Diabetes Care In Indonesia Role of GLP 1

Analog

Pradana Soewondo
Department of Internal Medicine
Faculty of Medicine University of IndonesiaCipto Mangunkusumo National Referral Hospital
Jakarta, Indonesia

Overview
Results of IDMPS Indonesia
Perkeni Guidelines and Awareness

Survey
Glucagon like peptide 1 analog
Conclusion

IDMPS
Indonesia
715 DM patients
686 met inclusion/exclusion
criteria
12 T1DM and 674 T2DM
Location : 85% urban vs 15%

rural
Age : mean 55.16 (SD 10.20)
years
BMI
Sex : female
54.6% vs male
52.6
60
50 45.4%
34.3
40
30

BMI : mean 24.78 (SD 4.02)

20
8.6
3.5 2
10
1.1
kg/m
0
<18.5

18.5-25

25-30

30-35

>35

90

76.7

80
70
60
50
40
30

16.8

20
10

6.4
0.1

<40 40-65 65-85 >85

Age Group

IDMPS Indonesia

40.6

HbA1c
Measurement

59.4
A1c Measurements
No A1cMeasurements

OGLD
HbA1c
OGLD Insulin
+
Group
Insulin
<7%
14.3
32.9
15.8
HbA1c
8.49
8.12
8.58
Mean (SD) (1.42) (2.12)
(2.61)

Diet +
Exerci Total
se
44.4
30.5
7.04
8.27
(1.18) (2.19)
IDMPS Indonesia

Comorbidities and
Complications Type 2
Variable
Hypertension
Yes with treatment
Yes but no treatment
No hypertension
Dislipidemia
Yes with treatment
Yes but no treatment
No dislipidemia
Late complication
At least one
No complication

Lifestyle

OGLD

Insulin +

Total

8 (38.1)
0
13 (61.9)

230 (44.2)
17 (3.3)
273 (52.5)

59 (45.4)
5 (3.8)
66 (50.8)

297 (44.3)
22 (3.3)
352 (52.5)

8 (40.0)
4 (20.0)
8 (40.0)

179 (42.6)
36 (8.6)
205 (48.8)

53 (50.0)
12 (11.3)
41 (38.7)

240 (44.0)
52 (9.5)
254 (46.5)

9 (69.2)
4 (30.8)

290 (70.6)
121 (29.4)

97 (85.8)
16 (14.2)

396 (73.7)
141 (26.3)

Most diabetic patients have at least one late diabetic complication

Diabetic Complications
60

Microangiopathy >>
Macroangiopathy

54

50

Re nopathy
Neuropathy
Proteinuria

40
30

Dialysis

33.4

Foot Ulcer
26.5

Amputa on
Angina
MCI

20
10.9

8.7
10
0.5
0

7.4
1.3

5.3

2.7

5.3

Heart Failure
Stroke
PAD
IDMPS Indonesia

Resource Use
Variable
Specialty
GPs/ internists
Endocrinologists
Follow up in the last 3
months
By GPs/ internists
Followed up
None
By endocrinologists
Followed up
None

Type 2

Lifestyle

OGLD

Insulin +

Total

13 (61.9)
8 (38.1)

387 (74.0)
136 (26.0)

71 (54.6)
59 (45.4)

471 (69.9)
203 (30.1)

1 (33.3)
2 (66.7)

105 (60.7)
68 (39.3)

23 (47.9)
25 (52.1)

129 (57.6)
95 (42.4)

13 (100.0)
0

332 (95.4)
16 (4.6)

96 (98.0)
2 (2.0)

446 (96.1)
18 (3.9)

Indirect Cost
Variable
Lifestyle
Working productivity
Unemployed
Normal work
Sick leave
Unable to work
Hospitalized
Yes
No
Mean (SD)
Median

Type 2
OGLD
Insulin +

Total

13 (61.9)
8 (38.1)
0
0

283 (54.2)
195 (37.4)
32 (6.1)
12 (2.3)

63 (48.5)
31 (23.8)
32 (24.6)
4 (2.3)

359 (53.3)
234 (34.8)
64 (9.5)
16 (2.4)

2 (12.5)
14 (87.5)
2.5 (2.1)
1.0

41 (12.5)
288 (87.5)
1.2 (0.4)
1.0

26 (28.0)
67 (72.0)
1.0 (0.2)
2.5

69 (15.8)
369 (84.2)
1.1 (0.5)
1.0

Only 34.8% of diabetic patients had normal work

Education Session

Variable
Lifestyle
Diabetes education
Given
None
Mean (SD)
Median

8 (40.0)
12 (60.0)
6.8 (4.7)
3.0

Type 2
OGLD
168 (34.6)
317 (65.4)
4.1 (3.3)
3.0

Insulin +

Total

49 (41.2)
70 (58.8)
4.3 (3.9)
7.0

225 (36.1)
399 (63.9)
4.2 (3.5)
3.0

Only 36.1% of diabetic patients had formal diabetic education session

% Target Achievement

70

58

60
50

44

40

40

37.4

34.45

30

16

20
10
0

China

South Korea

Panama

Egypt

Indonesia DIabCare-Indonesia

Conclusion
DIABETES
Chronic condition with comorbidities and
complications
Huge resource use and significant cost
ACTION
early diagnosis
prompt treatment
effective metabolic control
screening for diabetic complications

The
Indonesian Society of
Endocrinologist's
Diabetes Mellitus
National Clinical
Practice Guidelines

DM

PERKENI Guideline 2011

Lifestyle
Modification

Phase-I
Lifestyle
Modification
+
OAD Monotherapy

Phase-II

Lifestyle
Modification
+
2 OADs
Combination

Alternative :
Insulin not available
Patient preference
Glucose control not
optimal

Notes :
Fail : not achieving A1c target <7% after 2-3
months of treatment.
(A1c = average blood glucose conversion, ADA
2010)

Lifestyle
Modification
+
3 OADs
Combination

Phase-III

Lifestyle
Modification
+
2 OADs
Combination
+
Basal insulin

Intensive Insulin

HbA1c Level
7-8%

Lifestyle
Modification

Lifestyle
Modification

PERKENI Guideline 2011

<7%

+
Monotherapy
Met, SU, AGI,
Glinid, TZD,
DPP-IV

8-9%

>9%

9-10%

>10%

Lifestyle
Modification
+
2 OADs
Combination
Met, SU, AGI,
Glinid, TZD,
DPP-IV

Notes :
Fail : not achieving A1c target <7% after 23 months of treatment.
(A1c = average blood glucose conversion,
ADA 2010)

Lifestyle
Modification
+
3 OADs
Combination
Met, SU, AGI,
Glinid, TZD,
DPP-IV

Lifestyle
Modification
+
2 OADs
Combination
Met, SU, AGI,
Glinid, TZD
+

Lifestyle
Modification

Basal Insulin

+
Intensive
Insulin

Awareness, agreement and adherence of

physicians to
type 2 diabetes guideline in Indonesia
Indah S. Widyahening, Geert JMG van der Heijden, Pradana

Soewondo, Yolanda van der Graaf

Background

Diabetes has been recognized as an emerging health

problem in Indonesia. While guideline on the management
of type 2 diabetes mellitus (T2DM) was available for almost
two decades, 68% of the patients were in poor control.
Aim
To study the awareness, agreement and adherence of
physicians to T2DM guideline in Indonesia.
Methods
Questionnaire survey of General Practices (GPs) regarding
recommendations in theIndonesian T2DM guideline based
on the awareness-to-adherence model of behavioral
change.
(Unpublish data)

Characteristics

n (%)

Media
n

Minmax

Age (n=399)

43 years 22-73 years

Year of practice (n=383)

15 years

Gender (n=399)
Male / Female

126 (32) / 273

(68)

Practice type (n=392)

Solo practice

208 (53)

Private clinic

64 (16)

Public health center

96 (22)

Private hospital

20 (5)

Public hospital (non academic)

8 (2)

Academic hospital

6 (2)

Practice location (n=359)

Jakarta

119 (33)

Outside Jakarta but within Java

island

127 (35)

0-45 years

Characteristics
Participation in DM training
(n=367)
Yes
Number of DM patients seen in
a week (n=343)
Proportion of DM patients
among all patients seen
(n=381)
<10%
10-30%
>30%
Awareness to DM consensus
(n=383)
Never know
Heard but never had
Had but never read
Read and implement

n (%)

Media
n

Minmax

1-120

234 (64)

243 (64)
117 (31)
21 (5)

43 (11)
138 (36)
78 (20)
124 (33)

Guidelines recommendations assessed in

the questionnaire.
Screening for T2DM should be performed to all patients with

any of the risk factor listed in the guidelines.

In patients with classic DM symptoms, one random blood
glucose test with result >200 mg/dL is enough to confirmed
the diagnosis.
For newly diagnosed patient, management should be started
with meal planning and exercise for 2-4 weeks.
SUis the drug of choice for normal and underweight patients.
Most patients should achieve Fasting Blood Glucose of <100
mg/dL and 2-hour post-prandial Blood Glucose of <140
mg/dL.
Blood pressure should be reduced to below 130/80 mmHg.
Statin should be prescribed to people with T2DM who are
over 40 years old or have CVD risk.

GPs' awareness of, agreement with, adoption of, and

adherence to selected recommendations of the Indonesian
T2DM guidelines

Conclusion
Despite high awareness GPs may not adopt

recommendations let alone adhere to it.

The updating process of the guideline should
also consider some effective means to
disseminate it and include a system to ensure
its adherence.
This also pertains to those who plan to
develop guidelines.
Further research will be needed to identify
the barriers to adhere to each of the
recommendation.

The unmet need in type 2 diabetes

PPG, postprandial glucose

Over time, glycaemic control deteriorates

*Diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/L
ADA clinical practice recommendations. UKPDS 34, n=1704
UKPDS 34. Lancet 1998:352:85465; Kahn et al (ADOPT). N Engl J Med 2006;355:242743

Most therapies result in weight gain over time

*Conventional treatment (

); diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/L

UKPDS 34. Lancet 1998:352:85465; Kahn et al (ADOPT). N Engl J Med 2006;355:242743

Risk of complications
Benefits of lowering hemoglobin HbA1c

Relative Risk
of complications

16
12
8
4
0

6
Average Glucose
mg/dl

120

150

Hemoglobin HbA1c (%)

10

11

12

180 from210
240
270
300
Adapted
UKPDS 33:
Lancet 1998;352:837-853.
Adapted from DCCT Study Group. N Engl J Med
1993;329:977.

Impact of poor compliance

Poor compliance with treatment for chronic diseases is a

worldwide problem of considerable magnitude

Around 50% compliance with long-term therapy for

chronic illnesses in developed countries

Compliance rates are expected to be lower

in developing countries

WHO. Compliance to long-term therapies: evidence for action. Geneva: WHO,

2003.

Consequences of poor compliance

Lack of compliance leads to:1
Reduction in effectiveness of treatment
Poor health outcomes and increased

health care costs

Reduced quality of life
Increasing the effectiveness of adherence interventions may

have a far greater impact on the health of the population than

any improvement in specific medical treatments 2

1. WHO. Compliance to long-term therapies: evidence for action. Geneva: WHO, 2003;
2. Haynes RB et al. The Cochrane Database of Systematic Reviews 2002, Issue 2.

Compliance: influenced by several factors

Compliance is frequently compromised by more than one

barrier
Social and economic factors
Healthcare team/system
Condition-related factors
Therapy-related factors
Patient-related factors

WHO. Compliance to long-term therapies: evidence for action. Geneva: WHO, 2003.

Patients need support, not blame

Patient-related factors not necessarily

the biggest barrier to compliance

focus on provider/health system-related

determinants (e.g. feedback, short consultations etc.)

Support patients in their efforts at

self-management
More effective interventions are essential

WHO. Compliance to long-term therapies: evidence for action. Geneva: WHO, 2003.

Poor compliance: an important medical problem

Poor or erratic compliance is most common when:
The treatment is preventive
The patient is frequently asymptomatic
Therapy is long-term
Therapy is associated with significant side effects

Rand C. Am J Cardiol 1993; 72: 68-74D.

The Cost of Diabetes

Direct Costs Personal
Drugs, supplies,
insurance

Indirect Costs
Loss of productivity

Direct Costs healthcare

System
Treatment and
rehabilitation
Hospital and healthcare
professional services
Products, supplies, tests
Hospital admissions

Premature retirement
Premature mortality
Pain, anxiety and inconvenience

decrease quality of life

Work discrimination
Negative effect on relationships,

mobility and leisure activities

WHO Fact Sheet 2012

Economic burden of type 2 diabetes continues to rise in

both developed countries and emerging markets
Direct costs for diabetes-related care are projected to reach USD 376
billion globally in 2010 and USD 490 billion by 2030
Estimated 2010 Total Costs
for Diabetes (US$ Bn)

Estimated 2010 Cost

per Patient (US$)

12/25/16

12
/2
5/
16

12
/2
5/
16

12/25 12/25/1
/16
6

12/2
5/16

Source: IDF Diabetes Atlas 2009 www.eatlas.idf.org

12/2
5/16

12
/2
5/
16

12
/2
5/
16

12/25 12/25/1 12/2

/16
6
5/16

12/2
5/16

Diabetes-related healthcare expenditures

reakdown of Direct Diabetes

osts per Patient

12/25/16

12/25/16

Breakdown of
Pharmacotherapy for
Diabetes Patients
12/25/16%

12/25/16

12/25/16%

12/25/16

12/25/16% 12/25/16
12/25/16%

12/25/16
42%

12/25/16

12/25/16
12/25/16

Source: Jonsson B et al. Diabetologia 2002; 45: S5-S12.

26%

12/25/16

Cardiovascular
and lipid lowering

12/25/16

The Cost of Diabetes

For most countries, largest

single diabetes expenditure is

hospital admissions for the
treatment of long-term
complications (e.g. heart
disease, stroke, kidney failure,
foot problems)
World Diabetes Foundation 2012

Diabetic Cost : ASKES Data

25

23

20
14

15
10

5
0

ASKES

126.104 pts

258.208 pts

384.312 pts

Million US$
Without Complications
Data
Total

With Complications

Annual cost for each diabetes patient

Without Complications + 40 US$
258.208 patientsWith Complications + 900 US$

Diabetic Cost : ASKES Data

US$
1000
900
800
700
600
500
400
300
200
100
0

900

40

US$

DM Direct Cost in Secondary- Tertiary

at Yogyakarta Hospital - 2004
Direct cost for OAD treatment USD 22
OAD +insulin USD 63
the cost of diabetes related

complications (hypertension and

retinopathy) USD 84
Cost for initial comprehensive diagnosis
of DM USD 150
Cost component on drugs 59.5%
Diabetes-related complications cost

31%

Short and long-term cost-effectiveness of

initiating Biphasic insulin aspart 30 in insulinnave patients with type 2 diabetes
Objectives:
To assess the cost-effectiveness (CE) of initiating BIAsp 30 therapy
OADs in patients with T2D in countries in different economic
circumstances based on observational data gathered in routine clinical
practice.
Methods:
The CE analysis included A1Chieve subjects initiating BIAsp 30 in Saudi
Arabia (n=901), India (n=7,546), Indonesia (n=153), in Malaysia based
on patients in 4 ASEAN countries (n=430) and in 3 countries in NorthWest Africa (n=279).
Data were collected on clinical effectiveness, adverse events, and patient
reported outcomes using the EQ-5D questionnaire.
CE analyses used the IMS CORE diabetes model with 1 and 30 year time
horizons, with country-specific costs for complications and therapies and
background mortality rates.
Incremental cost-effectiveness ratios (ICER) are expressed as cost/QALY in
local currencies, USD and in fractions of local GDP per capita based on
initiating BIAsp 30.
Cost Effectiveness was pre-defined as <3*GDP.

Unpublish data

Tabel 1. Treatment Effect

Country
Saudi Arabia

Treatmen
Patient # t effect
P value
(HbA1c)

EQ5D
effect

P value

901

-2.7

<0.001

0.1434

NA

7,546

-1.9

<0.001

0.312
(0.294)

<0.001

Indonesia

153

-2.9

<0.001

0.154
(0.197)

<0.001

Algeria,
Tunisia,
Morocco

279

-2.4

<0.001

0.152
(0.254)

<0.001

<0.001

0.148
(0.212)

<0.001

India

ASEAN

430

-2.7

Tabel 2. Baseline Estimates

1 year ICER ( cost)/( QoL)
Country

Saudi Arabia

India

Currency/Cost
setting

SAR

INR

30 year, ICER, QALE

In currency per
QALY gained

Fraction of
GDP per capita

In currency per
QALY gained

10,740.71

0.14 (Highly
cost-effective)

-3,004.00

35,182.37

0.43 (Highly
cost- effective)

20,516.00

Indonesia

IDR

40,487,476.83

1.20 (Costeffective)

15,710,332.00

Algeria,
Tunisia,
Morocco

DZD

246,422.17

0.73 (Highly
cost- effective)

155,659.00

ASEAN

IDR

52,620,159.53

1.28 (Costeffective)

25,613,537.00

Fraction of
GDP per
capita
-0.04(Domi
nant)
0.25
(Highly
costeffective)
0.47
(Highly
costeffective)
0.46
(Highly
costeffective)
0.62
(Highly
costeffective)

Tabel 3. Sensitivity Analysis

Sensitivity analysis in fraction of GDP per capita
2 additional
GP visits in
the first
year after
switch

Currency
/Cost
setting

30 years

No HbA1c
deterioration

Saudi
Arabia

SAR

-0.03
(robust)

-0.04
(robust)

-0.03
(robust)

0.02 (costeffective)

-0.04
(robust)

-0.04
(robust)

0.01 (costeffective)

India

INR

0.25
(robust)

0.25
(robust)

0.28
(robust)

0.67
(robust)

0.25
(robust)

0.25
(robust)

0.32
(robust)

Indonesia

IDR

0.49
(robust)

0.48
(robust)

0.49
(robust)

1.31
(robust)

0.47
(robust)

0.47
(robust)

0.62
(robust)

Algeria,
Tunisia,
Morocco

DZD

0.46
(robust)

0.47
(robust)

0.49
(robust)

0.90
(robust)

0.46
(robust)

0.46
(robust)

0.56
(robust)

ASEAN

IDR

0.65
(robust)

0.62
(robust)

0.65
(robust)

1.35
(robust)

0.62
(robust)

0.63
(robust)

0.83
(robust)

Country

Including
costs of
SMBG
strips

1 additional
GP visit in
the first
year after
switch

Median
treatment
effect
(HbA1c)

Q1
treatment
effect
(HbA1c)

Conclusion:
Initiating BIAsp 30 in T2D as
performed in the A1chieve study was
found to be cost-effective across all
country settings based on a 1 and 30
year time horizon.

Ideal intervention would directly address key elements

of disease progression

Current Available Treatments:

Unmet Needs in T2DM Management

Insulin Resistance
(Impaired insulin action)

Pancreatic Islet Dysfunction

Inadequate
glucagon
suppression
(-cell
dysfunction)

Metformin

TZDs

Insufficient
Insulin
secretion
(-cell
dysfunction)

Progressive
decline of -cell
function

Sulfonylureas
Glinides

DPP-4 Inh
Weight of red arrows reflects the degree to which DPP-4 inhibitors influence the disease mechanisms.
DPP-4=dipeptidyl peptidase-4; TZD=thiazolidinedione; T2DM=type 2 diabetes mellitus.
Adapted from DeFronzo RA. Br J Diabetes Vasc Dis 2003;3(Suppl1):S24S40

Efficacy as Add-on to Metformin

Comparable efficacy of DPP4i class with lesser hypoglycemia &
weight gain
HbA1c change

SU
s
Adapted from Phung OJ et al. JAMA 2010;303:1410

Efficacy as Add-on to Metformin (Low

dose/High dose)
Additional efficacy benefit

HbA1c change from Baseline to Endpoint ; Mean Baseline HbA1c ~8.6 %

Vilda 50 mg bid Vilda + low dose met (50/500 mg bid)

Bosi E et al. Diabetes Obes Metab 2009;11:506

Met 1000 mg bid Vilda + high dose met (50/1000 mg bid)

Hypoglycemia in T2DM
Risk factors and at-risk groups
AT-RISK GROUPS
Renal impairment1
Older people1
Lower HbA1c1
Prior hypoglycemia1
Long-duration diabetes1
Hypoglycaemia
unawareness1

RISK FACTORS
Exercise1
Irregular eating habits1
Alcohol1
Periods of fasting, e.g.
Ramadan2
Use of insulin and
sulfonylureas3

Amiel SA et al. Diabet Med 2008;25:24554; 2Salti L et al. Diabetes Care 2004;27:230611;
3
Nathan DM et al. Diabetes Care 2009;32:193203

Hypoglycaemia in the Elderly

The elderly population is growing and
there is a high prevalence of type 2
diabetes mellitus in this group
17.6%

Standardized prevalence
of diagnosed diabetes
by age group2

14.9%

Severe hypoglycemia
accounts for almost
20% of all
hospitalizations for
T2DM in the elderly

7.9%

2.1%
0.2%
12-19

20-39

40-59

Worldwide, the
elderly population in
developed regions
will nearly double by
20501

60-74

75

Age (years)
Greco D et al. Exp Clin Endocrinol Diabetes 2010;118:2159
Adapted from Chelliah A, Burge MR. Drugs Aging 2004;21:51130

1. UN Report 2004: World Population to 2300

2. Adapted from Cowie CC et al. Diabetes Care 2009;32:28794

Hypoglycaemia rates as Add-on to Metformin:

Lower hypoglycemia with DPP4i versus other
OADs
Hypoglycemia RR

Adapted from Phung OJ et al. JAMA 2010;303:1410

48

Vildagliptin vs Glimepiride as add-on to metformin:

As effective as Met+SU on HbA1c reduction with less weight gain
and hypoglycaemia at 52 weeks
Change in body weight

Mean HbA1c (%)

7.5
7.3
7.1

NI: 97.5%
CI (0.02, 0.16)

6.9

0.4%

6.7
0.5%
6.5

Adjusted mean change

in body weight (kg)
from BL

Mean HbA1c reduction

(BL mean
~88.8kg)

P <0.001; adjusted
mean change from BL to
Week 52,
between-treatment
difference and P value
were from an ANCOVA
model containing terms
for treatment, baseline
and pooled centre.
BL=baseline;
CI=confidence interval
NI=non-inferiority; aPer
protocol population ;
b
Safety population.
c
Grade 2 or suspected
grade 2 events.
*

n = 1117 1071

0.0
4

Incidence of hypoglycaemia

8 12 16 20 24 28 32 36 40 44 48 52 56

Time (weeks)

Duration: 52 weeks, add-on to

metformin: vildagliptin vs glimepiride

Incidence (%)

Vildagliptin 50 mg twice daily + metformin

Glimepiride up to 6 mg once daily + metformin

Number of
hypoglycaemic
events
13891383
554

Patients with
1 hypos (%)
n =1389 1383

Number of severe
hypoglycaemic events
c
1389 1383

16.2

1.7

No. of
events

No. of events

-8 -4

*
39

Ferrannini E et al. Diab Obes Metab 2009; 11: 157166

Vildagliptin add-on metformin

Powerful 1.1% reduction in HbA1c in the very elderly (75
years) with no hypoglycaemia or weight change

HbA1c1
n=
BL (%)=

25
8.5

0.0

Body weight1
n=
BL (%)=

25
82.8

-0.4

-0.1

-0.6
-0.8

-1.2

31

0.0

-0.2

-1.0

Hypoglycaemia2

-0.2

-0.2

Any events, n
(%)

0
(0.0%)

Severe events, n
(%)

0
(0.0%)

-1.1
-0.3

Overall AEs, drug-related AEs and SAEs were all reported with a lower frequency in elderly patients receiving vildagliptin (133.9, 14.5 and 8.8 events per 100 SYE, respectively)
than in elderly patients receiving comparators (200.6, 21.8 and 16.5 events per 100 SYE, respectively), and the incidence of discontinuations due to AEs was similar in the 2
treatment groups (7.2 vs 7.5 events per 100 SYE, respectively). The incidences of AEs, drug-related AEs, SAEs and discontinuations due to AEs were overall comparable
between younger and older patients. The most notable difference was a higher incidence of SAEs in the comparator group in patients 75 years vs <75 years.
1. Efficacy pool: all randomised, double-blind, controlled, parallel-group studies with duration 24 weeks and with patients 75 years. Only includes studies with the approved
dose of 50 mg twice daily. 2. Safety pool: a pool of 38 Phase II and III studies (monotherapy and add-on therapy).
*P <0.05 vs baseline (within group). AEs=adverse events; bid=twice daily; BL=baseline; HbA1c=haemoglobin A1c; SAEs=serious adverse events.

Adapted from Schweizer A et al. Diabetes Obes Metab 2011;13:5564

Vildagliptin as add-on therapy to dual combination of

metformin and glimepiride is efficacious without relevant
increase in weight and with a low incidence of hypoglycemia
HbA1c Change from BL to EP
BL =
N=

8.75
152

8.80
160

FPG Change from BL to

EP
BL =

9.34

9.52

N=

152

160

Hypoglycemic Events#

N=

157

160

*
Weight by Visit

*
73.7
72.3
Vilda 50 mg bid + Met + Glim
Placebo + Met + Glim
Between-treatment difference
*P<0.001. FAS was used for HbA1c and FPG analyses. Safety set was used for hypoglycemia and weight analyses. # Hypoglycemic events are defined as
symptoms suggestive of hypoglycemia with a plasma glucose measurement <3.1 mmol/L. BL, baseline; EP, endpoint; FPG, fasting plasma glucose; FAS,
full analysis set; Glim, glimepiride; HbA1c, glycosylated hemoglobin A1c; Met, metformin; SE, standard error; Vilda, vildagliptin; Wk, week.
Study 23152, Novartis Data on file, PT-Table 14.2-2.1; PT-Table 14.2-2.3; PT-Table 14.3.1-2.3; PT-Table 14.3-3.1.

51

Cost-effectiveness of Vildagliptin

The Sheffield type 2 Diabetes Model - Methods

The analysis uses the Novartis 24-week 2354 study results comparing
vildagliptin 50mg BID to pioglitazone 30mg qd.
The Sheffield Type 2 Diabetes Model, a patient-level disease
management model, simulates use of therapies, clinical events,
treatment of complications and mortality.
Costs, including the 1.13 vildagliptin daily price and 1.20 for
pioglitazone, and quality-of-life (QoL) effects, including those related to
complications and weight effect of therapies, were aggregated to
obtain the incremental cost per QALY.
Uncertainty around key parameters, such as weight effects and longterm HbA1c trends, was explored using probabilistic sensitivity
analysis and scenarios

Brennan A et al. Value Health 2008;11:A501 [Poster PDB19]

The Sheffield type 2 Diabetes Model

Total costs are obtained by adding the costs of therapy, one-off treatments of complications,
and on-going treatment.
The health benefit, the incremental quality-adjusted life-years, is obtained by applying quality
of life measures to the time spent in the various diabetic health states.
Cost effectiveness estimates for potential interventions are obtained by dividing the total costs
by the incremental QALYs
Brennan A et al. Value Health 2008;11:A501 [Poster PDB19]

Vildagliptin is a cost-effective alternative vs. Pioglitazone

Vildagliptin vs. Pioglitazone male, BMI 30

No Complications

With Complications

Vildaglilpt
in

Pioglitazo
ne

Net

Vildaglilpt
in

Pioglitazon
e

Net

UKPDS QALYS

8.561

8.590

-0.029

8,353

8,378

-0.025

Total QALYs

8.468

8.479

-0.011

8,262

8,269

-0.007

Direct drug cost

()

5371

5824

-453

5220

5665

-445

15,731

16,180

-449

16,309

16,756

-446

Total cost ()
ICER ()

39,84
6

66,79
9

In summary, the gliptins and the glitazones appear roughly equivalent in glycaemic
effect, but the former have an advantage in avoidance of weight gain, which,
together with their lower (at present) costs may give them an edge.

Waugh N et al. Health Technol Assess. 2010 Jul;14(36):1-248

Vildagliptin is a cost-effective alternative vs. Pioglitazone

Vildagliptin vs. Pioglitazone female, BMI 30

No Complications

With Complications

Vildaglilpt
in

Pioglitazo
ne

Net

Vildaglilpt
in

Pioglitazon
e

Net

UKPDS QALYS

9.428

9.427

0.000

9.715

9.176

-0.001

Total QALYs

9.328

9.310

0.019

9.078

9.061

0.017

Direct drug cost

()

5824

6265

-441

5646

6082

-437

15,959

16,502

-543

16,581

17,112

-531

Total cost ()
ICER ()

Dominant

Waugh N et al. Health Technol Assess. 2010 Jul;14(36):1-248

Domin
ant

 Long-term modelling:
Long-term HbA1c changes
Long-term weight changes
Relative Risk of heart failure

The expected differences in lifetime costs and QALYs between

vildagliptin and pioglitazone are small
The base case results suggest that there is a 62% likelihood of
Vildagliptin being cost effective versus pioglitazone

Brennan A et al. Value Health 2008;11:A501 [Poster PDB19]

Cost comparison
charts

NHS Regional drug and therapeutics centre,

October 2009