Journal of Medical Economics
ISSN: 1369-6998 (Print) 1941-837X (Online) Journal homepage: https://www.tandfonline.com/loi/ijme20
An analysis of the cost-effectiveness of starting
insulin detemir in insulin-naïve people with type 2
diabetes
Philip Home, Sei Hyun Baik, Guillermo González Gálvez, Rachid Malek &
Annie Nikolajsen
To cite this article: Philip Home, Sei Hyun Baik, Guillermo González Gálvez, Rachid Malek
& Annie Nikolajsen (2015) An analysis of the cost-effectiveness of starting insulin detemir in
insulin-naïve people with type 2 diabetes, Journal of Medical Economics, 18:3, 230-240, DOI:
10.3111/13696998.2014.985788
To link to this article: https://doi.org/10.3111/13696998.2014.985788
Published online: 21 Nov 2014.
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Journal of Medical Economics
1369-6998
doi:10.3111/13696998.2014.985788
Vol. 18, No. 3, 2015, 230–240
Article 0069.R2/985788
All rights reserved: reproduction in whole or part not permitted
Original article
An analysis of the cost-effectiveness of starting
insulin detemir in insulin-naı̈ve people with
type 2 diabetes
Philip Home
The Medical School, Newcastle University, Newcastle
upon Tyne, UK
Sei Hyun Baik
Division of Endocrinology, Korea University Guro
Hospital, Seoul, South Korea
Abstract
Aims:
There is limited evidence with respect to the cost-effectiveness of starting insulin in people with diabetes
outside the ‘western’ world. The aim of this study was to assess the cost-effectiveness of starting basal
insulin treatment with insulin detemir in people with type 2 diabetes (T2D) inadequately controlled on oral
glucose-lowering drugs (OGLDs) in Mexico, South Korea, India, Indonesia, and Algeria.
Guillermo González Gálvez
Instituto Jalisciense de Investigación en Diabetes y
Obesidad, Guadalajara, Mexico
Rachid Malek
Internal Medicine Department, University Hospital
Setif, Setif, Algeria
Annie Nikolajsen
Market Access – Value Communication, Novo Nordisk
A/S, Søborg, Denmark
Address for correspondence:
Professor Philip Home, ICM-Diabetes, The Medical
School, Framlington Place, Newcastle upon Tyne NE2
4HH, UK.
Tel: +44 191 208 7154; Fax: +44 191 208 0723;
philip.home@newcastle.ac.uk
Keywords:
Type 2 diabetes – Insulin detemir – Cost-effectiveness
– A1chieve
Methods:
The IMS CORE Diabetes Model was used to project clinical and cost outcomes over a 30-year time horizon.
Clinical outcomes, baseline characteristics and health state utility data were taken from the A1chieve study.
A 1-year analysis was also conducted based on treatment costs and quality-of-life data. Incremental costeffectiveness ratios (ICERs) were expressed as a fraction of GDP per capita, and WHO-CHOICE
recommendations (ICER53.0) used to define cost-effectiveness.
Results:
Starting insulin detemir was associated with a projected increase in life expectancy (1 year) and was
considered cost-effective in all of the studied populations with ICERs of 0.02 (Mexico), 0.00 (South Korea),
0.48 (India), 0.12 (Indonesia), and 0.88 (Algeria) GDP/quality-adjusted life-year. Cost-effectiveness was
maintained after conducting sensitivity analyses in the 30-year and 1-year analyses. A projected increase in
treatment costs was partially offset by a reduction in complications. The difference in overall costs between
insulin detemir and OGLDs alone was USD518, 1431, 3510, 15, and 5219, respectively.
Conclusion:
Changes in clinical outcomes associated with starting insulin detemir in insulin-naı̈ve individuals with T2D
resulted in health gains that made the intervention cost-effective in five countries with distinct healthcare
resources.
Accepted: 5 November 2014; published online: 21 November 2014
Citation: J Med Econ 2015; 18:230–40
Introduction
Recent estimates from the International Diabetes Federation (IDF) suggest that
382 million people worldwide have diabetes, of whom the majority (80%) live in
low- or middle-income countries1. By 2030, the global prevalence of diabetes is
estimated to increase by at least 50%; a corollary of increasing prevalence in
obesity, and greater life expectancy due to improving healthcare management
and lifestyle changes2. The rising burden of diabetes and scarcity of resources
worldwide highlight the need for not only efficacious, but also cost-effective,
solutions to improve the quality-of-life of people with diabetes, both in the
short-term and by reduction of long-term organ damage.
230
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
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Journal of Medical Economics
A goal in diabetes management is, then, to reduce the
risk of diabetes-related complications. Clinically, this
includes achieving as near-optimal glycemic control as
possible without increasing hypoglycemia and other treatment-related complications. However, achieving glycemic
targets remains a challenge in many people with type 2
diabetes (T2D)3–6. In most people with T2D, insulin therapy will be required in time to supplement the progressive
loss of -cell function, but starting insulin therapy is often
delayed due to barriers, including fear of hypoglycemic
events and weight gain, resistance to changes in regimens,
and higher treatment costs compared with non-insulin
therapy7. However, delaying insulin therapy, as well as
failing to ameliorate the risk of diabetes-related complications, may leave the individual with diabetes with poor
health-related quality-of-life (HRQoL)8. These factors
may result in increased resource utilization and a rise in
the overall costs associated with diabetes management9.
Clinical guidelines support the add-on of basal insulin
to existing regimens in people not achieving glycemic
goals while receiving oral glucose-lowering drugs
(OGLDs)10–12. In randomized clinical trials (RCTs) in
insulin-naı̈ve people with T2D, basal insulin analogs
have demonstrated better glycemic control with a lower
risk of hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin13–18. Furthermore, the
clinical effectiveness of basal insulin analogs in T2D has
been demonstrated in real-life observational studies5,19–23.
Observational data are often collected from large heterogeneous populations that help enhance the generalizability
of the clinical findings of RCTs. In addition, observational
studies often provide a more representative profile of
adverse events for people in routine care24.
A1chieve was a 24-week, observational study that
assessed the safety and clinical effectiveness of insulin
analogs OGLDs in 66,726 people with T2D. The study
was conducted in 28 countries outside the ‘western’ world
with varying healthcare resources and ethnic diversity.
The A1chieve study provides the opportunity to conduct
cost-effectiveness analyses in several non-western populations based on the type of insulin analog used and/or prior
insulin treatment, and in very different clinical environments. The aim of the current analysis was, therefore, to
assess the long- and short-term cost-effectiveness of starting basal insulin therapy with insulin detemir in people
with T2D inadequately controlled on OGLDs using clinical outcomes and specific HRQoL values from the
A1chieve study.
Materials and methods
The A1chieve study
The A1chieve study and its findings have been described
in detail elsewhere5,25. In summary, it was an observational
! 2014 Informa UK Ltd www.informahealthcare.com/jme
Volume 18, Number 3
March 2015
24-week study in insulin-naı̈ve (n ¼ 44,872) and insulinexperienced people (n ¼ 21,854) with T2D starting biphasic insulin aspart 30, insulin detemir or insulin aspart (all
Novo Nordisk, Bagsværd, Denmark) alone or in combination. The study showed that, in routine clinical practice
in all of the regions studied, people starting an analog
experienced clinically useful improvements in bloodglucose control with improved HRQoL without clinically
significant problems associated with hypoglycemia or
weight gain25. Similar findings were reported with insulin
detemir alone in both the insulin-naı̈ve and insulinexperienced groups.
Simulation cohort and assumptions
For the cost-effectiveness analyses, baseline characteristics
and the changes associated with starting insulin detemir
(including HbA1c, body mass index [BMI], lipid content,
systolic blood pressure, hypoglycemia, and EQ-5D-based
HRQoL) (Table 1) were derived from the A1chieve insulin-naı̈ve group (insulin detemir cohort). Our analysis was
country-based given that resource use, currency, and
healthcare structure differ between countries. A1chieve
study populations starting insulin detemir were large
enough (n4100) from Mexico (n ¼ 101), South Korea
(n ¼ 487), Indonesia (n ¼ 109), India (n ¼ 1491) and
Algeria (n ¼ 473) to be included in the analysis, and
only individuals with an HbA1c measurement at baseline
and after 24 weeks of insulin detemir therapy were
included in each cohort. In the analysis, we used studyspecific health state utility data (EQ-5D HRQoL) from
baseline and 24-week measurements25. A participant
number of 4100 per cohort was chosen to avoid the risk
that each analysis was unrepresentative of the underlying
population. The clinical and economic impact of starting
insulin detemir in each country was projected over a
30-year time horizon for the base-case scenario. We also
assumed that patients in the OGLD comparator arm stayed
on treatment with no added effect for 30 years in the base
case; this assumption was further challenged in the sensitivity analysis (see below). Both costs and health outcomes
were discounted at an annual rate of 3.0% throughout the
simulated periods.
A short-term analysis was also conducted for the first
year after starting insulin detemir. This analysis was based
only on the incremental cost of treatment (excluding costs
of complications and hospitalizations related to these
given that most diabetes-related complications occur in
the long-term) and the incremental effect on HRQoL.
Other clinical measures such as HbA1c, BMI, and hypoglycemia were not included in this analysis.
For each of the countries included, specific data were
collected independently of the investigators regarding
costs, as they are required for the analysis model. Costs
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
231
Journal of Medical Economics
Volume 18, Number 3
March 2015
were defined from a public healthcare perspective in all
countries. These costs included those associated with diabetes management (annual costs for other medications and
screening tests) and relevant co-morbid medical conditions (cardiovascular and renal complications, eye disease,
acute events, neuropathy, foot ulcer and amputation)26–29.
These data were taken from the existing literature, supplemented if necessary, and reviewed by clinical experts from
the countries concerned. The costs of insulin and OGLDs
were used as the treatment costs of the model and were
sourced from local Novo Nordisk affiliates. Background
mortality rates for each country were taken from World
Health Organization (WHO) data tables30.
CORE diabetes model
The IMS Centre for Outcomes REsearch (CORE)
Diabetes Model was used to determine the long-term
health and cost outcomes of starting treatment with insulin detemir in people with T2D inadequately controlled on
OGLDs. The CORE Diabetes Model is an interactive
computer simulation based on a network of Markov submodels that simulate complications often associated with
diabetes (cardiovascular disease, eye disease, hypoglycemia, ulcers, amputation, stroke, lactic acidosis, nephropathy, neuropathy, ketoacidosis, and mortality)31. These
sub-models incorporate time, state, time in state, and diabetes type-dependent probabilities derived from published
sources. Default probabilities are predominantly based on
results from the UKPDS, DCCT and Framingham studies31. The development and progression of multiple
inter-related complications are simulated using Monte
Carlo simulation with tracker variables. Cohort outcomes
are projected using several sources of information including baseline characteristics, history of complications, diabetes management and screening strategies, concomitant
medication, and changes in surrogate outcomes over time.
Baseline, clinical and economic data can be defined by
the user, thus providing a platform for calculating country-specific long-term outcomes for various clinical
settings using the best currently available data.
Statistics
Non-parametric bootstrapping was used in each simulation
(1000 people and 1000 bootstraps per country). The incremental cost-effectiveness ratio (ICER) is expressed as cost
per quality-adjusted life-year (QALY) (in both local currency and USD, exchange rates as of September 2013),
and also presented as a fraction of the gross domestic product (GDP) per capita for each country included in the
analysis. GDP data were taken from the World Bank for
201132. To determine the relative cost-effectiveness of an
intervention, the WHO CHOosing Interventions that are
232
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
Cost Effective (CHOICE) program recommends a threshold based on the GDP per capita33. This system considers
an intervention non-cost-effective at 43-times GDP per
capita, cost-effective at 1–3-times GDP per capita, highly
cost-effective at less than the GDP per capita or costsaving (dominant) if estimated overall costs of new treatment are less than comparator and QALY gained zero.
Several sensitivity analyses were conducted; these
included: extending the time horizon from 30 years to 50
years; applying no HbA1c deterioration with time compared with the base-case scenario where HbA1c was set
to deteriorate by 0.15%-units (1.6 mmol/mol) each year
after the first year; using the median HbA1c treatment
effect instead of the mean effect; using the first quartile
distribution of the HbA1c treatment effect (i.e., HbA1c
change in lowest 25% of the study population) instead
of the mean effect; incorporating the costs of one selfmeasured plasma glucose (SMPG) strip per day vs no
strips in the base case; adding another four medical consultations in the first year after starting insulin detemir,
based on public sector prices and where the first visit
reflects the cost of a specialist and subsequent visits that
of a general practitioner (GP) (the highest price of a
GP/specialist visit for each country was used in order to
be conservative); including two GP visits every year after
starting insulin detemir, also based on public sector prices,
but both visits reflecting the costs of a non-specialist GP
visit; using the average EQ-5D change from the A1chieve
study (þ0.174) rather than country-specific data; and
assuming insulin detemir is started anyway 5 years later
in the comparator arm. In the 1-year short-term analysis,
sensitivity analyses were conducted for the costs of strips
and for four medical consultations after starting insulin
detemir, compared with the absence of these factors in
the base-case analysis.
An analysis was also conducted to project for each country the maximum total costs (assuming the same clinical
outcome as measured in A1chieve) that were cost-effective
as defined by an ICER of 3.0-times GDP per capita.
Results
Cost-effectiveness, costs, and diabetes-related
complications
In the 30-year base case, the change in clinical outcomes
reported in A1chieve for insulin-naı̈ve individuals with
T2D starting insulin detemir (Table 1) was associated
with a projected increase in life expectancy in Mexico
(1.9 years), India (1.6 years), Algeria (0.8 years),
Indonesia (1.0 year) and South Korea (1.0 year)34.
Starting insulin detemir was consistently associated with
projected reductions in the modeled incidence of diabetesrelated complications compared with continuing OGLDs
www.informahealthcare.com/jme ! 2014 Informa UK Ltd
! 2014 Informa UK Ltd www.informahealthcare.com/jme
0.00/0
2.03/2.03
0.12/0.12
2.03/2.03
0.00/0
0.13/0.46
5.3 (1.3)/0.7 (0.9)**
3.3 (1.1)/0.6 (1.0)**
1.1 (0.3)/0.0 (0.3)
2.0 (1.2)/0.4 (1.1)y
4.8 (1.2)/0.4 (1.4)*
2.8 (1.0)/0.3 (1.1)**
1.2 (0.3)/0.0 (0.2)
2.0 (1.5)/0.3 (1.3)**
0.03/0.03
0.67/0.99
13 (11.9)
11 (10.1)
23 (21.1)
6 (5.5)
47 (43.1)
109
54.1/45.9
55.6 (9.1)
5.4 (4.0)
23.7 (3.4)/0.3 (1.6)
9.4 (1.7)/2.1 (1.6)*
79 (19)/23 (18)*
18.2/6.0
0.846 (0.2)/0.111 (0.2)*
128.4 (17.4)/2.1 (14.7)
Indonesia
112 (23.0)
130 (26.7)
119 (24.4)
6 (1.2)
169 (34.7)
487
52.6/47.4
58.4 (11.8)
10.2 (6.8)
24.5 (3.4)/0.2 (1.1)*
9.4 (1.8)/1.5 (1.8)*
79 (20)/16 (20)*
22.8/5.9
0.780 (0.2)/0.063 (0.2)*
127.2 (16.3)/2.3 (17.6)y
South Korea
Mean (SD or %), *p 0.001, **p 0.01, yp 0.05.
BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein; T2D, type 2 diabetes.
n
101
Sex, M/F, %
48.5/51.5
Age, years
55.6 (12.4)
Diabetes duration, years
9.4 (6.6)
28.7 (5.1)/0.2 (1.7)
BMI, kg/m2/change
HbA1c, %-units/change
10.1 (1.9)/2.2 (1.6)*
HbA1c, mmol/mol/change
87 (21)/24 (18)*
Dose/change (U/day)
24.6/6.0
EQ-5D/change
0.715 (0.2)/0.150 (0.3)*
Systolic blood pressure, mmHg/change
134.8 (19.6)/6.4 (17.4)*
Baseline complications, n (%)
Cardiovascular
14 (13.9)
Renal
30 (29.7)
Eye
24 (23.8)
Foot ulcer
2 (2.0)
Neuropathy
54 (53.5)
Lipids, mmol/L/change
Total cholesterol
5.7 (1.5)/0.6 (1.3)*
LDL cholesterol
2.9 (1.1)/0.0 (1.1)
HDL cholesterol
1.0 (0.3)/0.1 (0.3)
Triglycerides
2.3 (1.0)/0.4 (0.9)*
Hypoglycemia (events per 100 person-years)/change
Daytime
Major
0.00/0
Minor
0.64/0.51
Nocturnal
Major
0.00/0
Minor
0.26/0
Mexico
India
0.02/0.02
0.36/0.36
0.03/0.03
0.67/0.55
5.1 (1.3)/0.4 (1.1)*
3.1 (0.9)/0.4 (0.6)*
1.0 (0.3)/0.0 (0.3)
2.1 (1.0)/0.3 (0.6)*
271 (19.9)
275 (20.2)
162 (11.9)
59 (4.3)
246 (18.0)
1491
62.2/37.8
48.7 (9.5)
5.3 (3.2)
27.1 (3.5)/0.4 (0.9)*
9.3 (1.4)/2.1 (1.5)*
78 (15)/23 (16)*
18.4/0.4
0.473 (0.2)/0.322 (0.3)*
134.1 (19.0)/8.9 (17.2)*
Table 1. Baseline demographics and the change in clinical outcomes after 24 weeks from the A1chieve study in people with T2D starting insulin detemir.
0.00/0
0.41/0.11
0.00/0
0.85/0.17
4.5 (1.1)/0.16 (1.0)
2.8 (1.2)/0.1 (1.3)
1.1 (0.4)/0.0 (0.5)
1.6 (0.9)/0.1 (0.8)y
93 (19.7)
112 (23.7)
148 (31.3)
5 (1.1)
163 (34.5)
473
38.8/61.2
59.5 (9.9)
10.0 (6.1)
27.9 (4.8)/0.3 (1.3)*
9.3 (1.7)/1.5 (1.8)*
78 (19)/16 (20)*
22.5/11.3
0.772 (0.2)/0.064 (0.2)*
131.9 (18.6)/0.6 (34.1)
Algeria
Journal of Medical Economics
Volume 18, Number 3
March 2015
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
233
Journal of Medical Economics
Volume 18, Number 3
March 2015
Table 2. Cumulative incidence and estimated time alive and free of complications (years) over 30 years after starting insulin detemir compared with not
starting the insulin in people with T2D inadequately controlled on OGLDs.
Mexico
Any complication
Time to event (years)
Severe vision loss
Incidence (% people)
Time to event (years)
End-stage renal disease
Incidence (% people)
Time to event (years)
Myocardial infarction
Incidence (% people)
Time to event (years)
Ulcer
Incidence (% people)
Time to event (years)
South Korea
Indonesia
India
Algeria
Detemir
OGLD
Detemir
OGLD
Detemir
OGLD
Detemir
OGLD
Detemir
OGLD
0.6
0.3
1.0
0.7
2.0
1.3
3.2
1.9
1.6
1.1
16.4
12.2
23.1
9.9
7.2
11.0
9.7
9.9
5.5
13.9
8.8
12.6
7.8
16.0
12.1
14.8
8.3
13.3
11.0
12.3
8.6
13.6
20.0
11.4
5.1
11.4
10.3
10.4
2.9
14.1
7.7
13.0
3.6
16.6
11.2
14.8
5.0
13.9
9.6
13.0
40.9
11.8
47.5
9.7
31.4
10.5
35.5
9.5
25.5
12.8
32.6
11.6
30.5
14.7
38.4
12.9
22.8
12.9
27.2
12.0
27.4
12.0
28.0
10.2
28.6
9.9
30.2
8.9
16.1
12.7
18.3
11.7
18.4
15.1
22.3
13.4
17.4
12.9
19.2
12.0
OGLD, oral glucose-lowering drug; T2D, type 2 diabetes.
alone (Table 2). Overall, the reported reduction of cumulative incidence ranged between 25% (Algeria) and 38%
(Indonesia) for severe vision loss, 48% (Algeria) and
68% (India) for end-stage renal disease, 2% (Mexico)
and 17% (India) for foot ulcers, and 12% (South Korea)
and 22% (Indonesia) for myocardial infarction. The time
free of any complication was greater with insulin detemir
compared with OGLDs alone, with a difference between
treatment groups ranging from 0.3 years for South Korea to
1.3 years for India. For individual complications, similar
differences were universally observed, typically 1.0–2.0
extra years free of each complication in each country
(Table 2). The estimated QALY gains were 1.2 for
Algeria, 5.0 for India, 2.5 for Mexico, 1.8 for Indonesia,
and 1.0 for South Korea.
Projected treatment costs were 2–5-times greater in all
of the studied populations compared with OGLDs alone,
reflecting the additional costs of insulin therapy (Table 3).
However, costs associated with the management of diabetes complications were reduced in the insulin detemir
group, and thus the difference in overall costs was smaller
than the difference in treatment costs. Indeed, in Mexico,
Indonesia, and South Korea, discounted overall costs were
negligibly different between treatment groups (differences
in overall costs between insulin detemir and OGLDs:
USD518, 15, and 1431 per 30 years, respectively), while
in India (USD3510) and Algeria (USD5219) the cost
increments remained (Table 3).
The ICERs, expressed as incremental cost per QALY
gained, are presented in local currency, USD, and as a
fraction of GDP per capita in Table 4. The increment in
costs, QALYs, and life expectancy are also presented. For
Algeria and India, the ICERs, expressed as a fraction of
GDP per capita, were 0.88 and 0.48, while in Mexico,
Indonesia, and South Korea they were close to zero
234
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
(0.02, 0.12, and 0.00, respectively), meeting WHO
CHOICE guidelines for being highly cost-effective in all
countries.
In the short-term analysis, the 1-year ICER, expressed
as GDP fractional cost per QALY gained, was still highly
cost-effective in India (0.71), Mexico (0.48), Indonesia
(0.68), and South Korea (0.18). In Algeria it was 1.48,
meeting WHO Choice guidelines for cost-effectiveness
(53.0) (Table 4).
Sensitivity analysis
If the model was run for 30 years and insulin detemir was
started in the OGLD reference group 5 years after the
treatment group began it, there is little change in the
ICERs (small tendency to be lower) compared with
the base case (Table 5). Similarly, increasing the time
horizon to 50 years, using the average global EQ-5D
instead of country-specific values, having no HbA1c
deterioration with time compared with the base-case scenario, using the median HbA1c treatment effect instead of
the mean effect, having two GP visits every year after
starting insulin detemir, or including the costs of four additional GP visits in the first year, had very little effect on
the ICERs (Table 5). However, the results were more sensitive to using the first quartile distribution of the HbA1c
treatment effect rather than the mean HbA1c, or including
the costs of one SMPG strip per day, but, even with these
changes, the ICERs expressed as GDP per capita per
QALY were still within the cost-effective range (53.0).
A cost-effectiveness threshold analysis showed that the
maximum percentage increase of total costs that would
deliver an ICER of 3.0 GDP per capita was 94% for
Mexico, 180% for South Korea, 76% for Indonesia,
194% for India, and 79% for Algeria. In the 1-year
www.informahealthcare.com/jme ! 2014 Informa UK Ltd
OGLD
880,261
MXNDZD
10,563
175,516
MXNDZD
2106
390,242
MXNDZD
4683
314,503
MXNDZD
3774
1,315,170
MXNDZD
15,782
636,139
MXNDZD
7634
404,847
MXNDZD
4858
274,185
MXNDZD
3290
204,439
MXNINR
3680
56,519
MXNINR
1017
79,366
MXNINR
1428
340,325
MXNINR
6,126
OGLD
USD
USD
Complication costs
Local currency
USD
Management costs
Local currency
USD
Treatment costs
Local currency
Total costs
Local currency
Currency conversions as of September 2013 (1 MXN ¼ 0.07 USD, 1 KRW ¼ 0.0009 USD, 1 IDR ¼ 0.0001 USD, 1 INR ¼ 0.018 USD, 1 DZD ¼ 0.012 USD).
OGLD, oral glucose-lowering drug.
150,114
MXNINR
2702
154,066,000
MXNIDR
15,407
129,676,000
MXNIDR
12,968
39,862,000
MXNKRW
36,673
1,020,704
MXNMXN
71,450
899,309
MXN
62,952
37,039,000
MXNKRW
34,076
58,254
MXNINR
1048
42,726,000
MXNIDR
4273
43,722,000
MXNIDR
4372
1,348,000
MXNKRW
1240
36,228
MXNMXN
2536
40,408
MXN
2829
1,420,000
MXNKRW
1306
326,978
MXNINR
5886
29,208,000
MXNIDR
2920
59,913,000
MXNIDR
5991
2,196,000
MXNKRW
2020
28,668
MXNMXN
2007
138,478
MXN
9694
4,963,000
MXNKRW
4566
535,345
MXNINR
9,636
226,000,000
MXNIDR
22,600
233,311,000
MXNIDR
24,031
43,406,000
MXNKRW
39,933
43,422,000
MXNKRW
39,948
1,085,600
MXNMXN
75,992
1,078,195
MXN
75,474
Detemir
OGLD
Detemir
OGLD
Detemir
OGLD
Detemir
March 2015
Discussion
India
Indonesia
South Korea
Mexico
Table 3. Direct costs per patient of diabetes care simulated over 30 years with insulin detemir compared with OGLDs alone.
! 2014 Informa UK Ltd www.informahealthcare.com/jme
Volume 18, Number 3
analysis, the ICER, expressed as a fraction of GDP per
QALY, also remained cost-effective (53.0) after conducting sensitivity analyses for the cost of SMPG strips and
the cost of four GP visits after starting insulin detemir
(Table 5).
Algeria
Detemir
Journal of Medical Economics
In this analysis, costs and outcomes associated with starting insulin detemir in individuals with T2D on oral agents
alone were simulated over a 30-year time horizon using the
previously validated CORE Diabetes Model, and were
found to be cost-effective in healthcare settings as different
as those in Algeria, Mexico, India, Indonesia, and South
Korea. To ensure local validity, we used locally specific
baseline clinical characteristics, and within-study surrogate and HRQoL outcomes, together with local costs
both for current therapies and long-term management of
complications. With this approach, longer-term discounted costs were essentially neutral in Mexico,
Indonesia, and South Korea, while the incremental costs
in Algeria and India, when calculated as the ratio to the
modeled QALY gain (ICER, and expressed as a fraction of
GDP per capita), were cost-effective based on WHO
CHOICES criteria (Table 4). These outcomes are likely
to reflect the major improvements in metabolic outcomes
in routine care in the A1chieve population, together with
the useful improvements in measured HRQoL, and the
lack of deterioration in tolerability and safety issues such
as hypoglycemia and weight gain. Indeed, the difference in
QALY gains between countries (e.g., 5.0 for India, 1.0 for
South Korea) is likely to be largely driven by the reduction
in HbA1c reported in the A1chieve study; the average endof-study HbA1c for India was 7.2% (change from baseline:
2.1%), whereas the average end-of-study HbA1c for
South Korea was 7.9% (change from baseline: 1.5%).
When modeled on a 30-year time horizon, the metabolic changes are associated with a consistent reduction in
the incidence of major diabetes-related health outcomes
such as visual loss and myocardial infarction. Accordingly,
there is also a gain in life expectancy. Findings of improved
metabolic outcomes in the short-term have been consistent with insulin detemir in T2D in both RCTs and observational studies, although the extent of the improvement
is often not as large in the RCTs as in the studies done in
routine clinical practice such as A1chieve5,13–15,17,19,21,23.
A 30-year time horizon was judged realistic, as most people
in the modeled cohort would be expected to die within
that time, and such a time horizon will allow the capturing
of the relevant costs and outcomes. Indeed, extending the
time horizon to 50 years in the sensitivity analysis made
very little difference to the final cost-effectiveness results.
Although data from RCTs are regarded as the ‘gold
standard’ with regard to informing policy-makers and
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
235
Journal of Medical Economics
Volume 18, Number 3
March 2015
Table 4. Long-term and short-term cost-effectiveness of starting insulin detemir in people with T2D inadequately controlled on OGLDs. Costs expressed per
patient.
Mexico
30-year ICER (cost per QALY gained) (base case)
Local currency
2887 MXN (dominant)
USD
222
GDP fraction
0.02
Incremental cost
7404
Incremental QALY
2.57
Incremental LE (years)
1.19
1-year ICER (cost per QALY gained)
Local currency
62,952 MXN
USD
4835
GDP fraction
0.48
Incremental cost
9443 MXN
Incremental QALY
0.15
Incremental LE (years)
–
South Korea
Indonesia
India
Algeria
15,139 KRW
14
0.00
16,231 KRW
1.07
0.60
3,995,329 IDR
415
0.12
7,310,250 IDR
1.83
0.61
39,214 INR
707
0.48
195,020 INR
4.97
0.90
368,200 DZD
4625
0.88
434,909 DZD
1.18
0.50
4,273,409 KRW
3935
0.18
269,225 KRW
0.06
–
22,920,222 IDR
2381
0.68
2,544 145 IDR
0.11
–
58,454 INR
1054
0.71
18,822 INR
0.322
–
617,658 DZD
7758
1.48
39,530 DZD
0.064
–
Currency conversions as of September 2013 (1 MXN ¼ 0.07 USD, 1 KRW ¼ 0.0009 USD, 1 IDR ¼ 0.0001 USD, 1 INR ¼ 0.018 USD, 1 DZD ¼ 0.012 USD).
GDP, gross domestic product; ICER, incremental cost-effectiveness ratio; LE, life expectancy; OGLD, oral glucose-lowering drug; QALY, quality-adjusted life-year;
T2D, type 2 diabetes.
technology appraisals11, the presented analysis is based on
observational data. The use of A1chieve observational
data has the advantage of reflecting what happens in routine clinical practice. In reality, the short-term metabolic
gains found in A1chieve are replicated in observational
studies in longer developed (‘western’) economies35.
Thus, while our findings are not based on results from
RCTs, they are, in fact, based on clinical practice in the
real world.
Cost-effectiveness analyses are inherently comparative,
both for costs and outcomes, and a limitation of our study is
the assumption in the base case that the comparator group
continues current OGLD therapy indefinitely. We address
this limitation by estimating cost-effectiveness on a 1-year
time horizon, and by sensitivity analyses allowing that
insulin detemir is started anyway after 5 years in the
OGLD group. In the 1-year scenario, based only on the
incremental cost of treatment and the incremental effect
on HRQoL, cost-effectiveness is not as good as in the base
case, yet starting insulin detemir is still cost-effective using
WHO CHOICES criteria and, indeed, in three countries
still highly cost-effective. In the later-start sensitivity analysis, insulin detemir is still cost-effective over a 30-year
time horizon, even if it is started in the OGLD group
5 years later than in the base case.
Advantages of our approach include the relatively
broad population base, and the use of country-specific
data to ensure local relevance of the findings. While the
findings are specific to the countries concerned, it is clear
that their consistency implies that starting insulin detemir
is likely to be cost-effective or even highly cost-effective in
most other countries. However, because we find broad differences in the gain of life-years free of complications
between countries, and because the incremental healthcare costs varied widely between countries, it is not
236
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
possible to make any approach to specific estimates for
any other country. Nevertheless, other studies in different
resource environments have been used to evaluate the
cost-effectiveness of insulin detemir, in particular using
US and German populations36,37. These studies also used
the CORE Diabetes Model and projected, using a 35-year
time horizon, improved quality-adjusted life expectancy
with insulin detemir compared with OGLDs alone; in
the US study, a discounted life expectancy gain of 0.464
years and an ICER of USD7412 per QALY gained were
reported in the base case36, while in the German study, life
expectancy gain was 0.28 years with cost-saving in the
insulin detemir arm37. In agreement with our findings,
cost savings in both studies were driven by the projected
decrease in diabetes-related complications associated with
insulin detemir therapy.
Our study has other limitations. A1chieve was not a
randomized study, thus no other comparator than continued baseline treatment was available for modeling. Other
insulins were studied in A1chieve, and similar short-term
clinical outcomes were reported, but the populations allocated to each insulin would have been likely to differ in
unknown ways. It could be argued that we should model
against another insulin as a comparator, but no data are
available from A1chieve as to what outcomes would have
been found with such an insulin in a population similar to
that started on insulin detemir. Clearly, being an observational study, we can only assess the cost-effectiveness associated with starting insulin detemir; as we note in our
original paper5, the lack of increase in hypoglycemia or
body weight, and the improvement in systolic blood pressure, suggests that starting the insulin analog was an opportunity for enhanced lifestyle modification.
As a limitation, there was a lack of published resources
specific to the studied populations in terms of costs.
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Journal of Medical Economics
Volume 18, Number 3
March 2015
Table 5. Sensitivity analysis of starting insulin detemir in people with T2D inadequately controlled on OGLDs.
Cost
Mexico
30-year analysis
Base case
50-year time horizon
No HbA1c deterioration
Median treatment effect (HbA1c)
Quartile 1 treatment effect (HbA1c)
Including costs of SMPG strips
4 additional visits in the first year after
starting insulin detemir
2 GP visits every year after starting
insulin detemir
Average global EQ-5D
Insulin started after 5 years
1-year analysis
Base case
Including costs of SMPG strips
4 additional visits after starting
insulin detemir
South Korea
30-year analysis
Base case
50-year time horizon
No HbA1c deterioration
Median treatment effect (HbA1c)
Quartile 1 treatment effect (HbA1c)
Including costs of SMPG strips
4 additional visits in the first year
after starting insulin detemir
2 GP visits every year after starting
insulin detemir
Average global EQ-5D
Insulin started after 5 years
1-year analysis
Base case
Including costs of SMPG strips
4 additional visits after starting
insulin detemir
Indonesia
30-year analysis
Base case
50-year time horizon
No HbA1c deterioration
Median treatment effect (HbA1c)
Quartile 1 treatment effect (HbA1c)
Including costs of SMPG strips
4 additional visits in the first year
after starting insulin detemir
2 GP visits every year after starting
insulin detemir
Average global EQ-5D
Insulin started after 5 years
1-year analysis
Base case
Including costs of SMPG strips
4 additional visits after starting
insulin detemir
India
30-year analysis
Base case
50-year time horizon
No HbA1c deterioration
Median treatment effect (HbA1c)
Quartile 1 treatment effect (HbA1c)
Including costs of SMPG strips
4 additional visits in the first year
after starting insulin detemir
2 GP visits every year after starting
insulin detemir
QALY
(MXN)
Incremental
cost
Incremental
QALY
Increased LE
(years)
(MXN)
ICER
(MXN)
1,078,195
1,085,111
1,019,232
1,081,730
1,141,864
1,106,004
1,081,108
8.56
8.57
8.85
8.50
8.00
8.56
8.56
7404
2542
35,599
3869
56,265
20,405
4492
2.57
2.57
2.57
2.51
2.01
2.57
2.57
1.19
1.21
1.10
1.13
0.56
1.19
1.19
Dominant
Dominant
Dominant
Dominant
28,039
7,955
Dominant
1,091,736
8.56
6136
2.57
1.19
2392
1,078,195
1,078,195
8.83
8.56
7404
21,695
2.84
1.30
1.19
0.72
12,273
14,737
15,273
0.87
0.87
0.87
9443
11,907
12,443
0.15
0.15
0.15
–
–
–
(KRW)
(KRW)
Dominant
Dominant
62,952
79,382
82,952
(KRW)
43,422,013
43,517,627
41,469,854
43,787,426
45,254,759
44,815,361
43,459,422
6.55
6.55
6.75
6.46
6.20
6.55
6.55
16,231
70,038
8346
381,644
1,848,977
1,409,578
53,619
1.07
1.07
1.08
0.97
0.71
1.07
1.07
0.60
0.60
0.58
0.48
0.17
0.60
0.60
15,139
65,323
7726
392,045
2,591,132
1,314,779
50,013
43,606,209
6.55
200,406
1.07
0.60
186,928
43,422,034
43,422,034
7.64
6.55
16,231
281,319
2.16
0.59
0.60
0.39
7528
479,504
508,241
650,922
546,751
0.84
0.84
0.84
269,225
411,907
307,735
0.06
0.06
0.06
–
–
–
(IDR)
(IDR)
4,273,409
6,538,200
4,884,679
(IDR)
233,310,512
235,955,583
227,093,595
235,598,240
243,371,064
271,009,642
233,844,469
8.59
8.62
8.80
8.55
8.28
8.59
8.59
7,310,250
8,788,811
8,598,181
9,597,977
17,370,801
45,009,379
7,844,231
1.83
1.86
1.83
1.79
1.52
1.83
1.83
0.61
0.65
0.56
0.58
0.32
0.61
0.61
3,995,329
4,719,843
4,693,507
5,376,238
11,412,226
24,599,335
4,287,170
235,600,622
8.59
9,600,384
1.83
0.61
5,246,975
233,310,489
233,310,489
9.31
8.59
7,310,250
2,355,504
2.55
0.85
0.61
0.35
2,865,537
Dominant
5,232,238
8,524,538
5,782,238
0.96
0.96
0.96
2,544,145
5,836,445
3,094,145
0.11
0.11
0.11
–
–
–
22,920,222
52,580,582
27,875,177
(INR)
(INR)
(INR)
535,345
545,770
515,254
542,774
552,122
618,761
536,122
12.72
12.81
13.05
12.49
12.19
12.72
12.72
195,020
200,378
200,589
202,449
211,797
278,436
195,796
4.97
5.03
4.98
4.75
4.44
4.97
4.97
0.90
0.94
0.73
0.72
0.48
0.90
0.90
39,214
39,819
40,323
42,648
47,660
55,987
39,370
537,916
12.72
197,591
4.97
0.90
39,731
(continued )
! 2014 Informa UK Ltd www.informahealthcare.com/jme
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
237
Journal of Medical Economics
Volume 18, Number 3
March 2015
Table 5. Continued.
Average global EQ-5D
Insulin started after 5 years
1-year analysis
Base case
Including costs of SMPG strips
4 additional visits after starting
insulin detemir
Algeria
30-year analysis
Base case
50-year time horizon
No HbA1c deterioration
Median treatment effect (HbA1c)
Quartile 1 treatment effect (HbA1c)
Including costs of SMPG strips
4 additional visits in the first year
after starting insulin detemir
2 GP visits every year after starting
insulin detemir
Average global EQ-5D
Insulin started after 5 years
1-year analysis
Base case
Including costs of SMPG strips
4 additional visits after starting
insulin detemir
Cost
QALY
Incremental
cost
535,345
535,345
10.81
12.72
25,435
31,924
26,235
0.79
0.79
0.79
(DZD)
Incremental
QALY
Increased LE
(years)
195,020
71,697
3.07
2.02
0.90
0.48
63,511
35,536
18,822
25,311
19,622
0.32
0.32
0.32
–
–
–
58,454
78,606
60,938
(DZD)
ICER
(DZD)
1,315,170
1,315,951
1,311,148
1,312,359
1,315,011
1,498,414
1,316,626
8.02
8.02
8.23
7.99
7.65
8.02
8.02
434,909
435,554
441,662
432,097
434,750
618,152
436,365
1.18
1.18
1.18
1.14
0.81
1.18
1.18
0.50
0.50
0.46
0.46
0.11
0.50
0.50
368,200
369,445
375,048
378,181
539,454
523,336
369,433
1,317,461
8.02
437,200
1.18
0.50
370,140
1,315,170
1,315,170
9.28
8.02
434,909
176,584
2.44
0.57
0.50
0.30
178,144
309,853
55,529
71,524
57,029
0.83
0.83
0.83
39,530
55,526
41,030
0.06
0.06
0.06
–
–
–
617,658
867,588
641,096
GDP, gross domestic product; GP, general practitioner; ICER, incremental cost-effectiveness ratio; LE, life expectancy; OGLD, oral glucose-lowering drug; QALY,
quality-adjusted life-year; SMPG, self-measured plasma glucose; T2D, type 2 diabetes.
This was addressed by obtaining estimates from two or
three local experts in each country where data were lacking, and by asking them to comment on the obtained estimates, but the likely validity of this approach is not
known26–29. However, the approach was undertaken in
five different countries and, thus, five sets of local experts,
and, as the findings of high cost-effectiveness applied to
all five countries, and were robust on sensitivity analyses,
it would seem that variance in cost estimates were not
a problem for the study.
Costs associated with complications comprise a large
proportion of diabetes-related healthcare budgets when
estimated from countries as diverse as Tanzania and the
US, Mexico, and South Korea38–41. In the present analysis,
while projected treatment costs associated with starting
insulin detemir were greater in the studied populations
compared with OGLDs, and continued to be throughout
the 30-year time horizon, they were partially (Algeria and
India) or in essence completely (Indonesia, South Korea,
Mexico) offset by the observed reduction in the costs associated with the management of diabetes-related complications. A problem for funders and policymakers is that, in
diabetes care, costs have to be incurred upfront to gain
savings decades later. An Indian study, for example,
found that 60% of people had to use personal savings for
their diabetes care, while only 2% of people on high
incomes had insurance coverage for diabetes42. In these
circumstances, our finding that starting insulin detemir
238
Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.
was cost-effective according to GDP criteria even over
1 year is potentially helpful: an early investment delivering
an early healthcare gain.
A concern here is that we might not have captured all
the costs associated with starting the insulin analog. In
many of these countries, educational support teams are
not available for insulin starters, but, if provided, would
then add to costs, possibly for the duration of insulin therapy. However, equally, diabetes nurses/educators may
reduce time needed with more expensive medical staff.
Here, using sensitivity analyses, we modeled increased
doctor support in the first year as being more relevant to
the countries studied, but such extra costs made little difference to cost-effectiveness. Similarly, insulin therapy
may require further SMPG11, but this did not substantially
affect overall costs either. To further address the hypothetical need for additional resources associated with starting
insulin detemir, a sensitivity analysis was conducted that
determined the maximum potential increase in total costs
that would deliver an ICER of 3.0 GDP per capita.
Although these values ranged from 76–194% for the five
countries, it is clear that the use of additional resources
is plausible without compromising cost-effectiveness. In
conclusion, the changes in surrogate outcomes associated
with starting insulin detemir in insulin-naı̈ve people with
T2D resulted in health gains that made the intervention
highly cost-effective in five countries with distinct healthcare resources. A range of sensitivity analyses supported
www.informahealthcare.com/jme ! 2014 Informa UK Ltd
Journal of Medical Economics
this conclusion and, indeed, using a 1-year time horizon,
the intervention was still cost-effective compared to the
baseline state.
Transparency
Declaration of funding
This research was supported by Novo Nordisk.
Declaration of financial/other relationships
PH, SB, GGG, and RM, for themselves or institutions with
which they are connected, have received funding from Novo
Nordisk for advisory, speaker, and research activities, including
in regard of the A1chieve study. AN is an employee of Novo
Nordisk. JME peer reviewers on this manuscript have no relevant
financial or other relationships to disclose.
Acknowledgments
We thank all the people with diabetes and the local investigators
who took part in the study. The authors take full responsibility for
the data and analysis supporting this study, and the results and
discussion presented, but are grateful to Steven Barberini of
Watermeadow for writing assistance, and Last Mile P/S for assistance with analyses, funded by Novo Nordisk.
Previous presentation: Life expectancy values reported here in
each of the studied populations have been previously published in
abstract form at the ISPOR 18th Annual International Meeting,
New Orleans, LA, May 201334.
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