baseline BMI, kg/m2 41.6±7.3 42.8±6.9 p=0.5
Our analysis is of the 207 patients (CI: 34.3 to 48.9) (CI: 35.9 to 49.7)
who completed at least six months of
treatment with exenatide. Table 2. Baseline characteristics of 207 patients completing 6 months of exenatide treatment (values
Data were obtained retrospec- are presented as means ± SD)
tively from the West Suffolk Hospital
diabetes database. Costs of medica- with this treatment as they were 2.4±1.9kg/m2 (p<0.0001). (Table 1.)
tions were calculated using prices judged to be having a good clinical In comparison, the group that dis-
from the British National Formulary response. The remaining 19 patients continued exenatide at six months
(Edition 61). Statistical analysis was discontinued exenatide therapy. failed to improve their diabetic con-
carried out using the t-test score. The group continuing exenatide trol with a non-significant mean
treatment recorded significant HbA1c reduction of 0.4±1.5%
Results improvements in HbA1c, weight and (p=0.29), but they did achieve a
A total of 207 patients had completed BMI, achieving a mean reduction significant reduction in weight, los-
six months of treatment with exe- in HbA1c of 1.6±1.6% (p<0.0001), ing a mean of 5.6±4.4kg (p<0.0001)
natide and, after review by clinicians, mean weight loss of 6.9±5.4kg and a mean BMI reduction of
188 patients were advised to continue (p<0.0001), and BMI reduction of 1.9±1.6kg/m2 (p=0.01). (Table 1.)

PRACTICAL DIABETES VOL. 28 NO. 9 COPYRIGHT © 2011 JOHN WILEY & SONS 391
Original article
Cost and effectiveness of exenatide combined with insulin vs exenatide combined with OHAs

alone (mean 13.3 years vs 7.1 years);

Insulin (n=88) Non-insulin (n=100) P-value
(Table 3). This is an expected finding
Male, n (%) 43 (49%) 65 (65%) – as type 2 diabetic patients in practice
often require insulin in the later
Female, n (%) 45 (51%) 35 (35%) – stages of disease.
At six months, those patients
Age, years 58.7±10.2 56.3±9.9 p=0.11 who were taking exenatide with
(CI: 48.5 to 68.9) (CI: 46.4 to 66.2) OHAs achieved a significant mean
HbA1c reduction of 1.6±1.8%
Diabetes duration, years 13.3±6.8 7.1±5.2 p<0.0001 (p<0.0001), weight loss of 6.5±5.5kg
(CI: 6.5 to 20.1) (CI: 1.9 to 16.1) (5% weight loss; p<0.0001), and
BMI reduction of 2.2±1.9kg/m2
Baseline HbA1c, % 9.5±1.3 9.8±1.6 p=0.21 (p<0.0001). Patients taking exe-
(CI: 8.2 to 10.8) (CI: 8.2 to 11.4) natide with insulin achieved similar
results with a mean HbA1c reduction
Baseline weight, kg 118.2±18.5 121.5±23.9 p=0.30 of 1.6±1.4% (p<0.0001), weight loss
(CI: 99.7 to 136.7) (CI: 97.6 to 145.4) of 7.3±5.2kg (6% weight loss;
p<0.0001) and a BMI reduction of
Baseline BMI, kg/m2 41.8±6.4 41.4±8.0 p=0.69 2.6±1.9kg/m2 (p<0.0001); (Table 4).
(CI: 35.4 to 48.2) (CI: 33.4 to 49.4) After starting exenatide, in the
majority of cases diabetic medication
Table 3. Baseline characteristics of successful exenatide patients (values are presented as doses required changing. In those
means ± SD) patients on insulin, the mean daily
dose at baseline was 126.9±74.7 units.
The mean change in dose after six
Patients taking exenatide with insulin (n=88)
months of treatment with exenatide
HbA1c (%) Weight (kg) BMI
was a reduction in daily insulin dose
of 48±45.5 units/person (p<0.0001).
Baseline 9.5±1.3 118.2±18.5 41.8±6.4
This enabled 80% of patients to
(CI: 8.2 to 10.8) (CI: 99.7 to 136.7) (CI: 35.4 to 48.2)
reduce their dose of insulin, while
9% were able to come off insulin
Change at 6 months -1.6±1.4 -7.3±5.2 (6% loss) -2.6±1.9
altogether. Eight percent of patients
(CI: -3.0 to -0.2) (CI: -12.5 to -2.1) (CI: -4.5 to -0.7)
had a rise in their insulin dose, while
3% had no changes.
P-value (vs baseline) p<0.0001 p<0.0001 p<0.0001
Stopping or reducing diabetic
medication had a substantial impact
Patients taking exenatide with oral hypoglycaemic agents (n=100)
on the net cost of treatment with exe-
natide. At the start of treatment, the
HbA1c (%) Weight (kg) BMI additional cost of exenatide was
£68.24 (per person/month). In the
Baseline 9.8±1.6 121.5±23.9 41.4±8.0 group treated with exenatide and
(CI: 8.2 to 11.4) (CI: 97.6 to 145.4) (CI: 33.4 to 49.4) OHAs, the mean cost of diabetic med-
ication (per person/month) fell to
Change at 6 months -1.6±1.8 -6.5±5.5 (5% loss) -2.2±1.9 £54.90±16.8 above baseline, making a
(CI: -3.4 to 0.2) (CI: -12.0 to -1.0) (CI: -4.1 to -0.3) cost reduction of £13.34. In the group
of patients treated with exenatide and
P-value (vs baseline) p<0.0001 p<0.0001 p<0.0001 insulin, the mean cost of diabetic
medication (per person/month)
Table 4. Results at 6 months for patients on exenatide with and without insulin (values are presented reduced to £36.20±21.8 above base-
as means ± SD) line, making a greater cost reduction
of £32.04. As many patients were able
There was no significant differ- added to their regimen (88 patients), to cut their insulin dose, this offset the
ence at baseline in age, duration of and those who were exclusively tak- cost of exenatide.
diabetes, HbA1c, weight or BMI ing OHAs when exenatide was added
between the two groups (Table 2). (100 patients). There was no signifi- Discussion
Further analyses were carried out cant difference at baseline in mean In our retrospective case-series obser-
on the group of 188 patients who met age, HbA1c, weight or BMI between vation study we found that, at their
NICE target criteria after six months the two groups. There was, however, a statutory six-month review, 188 out of
and continued treatment with exe- significant difference between the 207 patients had made good clinical
natide. This group was sub-divided duration of diabetes. The patients on progress, enabling them to continue
into those who were being treated insulin had been diagnosed with dia- with exenatide. The mean HbA1c
with insulin when exenatide was betes for longer than those on OHAs reduction of 1.6%, achieved by the

392 PRACTICAL DIABETES VOL. 28 NO. 9 COPYRIGHT © 2011 JOHN WILEY & SONS

Cost and effectiveness of exenatide combined with insulin vs exenatide combined with OHAs
Key points
 Exenatide combined with insulin is as
clinically effective as exenatide combined
with oral hypoglycaemic agents (OHAs)
 Most patients treated with insulin were
able to reduce their insulin dose, with
80% reducing their dose of insulin (by a
mean of 48 units/day) and 9% stopping
insulin completely
 The monthly cost of exenatide in
combination with insulin is £18.70
less per patient than when exenatide
is combined with OHAs
group of patients who had originally
been treated with OHAs and also by
the group originally treated with
insulin, was well above the NICE tar-
get of a 1% drop by six months. In
addition, both groups achieved a
mean weight loss at six months
greater than the NICE target of 3%,
with patients who had been on insulin
achieving a non-significant greater
weight loss (6% vs 5%). We noted that
patients on insulin and exenatide
had been diabetic for a significantly
longer period of time than those on
OHAs and exenatide. Despite this,
the effectiveness of exenatide was
equivalent in both groups.
During treatment with exe-
natide, many patients had substan-
tial reductions (or managed to stop)
their co-existent diabetic medica-
tion, which resulted in a cost reduc-
tion. At six months, the additional
monthly cost of prescribing exe-
natide to the two groups of patients
was lower in the group who had orig-
inally been treated with insulin, as
substantial cost reductions were
achieved by being able either to stop
or reduce their insulin dose.
Although this is an off-label use
in the UK and the USA, the manu-
facturer has applied to the FDA
for a licence for use with insulin as
recent studies have proved safety
and efficacy.8,9
There have been few studies look-
ing at the effectiveness, particularly
cost-effectiveness, of commencing
exenatide treatment in patients
already managed with insulin. The
largest study of exenatide treatment
is the UK Association of British
Clinical Diabetologists national audit
of exenatide treatment, which
included data on 6717 patients, of
PRACTICAL DIABETES VOL. 28 NO. 9
whom 2257 were receiving treatment
with exenatide and insulin together
for 12 months. This study reported a
more modest reduction in HbA1c
(0.43%) but a reduction in weight
(5.8kg) comparable with our study.7
Two further UK studies have
demonstrated an impressive reduc-
tion in insulin dose when exenatide
therapy was added to the manage-
ment of insulin-treated type 2 dia-
betic subjects.10,11 Nayak et al. found
that the mean daily insulin dose
dropped from 144 units to 51 units at
six months.10 In a smaller study of
patients taking more than 100 units
of insulin daily, Price et al. found a
mean reduction of 40 units daily in
insulin requirements after three
months of treatment with exe-
natide.11 However, neither study was
able to demonstrate a significant
improvement in HbA1c from baseline
and only Nayak’s study demonstrated
weight loss (10.7kg at six months).
A multi-national study, which
added exenatide treatment to sub-
jects receiving basal insulin therapy
for type 2 diabetes, did demonstrate
a significantly greater reduction in
HbA1c when compared to the addi-
tion of placebo to basal insulin ther-
apy (fall in HbA1c 1.74% compared
to 1.04%; p<0.001). This study also
demonstrated significant weight loss
of 1.8kg after 30 weeks of exenatide
treatment compared to weight gain
of 1kg with addition of placebo, but
insulin requirements increased in
both groups to achieve the target
HbA1c of 7% (53mmol/mol).9
One American study of 188
patients did find reductions in HbA1c
(0.66%), weight (2.4kg), and insulin
dose (18 units/day) at six months.12
In contrast, our study demon-
strated a significantly greater improve-
ment in all three parameters. Daily
insulin dose requirements fell from
127 units at baseline to 79 units at six
months, a mean daily reduction of
48 units. In addition, subjects com-
pleting six months of treatment with
exenatide had a mean weight loss of
6.9kg and improved their HbA1c by a
mean of 1.6%. Furthermore, the
reduction in insulin dose achieved
during treatment with exenatide
enabled a monthly mean cost saving
of £18.70/patient originally treated
with insulin when compared to those
subjects originally receiving OHAs.
Original article
In conclusion, our study has
demonstrated that the addition of
exenatide therapy is beneficial to
both insulin-treated and tablet-
treated type 2 diabetes patients,
producing similar improvements in
HbA1c and reductions in weight after
six months’ therapy. However, greater
cost savings were achieved in subjects
originally treated with insulin.
Acknowledgements
We wish to thank the other members
of the West Suffolk Hospital Diabetes
Team who were involved in the man-
agement of these patients. (Consult-
ants: Eleanor Gurnell, Nishan
Wijenaike, Joohi Majeed. GP clinical
assistants: Matthew Lockyer, Robert
Bradley. Registrar: Leena Krishnan.
Diabetes specialist nurses: Liz Hartley,
Mandy Hunt, Susan Griggs, Rowena
Horsman. Senior dietitian: Isabel
Hooley. Senior pharmacist: Judith
Esterhuizen. Endocrine secretaries:
Joanne Rampley, Deirdre Brown.
Research secretary: Anne Moss).
Declaration of interests
Dr Clark has received honoraria
from Eli Lilly, Novo Nordisk, Merck
Sharp & Dohme, and Pfizer for edu-
cational meetings.
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