Journal of Medical Economics Vol. 18, No.

3, 2015, 230–240

1369-6998 Article 0069.R2/985788

doi:10.3111/13696998.2014.985788 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
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15

Philip Home Abstract

The Medical School, Newcastle University, Newcastle
upon Tyne, UK Aims:
There is limited evidence with respect to the cost-effectiveness of starting insulin in people with diabetes
Sei Hyun Baik outside the ‘western’ world. The aim of this study was to assess the cost-effectiveness of starting basal
Division of Endocrinology, Korea University Guro insulin treatment with insulin detemir in people with type 2 diabetes (T2D) inadequately controlled on oral
Hospital, Seoul, South Korea
glucose-lowering drugs (OGLDs) in Mexico, South Korea, India, Indonesia, and Algeria.
Guillermo González Gálvez
For personal use only.

Instituto Jalisciense de Investigación en Diabetes y Methods:

Obesidad, Guadalajara, Mexico The IMS CORE Diabetes Model was used to project clinical and cost outcomes over a 30-year time horizon.
Rachid Malek Clinical outcomes, baseline characteristics and health state utility data were taken from the A1chieve study.
Internal Medicine Department, University Hospital A 1-year analysis was also conducted based on treatment costs and quality-of-life data. Incremental cost-
Setif, Setif, Algeria effectiveness ratios (ICERs) were expressed as a fraction of GDP per capita, and WHO-CHOICE
recommendations (ICER53.0) used to define cost-effectiveness.
Annie Nikolajsen
Market Access – Value Communication, Novo Nordisk
A/S, Søborg, Denmark 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),
Address for correspondence: 0.48 (India), 0.12 (Indonesia), and 0.88 (Algeria) GDP/quality-adjusted life-year. Cost-effectiveness was
Professor Philip Home, ICM-Diabetes, The Medical
maintained after conducting sensitivity analyses in the 30-year and 1-year analyses. A projected increase in
School, Framlington Place, Newcastle upon Tyne NE2
treatment costs was partially offset by a reduction in complications. The difference in overall costs between
4HH, UK.
Tel: +44 191 208 7154; Fax: +44 191 208 0723; insulin detemir and OGLDs alone was USD518, 1431, 3510, 15, and 5219, respectively.
philip.home@newcastle.ac.uk
Conclusion:
Changes in clinical outcomes associated with starting insulin detemir in insulin-naı̈ve individuals with T2D
Keywords:
Type 2 diabetes – Insulin detemir – Cost-effectiveness resulted in health gains that made the intervention cost-effective in five countries with distinct healthcare
– A1chieve 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. www.informahealthcare.com/jme ! 2014 Informa UK Ltd

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 treat-
ment-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 ther-
apy will be required in time to supplement the progressive
Journal of Medical Economics Volume 18, Number 3 March 2015
24-week study in insulin-naı̈ve (n ¼ 44,872) and insulin-
experienced people (n ¼ 21,854) with T2D starting bipha-
sic insulin aspart 30, insulin detemir or insulin aspart (all
Novo Nordisk, Bagsværd, Denmark) alone or in combin-
ation. The study showed that, in routine clinical practice
in all of the regions studied, people starting an analog
experienced clinically useful improvements in blood-
glucose control with improved HRQoL without clinically
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
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15
therapy7. However, delaying insulin therapy, as well as
failing to ameliorate the risk of diabetes-related complica-
tions, 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
For personal use only.
risk of hypoglycemia compared with human neutral pro-
tamine 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 hetero-
geneous 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 popula-
tions based on the type of insulin analog used and/or prior
insulin treatment, and in very different clinical environ-
ments. The aim of the current analysis was, therefore, to
assess the long- and short-term cost-effectiveness of start-
ing basal insulin therapy with insulin detemir in people
with T2D inadequately controlled on OGLDs using clin-
ical 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
significant problems associated with hypoglycemia or
weight gain25. Similar findings were reported with insulin
detemir alone in both the insulin-naı̈ve and insulin-
experienced 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 insu-
lin-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 study-
specific 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 sensi-
tivity 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 hypo-
glycemia 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 dia-
betes management (annual costs for other medications and
screening tests) and relevant co-morbid medical condi-
tions (cardiovascular and renal complications, eye disease,
acute events, neuropathy, foot ulcer and amputation)26–29.
These data were taken from the existing literature, supple-
mented 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
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15
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 insu-
lin detemir in people with T2D inadequately controlled on
OGLDs. The CORE Diabetes Model is an interactive
computer simulation based on a network of Markov sub-
models that simulate complications often associated with
For personal use only.
diabetes (cardiovascular disease, eye disease, hypogly-
cemia, ulcers, amputation, stroke, lactic acidosis, nephro-
pathy, neuropathy, ketoacidosis, and mortality)31. These
sub-models incorporate time, state, time in state, and dia-
betes type-dependent probabilities derived from published
sources. Default probabilities are predominantly based on
results from the UKPDS, DCCT and Framingham stu-
dies31. 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 includ-
ing baseline characteristics, history of complications, dia-
betes 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 coun-
try-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 incre-
mental cost-effectiveness ratio (ICER) is expressed as cost
per quality-adjusted life-year (QALY) (in both local cur-
rency and USD, exchange rates as of September 2013),
and also presented as a fraction of the gross domestic prod-
uct (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 thresh-
old 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 cost-
saving (dominant) if estimated overall costs of new treat-
ment 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 com-
pared 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 self-
measured plasma glucose (SMPG) strip per day vs no
strips in the base case; adding another four medical con-
sultations 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 cou-
ntry 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 diabetes-
related complications compared with continuing OGLDs
www.informahealthcare.com/jme ! 2014 Informa UK Ltd
 Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15
For personal use only.

Table 1. Baseline demographics and the change in clinical outcomes after 24 weeks from the A1chieve study in people with T2D starting insulin detemir.

Mexico South Korea Indonesia India Algeria

n 101 487 109 1491 473

Sex, M/F, % 48.5/51.5 52.6/47.4 54.1/45.9 62.2/37.8 38.8/61.2
Age, years 55.6 (12.4) 58.4 (11.8) 55.6 (9.1) 48.7 (9.5) 59.5 (9.9)

! 2014 Informa UK Ltd www.informahealthcare.com/jme

Diabetes duration, years 9.4 (6.6) 10.2 (6.8) 5.4 (4.0) 5.3 (3.2) 10.0 (6.1)
BMI, kg/m2/change 28.7 (5.1)/0.2 (1.7) 24.5 (3.4)/0.2 (1.1)* 23.7 (3.4)/0.3 (1.6) 27.1 (3.5)/0.4 (0.9)* 27.9 (4.8)/0.3 (1.3)*
HbA1c, %-units/change 10.1 (1.9)/2.2 (1.6)* 9.4 (1.8)/1.5 (1.8)* 9.4 (1.7)/2.1 (1.6)* 9.3 (1.4)/2.1 (1.5)* 9.3 (1.7)/1.5 (1.8)*
HbA1c, mmol/mol/change 87 (21)/24 (18)* 79 (20)/16 (20)* 79 (19)/23 (18)* 78 (15)/23 (16)* 78 (19)/16 (20)*
Dose/change (U/day) 24.6/6.0 22.8/5.9 18.2/6.0 18.4/0.4 22.5/11.3
EQ-5D/change 0.715 (0.2)/0.150 (0.3)* 0.780 (0.2)/0.063 (0.2)* 0.846 (0.2)/0.111 (0.2)* 0.473 (0.2)/0.322 (0.3)* 0.772 (0.2)/0.064 (0.2)*
Systolic blood pressure, mmHg/change 134.8 (19.6)/6.4 (17.4)* 127.2 (16.3)/2.3 (17.6)y 128.4 (17.4)/2.1 (14.7) 134.1 (19.0)/8.9 (17.2)* 131.9 (18.6)/0.6 (34.1)
Baseline complications, n (%)
Cardiovascular 14 (13.9) 112 (23.0) 13 (11.9) 271 (19.9) 93 (19.7)
Renal 30 (29.7) 130 (26.7) 11 (10.1) 275 (20.2) 112 (23.7)
Eye 24 (23.8) 119 (24.4) 23 (21.1) 162 (11.9) 148 (31.3)
Foot ulcer 2 (2.0) 6 (1.2) 6 (5.5) 59 (4.3) 5 (1.1)
Neuropathy 54 (53.5) 169 (34.7) 47 (43.1) 246 (18.0) 163 (34.5)
Lipids, mmol/L/change
Total cholesterol 5.7 (1.5)/0.6 (1.3)* 4.8 (1.2)/0.4 (1.4)* 5.3 (1.3)/0.7 (0.9)** 5.1 (1.3)/0.4 (1.1)* 4.5 (1.1)/0.16 (1.0)
LDL cholesterol 2.9 (1.1)/0.0 (1.1) 2.8 (1.0)/0.3 (1.1)** 3.3 (1.1)/0.6 (1.0)** 3.1 (0.9)/0.4 (0.6)* 2.8 (1.2)/0.1 (1.3)
HDL cholesterol 1.0 (0.3)/0.1 (0.3) 1.2 (0.3)/0.0 (0.2) 1.1 (0.3)/0.0 (0.3) 1.0 (0.3)/0.0 (0.3) 1.1 (0.4)/0.0 (0.5)
Triglycerides 2.3 (1.0)/0.4 (0.9)* 2.0 (1.5)/0.3 (1.3)** 2.0 (1.2)/0.4 (1.1)y 2.1 (1.0)/0.3 (0.6)* 1.6 (0.9)/0.1 (0.8)y
Hypoglycemia (events per 100 person-years)/change
Daytime
Major 0.00/0 0.03/0.03 0.00/0 0.03/0.03 0.00/0
Minor 0.64/0.51 0.67/0.99 2.03/2.03 0.67/0.55 0.85/0.17
Nocturnal
Major 0.00/0 0.00/0 0.12/0.12 0.02/0.02 0.00/0
Minor 0.26/0 0.13/0.46 2.03/2.03 0.36/0.36 0.41/0.11
Journal of Medical Economics

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.
Volume 18, Number 3

Cost-effectiveness of insulin detemir in type 2 diabetes Home et al.

March 2015

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 South Korea Indonesia India Algeria

Detemir OGLD Detemir OGLD Detemir OGLD Detemir OGLD Detemir OGLD

Any complication
Time to event (years) 0.6 0.3 1.0 0.7 2.0 1.3 3.2 1.9 1.6 1.1
Severe vision loss
Incidence (% people) 16.4 23.1 7.2 9.7 5.5 8.8 7.8 12.1 8.3 11.0
Time to event (years) 12.2 9.9 11.0 9.9 13.9 12.6 16.0 14.8 13.3 12.3
End-stage renal disease
Incidence (% people) 8.6 20.0 5.1 10.3 2.9 7.7 3.6 11.2 5.0 9.6
Time to event (years) 13.6 11.4 11.4 10.4 14.1 13.0 16.6 14.8 13.9 13.0
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15

Myocardial infarction
Incidence (% people) 40.9 47.5 31.4 35.5 25.5 32.6 30.5 38.4 22.8 27.2
Time to event (years) 11.8 9.7 10.5 9.5 12.8 11.6 14.7 12.9 12.9 12.0
Ulcer
Incidence (% people) 27.4 28.0 28.6 30.2 16.1 18.3 18.4 22.3 17.4 19.2
Time to event (years) 12.0 10.2 9.9 8.9 12.7 11.7 15.1 13.4 12.9 12.0

OGLD, oral glucose-lowering drug; T2D, type 2 diabetes.

alone (Table 2). Overall, the reported reduction of cumu-
lative incidence ranged between 25% (Algeria) and 38%
(Indonesia) for severe vision loss, 48% (Algeria) and
68% (India) for end-stage renal disease, 2% (Mexico)
For personal use only.
(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

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 dia-
betes 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
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 scen-
ario, 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 add-
itional GP visits in the first year, had very little effect on
the ICERs (Table 5). However, the results were more sen-
sitive 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

234 Cost-effectiveness of insulin detemir in type 2 diabetes Home et al. www.informahealthcare.com/jme ! 2014 Informa UK Ltd
 Journal of Medical Economics Volume 18, Number 3 March 2015

analysis, the ICER, expressed as a fraction of GDP per

MXNDZD

MXNDZD

MXNDZD

MXNDZD
880,261

175,516

390,242

314,503
10,563
OGLD

2106

4683

3774
QALY, also remained cost-effective (53.0) after conduct-
ing sensitivity analyses for the cost of SMPG strips and
the cost of four GP visits after starting insulin detemir
Algeria

(Table 5).
MXNDZD

MXNDZD

MXNDZD

MXNDZD
1,315,170

636,139

404,847

274,185
Detemir

15,782

7634

4858

3290
Discussion
In this analysis, costs and outcomes associated with start-
ing insulin detemir in individuals with T2D on oral agents
MXNINR

MXNINR

MXNINR

MXNINR
340,325

204,439
79,366

56,519
6,126
OGLD

1428

1017

3680
alone were simulated over a 30-year time horizon using the
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15

previously validated CORE Diabetes Model, and were

found to be cost-effective in healthcare settings as different
India

as those in Algeria, Mexico, India, Indonesia, and South

MXNINR

MXNINR

MXNINR

MXNINR
Korea. To ensure local validity, we used locally specific
535,345

326,978

150,114
Detemir

58,254
9,636

5886

1048

2702

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). baseline clinical characteristics, and within-study surro-
gate and HRQoL outcomes, together with local costs
both for current therapies and long-term management of
complications. With this approach, longer-term dis-
226,000,000

154,066,000
29,208,000

42,726,000

counted costs were essentially neutral in Mexico,

MXNIDR

MXNIDR

MXNIDR

MXNIDR
22,600

15,407
OGLD

2920

4273

Indonesia, and South Korea, while the incremental costs

Table 3. Direct costs per patient of diabetes care simulated over 30 years with insulin detemir compared with OGLDs alone.

in Algeria and India, when calculated as the ratio to the

Indonesia

modeled QALY gain (ICER, and expressed as a fraction of

For personal use only.

GDP per capita), were cost-effective based on WHO

CHOICES criteria (Table 4). These outcomes are likely
233,311,000

129,676,000
59,913,000

43,722,000
MXNIDR

MXNIDR

MXNIDR

MXNIDR
Detemir

24,031

12,968

to reflect the major improvements in metabolic outcomes

5991

4372

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
MXNKRW

MXNKRW

MXNKRW

MXNKRW
43,406,000

39,862,000
2,196,000

1,348,000
39,933

36,673

QALY gains between countries (e.g., 5.0 for India, 1.0 for
OGLD

2020

1240

South Korea) is likely to be largely driven by the reduction

South Korea

in HbA1c reported in the A1chieve study; the average end-

of-study HbA1c for India was 7.2% (change from baseline:
2.1%), whereas the average end-of-study HbA1c for
MXNKRW

MXNKRW

MXNKRW

MXNKRW
43,422,000

37,039,000
4,963,000

1,420,000

South Korea was 7.9% (change from baseline: 1.5%).

Detemir

39,948

34,076
4566

1306

When modeled on a 30-year time horizon, the meta-

bolic changes are associated with a consistent reduction in
the incidence of major diabetes-related health outcomes
such as visual loss and myocardial infarction. Accordingly,
MXNMXN

MXNMXN

MXNMXN

MXNMXN
1,085,600

1,020,704

there is also a gain in life expectancy. Findings of improved

75,992

28,668

36,228

71,450
OGLD

2007

2536

metabolic outcomes in the short-term have been consist-

ent with insulin detemir in T2D in both RCTs and obser-
Mexico

vational studies, although the extent of the improvement

is often not as large in the RCTs as in the studies done in
OGLD, oral glucose-lowering drug.
1,078,195

routine clinical practice such as A1chieve5,13–15,17,19,21,23.

138,478

899,309
Detemir

MXN

MXN

MXN

MXN
75,474

40,408

62,952
9694

2829

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
Management costs

Complication costs
Treatment costs

of the relevant costs and outcomes. Indeed, extending the

Local currency

Local currency

Local currency

Local currency

time horizon to 50 years in the sensitivity analysis made

Total costs

very little difference to the final cost-effectiveness results.

USD

USD

USD

USD

Although data from RCTs are regarded as the ‘gold

standard’ with regard to informing policy-makers and

! 2014 Informa UK Ltd www.informahealthcare.com/jme 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 South Korea Indonesia India Algeria

30-year ICER (cost per QALY gained) (base case)

Local currency 2887 MXN (dominant) 15,139 KRW 3,995,329 IDR 39,214 INR 368,200 DZD
USD 222 14 415 707 4625
GDP fraction 0.02 0.00 0.12 0.48 0.88
Incremental cost 7404 16,231 KRW 7,310,250 IDR 195,020 INR 434,909 DZD
Incremental QALY 2.57 1.07 1.83 4.97 1.18
Incremental LE (years) 1.19 0.60 0.61 0.90 0.50
1-year ICER (cost per QALY gained)
Local currency 62,952 MXN 4,273,409 KRW 22,920,222 IDR 58,454 INR 617,658 DZD
USD 4835 3935 2381 1054 7758
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15

GDP fraction 0.48 0.18 0.68 0.71 1.48

Incremental cost 9443 MXN 269,225 KRW 2,544 145 IDR 18,822 INR 39,530 DZD
Incremental QALY 0.15 0.06 0.11 0.322 0.064
Incremental LE (years) – – – – –

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 rou-
tine clinical practice. In reality, the short-term metabolic
For personal use only.
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

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 ana-
lysis, 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 dif-
ferences in the gain of life-years free of complications
between countries, and because the incremental health-
care costs varied widely between countries, it is not
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 contin-
ued baseline treatment was available for modeling. Other
insulins were studied in A1chieve, and similar short-term
clinical outcomes were reported, but the populations allo-
cated 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 observa-
tional study, we can only assess the cost-effectiveness asso-
ciated 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 pres-
sure, suggests that starting the insulin analog was an oppor-
tunity for enhanced lifestyle modification.
As a limitation, there was a lack of published resources
specific to the studied populations in terms of costs.

236 Cost-effectiveness of insulin detemir in type 2 diabetes Home et al. www.informahealthcare.com/jme ! 2014 Informa UK Ltd
 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 QALY Incremental Incremental Increased LE ICER

cost QALY (years)

Mexico (MXN) (MXN) (MXN)

30-year analysis
Base case 1,078,195 8.56 7404 2.57 1.19 Dominant
50-year time horizon 1,085,111 8.57 2542 2.57 1.21 Dominant
No HbA1c deterioration 1,019,232 8.85 35,599 2.57 1.10 Dominant
Median treatment effect (HbA1c) 1,081,730 8.50 3869 2.51 1.13 Dominant
Quartile 1 treatment effect (HbA1c) 1,141,864 8.00 56,265 2.01 0.56 28,039
Including costs of SMPG strips 1,106,004 8.56 20,405 2.57 1.19 7,955
4 additional visits in the first year after 1,081,108 8.56 4492 2.57 1.19 Dominant
starting insulin detemir
2 GP visits every year after starting 1,091,736 8.56 6136 2.57 1.19 2392
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15

insulin detemir
Average global EQ-5D 1,078,195 8.83 7404 2.84 1.19 Dominant
Insulin started after 5 years 1,078,195 8.56 21,695 1.30 0.72 Dominant
1-year analysis
Base case 12,273 0.87 9443 0.15 – 62,952
Including costs of SMPG strips 14,737 0.87 11,907 0.15 – 79,382
4 additional visits after starting 15,273 0.87 12,443 0.15 – 82,952
insulin detemir
South Korea (KRW) (KRW) (KRW)
30-year analysis
Base case 43,422,013 6.55 16,231 1.07 0.60 15,139
50-year time horizon 43,517,627 6.55 70,038 1.07 0.60 65,323
No HbA1c deterioration 41,469,854 6.75 8346 1.08 0.58 7726
Median treatment effect (HbA1c) 43,787,426 6.46 381,644 0.97 0.48 392,045
Quartile 1 treatment effect (HbA1c) 45,254,759 6.20 1,848,977 0.71 0.17 2,591,132
Including costs of SMPG strips 44,815,361 6.55 1,409,578 1.07 0.60 1,314,779
For personal use only.

4 additional visits in the first year 43,459,422 6.55 53,619 1.07 0.60 50,013
after starting insulin detemir
2 GP visits every year after starting 43,606,209 6.55 200,406 1.07 0.60 186,928
insulin detemir
Average global EQ-5D 43,422,034 7.64 16,231 2.16 0.60 7528
Insulin started after 5 years 43,422,034 6.55 281,319 0.59 0.39 479,504
1-year analysis
Base case 508,241 0.84 269,225 0.06 – 4,273,409
Including costs of SMPG strips 650,922 0.84 411,907 0.06 – 6,538,200
4 additional visits after starting 546,751 0.84 307,735 0.06 – 4,884,679
insulin detemir
Indonesia (IDR) (IDR) (IDR)
30-year analysis
Base case 233,310,512 8.59 7,310,250 1.83 0.61 3,995,329
50-year time horizon 235,955,583 8.62 8,788,811 1.86 0.65 4,719,843
No HbA1c deterioration 227,093,595 8.80 8,598,181 1.83 0.56 4,693,507
Median treatment effect (HbA1c) 235,598,240 8.55 9,597,977 1.79 0.58 5,376,238
Quartile 1 treatment effect (HbA1c) 243,371,064 8.28 17,370,801 1.52 0.32 11,412,226
Including costs of SMPG strips 271,009,642 8.59 45,009,379 1.83 0.61 24,599,335
4 additional visits in the first year 233,844,469 8.59 7,844,231 1.83 0.61 4,287,170
after starting insulin detemir
2 GP visits every year after starting 235,600,622 8.59 9,600,384 1.83 0.61 5,246,975
insulin detemir
Average global EQ-5D 233,310,489 9.31 7,310,250 2.55 0.61 2,865,537
Insulin started after 5 years 233,310,489 8.59 2,355,504 0.85 0.35 Dominant
1-year analysis
Base case 5,232,238 0.96 2,544,145 0.11 – 22,920,222
Including costs of SMPG strips 8,524,538 0.96 5,836,445 0.11 – 52,580,582
4 additional visits after starting 5,782,238 0.96 3,094,145 0.11 – 27,875,177
insulin detemir
India (INR) (INR) (INR)
30-year analysis
Base case 535,345 12.72 195,020 4.97 0.90 39,214
50-year time horizon 545,770 12.81 200,378 5.03 0.94 39,819
No HbA1c deterioration 515,254 13.05 200,589 4.98 0.73 40,323
Median treatment effect (HbA1c) 542,774 12.49 202,449 4.75 0.72 42,648
Quartile 1 treatment effect (HbA1c) 552,122 12.19 211,797 4.44 0.48 47,660
Including costs of SMPG strips 618,761 12.72 278,436 4.97 0.90 55,987
4 additional visits in the first year 536,122 12.72 195,796 4.97 0.90 39,370
after starting insulin detemir
2 GP visits every year after starting 537,916 12.72 197,591 4.97 0.90 39,731
insulin detemir
(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.
Cost QALY Incremental Incremental Increased LE ICER
cost QALY (years)

Average global EQ-5D 535,345 10.81 195,020 3.07 0.90 63,511

Insulin started after 5 years 535,345 12.72 71,697 2.02 0.48 35,536
1-year analysis
Base case 25,435 0.79 18,822 0.32 – 58,454
Including costs of SMPG strips 31,924 0.79 25,311 0.32 – 78,606
4 additional visits after starting 26,235 0.79 19,622 0.32 – 60,938
insulin detemir
Algeria (DZD) (DZD) (DZD)
30-year analysis
Base case 1,315,170 8.02 434,909 1.18 0.50 368,200
50-year time horizon 1,315,951 8.02 435,554 1.18 0.50 369,445
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15

No HbA1c deterioration 1,311,148 8.23 441,662 1.18 0.46 375,048

Median treatment effect (HbA1c) 1,312,359 7.99 432,097 1.14 0.46 378,181
Quartile 1 treatment effect (HbA1c) 1,315,011 7.65 434,750 0.81 0.11 539,454
Including costs of SMPG strips 1,498,414 8.02 618,152 1.18 0.50 523,336
4 additional visits in the first year 1,316,626 8.02 436,365 1.18 0.50 369,433
after starting insulin detemir
2 GP visits every year after starting 1,317,461 8.02 437,200 1.18 0.50 370,140
insulin detemir
Average global EQ-5D 1,315,170 9.28 434,909 2.44 0.50 178,144
Insulin started after 5 years 1,315,170 8.02 176,584 0.57 0.30 309,853
1-year analysis
Base case 55,529 0.83 39,530 0.06 – 617,658
Including costs of SMPG strips 71,524 0.83 55,526 0.06 – 867,588
4 additional visits after starting 57,029 0.83 41,030 0.06 – 641,096
insulin detemir

GDP, gross domestic product; GP, general practitioner; ICER, incremental cost-effectiveness ratio; LE, life expectancy; OGLD, oral glucose-lowering drug; QALY,
For personal use only.

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 lack-
ing, and by asking them to comment on the obtained esti-
mates, 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 asso-
ciated with the management of diabetes-related complica-
tions. 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
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 ther-
apy. 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 dif-
ference to cost-effectiveness. Similarly, insulin therapy
may require further SMPG11, but this did not substantially
affect overall costs either. To further address the hypothet-
ical 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 health-
care resources. A range of sensitivity analyses supported

238 Cost-effectiveness of insulin detemir in type 2 diabetes Home et al. www.informahealthcare.com/jme ! 2014 Informa UK Ltd

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
Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 06/23/15
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 assist-
ance with analyses, funded by Novo Nordisk.
For personal use only.
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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