LUNCH SYMPOSIUM Cost Benefirof NovoMix 30-Kuantan

Balancing the cost and benefits of modern biphasic insulin

in primary care

Dr. Noor Lita Adam

Consultant Endocrinologist

Hospital tuanku Ja’afar

The diabetes epidemic Significant increases in prevalence projected by 2030

Adapted from IDF Diabetes Atlas 5th Ed. 2011

North America Europe

Middle East and North Africa

Africa

South and Central America

Western Pacific

Southeast Asia

Data shown for each region includes: Millions of people with diabetes 2011 → Global projections for 2030

Projected increase from 2011 to 2030

World 2011 = 366 million

2030 = 552 million

Increase 51%

37.7 → 51.2 36%

25.1→39.9 59%

14.7→28.0 90%

32.8→59.7 83%

52.6→64.0 22%

71.4→120.9 69%

131.9→187.9 42%

Mortality associated with diabetes

• 4.6 million deaths due to diabetes in 2011

• 8.2% of all-cause mortality

• 48% in people aged <60 years

16%

Deaths attributable to diabetes as a percentage

of all deaths (20–79 years) by IDF region, 2011

14%

12%

10%

8%

6%

4%

0%

2%

AFR EUR MENA SACA NAC SEA WP

www.idf.org/diabetesatlas/5e/mortality (accessed April 2012)

AFR: Africa; EUR: Europe; IDF: International Diabetes Federation;

MENA: Middle East and North Africa; NAC: North America and

Caribbean; SACA: South and Central America; SEA: South-East Asia;

WP: Western Pacific

http://www.wdf.org/diabetesatlas/5e/mortality

4

The burden of diabetes

• The prevalence of diabetes is high and increasing rapidly

• The International Diabetes Federation (IDF) estimates that by 2030, 438

million people worldwide will have diabetes [1]

• It is estimated that up to one half of patients with diabetes will come from

North America and the Caribbean, the Middle East and South East Asia [1]

Ranking Region People with diabetes (millions) Rate of increase (%)

2010 2030

1 North America and

Caribbean 37.4

53.2 42.4%

2 Middle East 26.6 51.7 93.9%

3 South East Asia 58.7 101.0 72.1%

1. IDF Diabetes Atlas 4th Edition 2009. http://www.diabetesatlas.org

5

The burden of diabetes

• Diabetes is among the top ten leading causes of death

• Worldwide, almost 4 million deaths are attributable to diabetes (6.8% of all deaths) [1]

• This is a 5.5% increase over 2007 estimates and diabetes deaths will continue to increase unless urgent action is taken to address the problem[1]

• Diabetes decreases life expectancy by >7 years in patients aged >50 years [2]

• The CDC estimated that the risk of death among people with diabetes is twice that of people without diabetes of the same age [3]

1. IDF Diabetes Atlas 4th Edition 2009. http://www.diabetesatlas.org 2. Franco OH et al.. Associations of Diabetes Mellitus With Total Life Expectancy and Life Expectancy With and Without Cardiovascular Disease. Arch Intern Med. 2007;167(11):1145-1151. 3. CDC http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf

Admissions to MOH Hospitals due to Circulatory Diseases & Cancer:

Projections by 2020

y = 130995e0.0208x

R² = 0.7959

y = 53166e0.0523x

R² = 0.8716

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000

200,000

Circulatory diseases Malignant neoplasms

Projected, Circulatory diseases Projected, Cancer

Deaths in MOH Hospitals due to Circulatory Diseases & Cancer: Projections by 2020

y = 605.97x + 8657.9

R² = 0.9027

y = 305.31x + 3776.1

R² = 0.9542

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

20,000

Circulatory diseases Malignant neoplasms

Projected, Circulatory diseases Projected, Cancer

Primary Renal Diseases:

Projections by 2020

y = 314.5x + 1735.7 R² = 0.9634

0

1000

2000

3000

4000

5000

6000

7000

8000

90002001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

2019

2020

New dialysis patients

New dialysis patients Projected new dialysis patients

Diabetes mellitus

accounted for more

than half of the

primary renal

disease of new

dialysis patients

since 2003.

9

Intensive glucose control reduces mortality and

morbidity • Good control of blood glucose is the most important factor in the treatment

of diabetes: • A 1% drop in HbA1c is associated with a 21% decrease in mortality [7]

• The UKPDS and DCCT studies demonstrated that intensive glucose control significantly reduces diabetes complications

Complication Increased risk for every 1.0% higher HbA1c 95% CI p value

Any diabetes related end point 21% 17% - 24% p < 0.0001

Any myocardial infarction 14% 8% - 21% p < 0.0001

Micro-vascular complications 37% 33% - 41% p < 0.0001

Adapted from Stratton et al, [7]

7. Stratton IM et al.. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-412

10 Mortality is predominantly related to diabetes

complications • In developed countries, cardiovascular complications are the most

common cause of death in individuals with diabetes, causing more deaths than cancer, renal disorders and diabetes [2, 8-9]

2. Franco OH et al. Associations of Diabetes Mellitus With Total Life Expectancy and Life Expectancy With and Without Cardiovascular Disease. Arch Intern Med. 2007;167(11):1145-1151. 8. Roper NA et al. Cause-specific mortality in a population with diabetes. South Tees Diabetes Mortality Study. Diabetes Care 2002; 25 (1): 43–48 9. Morrish NJ et al.. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetoloia, 2001. 44 Suppl 2: p. S14-21.

11

Morbidity is predominantly related to diabetes

complications

• Diabetes related complications negatively impact on patient quality of life [11-13]

11. Wexler D et al.: Correlates of health-related quality of life in type 2 diabetes. Diabetologia 2006, 49:1489–1497. 12. Clarke P, Gray A, Holman R. Estimating utility values for health states of type 2 diabetic patients using the EQ-. 5D (UKPDS 62). Medical Decision Making, 22(4), 340–349. 13. Coffey JT et al.: Valuing health-related quality of life in diabetes. Diabetes Care 2002 , 25(12):2238-2243.

Diabetes is straining worldwide healthcare

budgets

• In 2011, the estimated global healthcare cost to

diagnose and treat diabetes was at least

$465 billion

• This comprised 11%* of total healthcare expenditure

in adults (aged 20–79 years)

*This calculation is based on the proportion of healthcare expenditure that people with diabetes consume because

of their diabetes condition, not their total heath annual expenditure

IDF. IDF Diabetes Atlas. 5th Edition. 2011. www.idf.org/diabetesatlas

Costs are dependent on complication status

$1,944 1.3-fold increase

$2,439




All insured patients

Diabetes, no complications

Diabetes, microvascular complications

Diabetes, macrovascular complications

Diabetes, micro- and macrovascular

complications

CODE-2 Study. Liebl et al. Diabetic Medicine 2001;126: 585-9

Annual costs per patient

Based on an exchange rate of 1 Euro = 1.4156 US dollars. Exchange rate as of 30 Oct 2011

John and Peter have type 2 diabetes – who will

have the better life?

John age 52

Peter age 52

Poor control Good control

HbA1c 9,1% HbA1c 7,0%

Peter will have the better life

Peter will live 20% longer

than John

Peter will live 60% longer without complications

Peter will cost 20% Less than John

Source: CORE/IMS based on newly diagnosed UKPDS cohort at age 52

Lifetime costs in UK setting Percent

100

79

85

9 3 3

66

13

15

7

0

50

100

Baseline (HbA1c=9.1)

Earlier detection and better treatment

(HbA1c=7.0)

"John"

"Peter"

Earlier detection and better treatment

reduces total healthcare costs Anti diabetic medication

(OAD and insulin)

Implementation of anti

diabetic medication

Management cost

Complication costs

Note:"Earlier detection & treatment" simulated as a patient population with no complications at diagnosis "better treatment" simulation of patients population treated to target of HbA1c = 7.0 Source: CORE/IMS based on newly diagnosed UKPDS cohort at age 52

Better care reduces

cost by more than 20%

CO

ST R

ELA

TIV

E TO

20

10

BA

SE V

ALU

ES (

%)

2010 2015 2020 2025 2030 90

100

110

120

130

140

150 ACHIEVING TARGETS

2019 2024

INVESTMENT COST

COST SAVINGS

BREAK EVEN

SOCIETY PROFIT 3 times investment cost

Simulation using information from UKPDS and CORE diabetes model.

Changing diabetes barometer How can we reduce the costs associated with diabetes?

CO

ST R

ELA

TIV

E TO

20

10

BA

SE V

ALU

ES (

%)

2010 2015 2020 2025 2030 90

100

110

120

130

140

150 EARLY DETECTION

2015 2021

INVESTMENT COST

COST SAVINGS

BREAK EVEN




CO

ST R

ELA

TIV

E TO

20

10

BA

SE V

ALU

ES (

%)

2010 2015 2020 2025 2030 90

100

110

120

130

140

150 PRIMARY PREVENTION

2014 2018

INVESTMENT COST

COST SAVINGS

BREAK EVEN




What are the limitations of older, traditional human

insulins?

• Hypoglycaemia – Relatively common side effect and the most feared complication of insulin therapy1

• Lack of flexibility – Having to inject at least 30 minutes prior to a meal, meaning meal times have to be planned2

• Weight gain – Consistent weight gain seen in both type 1 and type 2

diabetes3

• Variability/‘unpredictability’ – The same dose of insulin can have a different impact on glucose levels, making it harder to self-titrate treatment4

• Adherence – The possibility of hypoglycaemia and the lack of flexibility around mealtimes could impact on adherence5

Why are modern biphasic insulin superior to

biphasic human insulin?

Improved adherence to treatment

Patients are less likely to develop diabetic complications that are expensive to treat

Improved glycaemic control

Better safety profile

More dosing flexibility

Functional benefits

of Modern Insulins

References 1-10

Poor compliance to diabetes medication impairs blood glucose control, which results in expensive diabetic complications, such as blindness, amputations and kidney failure

Barriers to compliance with diabetes medication include patient fear of hypoglycaemia, weight gain and the inconvenience of planning mealtimes around treatment

Novo Nordisk’s portfolio of modern insulins are better at glycaemic control compared to human

insulin, and improve patient adherence as they reduce hypoglycaemic events, enable more flexible dosing and cause less weight gain

Modern insulins improve glycaemic control and adherence/compliance to treatment, making patients less likely to develop diabetic complications that are expensive to treat

Modern biphasic insulins provide better value than

biphasic human insulin

References 1-10

Modern biphasic insulin have a better safety profile than

biphasic human insulin

NovoMix® 30

Significantly

reduces the risk of

major

hypoglycaemic

events7

Patients have less fear of hypoglycaemia

Patients are more likely to comply with their treatment regimen and have better glycaemic control


Modern biphasic insulin allow for more dosing flexibility than biphasic human insulin

NovoMix® 30

Provides more

predictable control

and option of simple

intensification of

dosing / injections.

Faster acting -

removes necessity to

plan mealtimes9 Patients find that their treatment regimen does not have as great an impact on their lifestyle


Patients are more likely to comply with their treatment regimen and have better glycaemic control

NovoMix® 30

Better glycaemic control

without an increase in

hypoglycaemic events10

Modern biphasic insulin are better than biphasic human insulin in

controlling blood glucose levels with less hypoglycaemia

Patients’ blood glucose is better controlled throughout the day

HbA1c levels are reduced

Patients are less likely to develop diabetic complications that are

expensive to treat

Switch from biphasic human insulin

(BHI)

to BIAsp 30

Physicians Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy) PRESENT study

• Transferring type 2 diabetes patients with uncontrolled glycaemia from biphasic human insulin to biphasic insulin aspart 30

- to assess the safety and efficacy of biphasic insulin aspart (BIAsp30) used in routine clinical practice.

Shestakova, M. et al Current Medical Research and Opinion,

Volume 23, Number 12, Dec 2007 , pp. 3209-3214(6)

http://www.ingentaconnect.com/content/libra/cmro;jsessionid=3r1seqg9dgc7s.alexandra

PRESENT study - results

Glycaemia improved significantly (mean ± SD):

• HbA1c by 1.58 ± 1.69% points (from 9.32 ± 1.64% to 7.70 ± 1.29%),

• FPG by 2.92 ± 3.71 mmol/L and PPPG by 4.75 ± 4.87 mmol/L.

• The incidence of hypoglycaemic episodes decreased over time, from 38.7% (baseline) to 20.8% (6 months).

In this observational study, in the type 2 diabetes mellitus patients who were poorly controlled on BHI, glycaemia improved when transferred to BIAsp30, and a lower incidence or rate of hypoglycaemia was observed in these patients.

A1chieve® global data

Home et al. Diabetes Res Clin Pract 2011;94:352–63

A1chieve® regions and countries

Home et al. Diabetes Res Clin Pract 2011;94:352–63

Latin America Argentina Mexico n=1138

South Asia Bangladesh India Pakistan n=22,447

North Africa Algeria Libya Morocco Tunisia n=4039

Middle East Bahrain Egypt Iran Jordan Kuwait Oman Qatar Saudi Arabia Turkey UAE n=14,976

China n=11,020

Russia n=3074

East Asia Korea Malaysia Philippines Singapore Taiwan n=10,032

66,726 people with type 2 diabetes

Detemir 23.3%

Insulin ± OGLD 32.8%

No therapy 9.0%

OGLD alone

58.2%

Basal+aspart 6.2%

Others 3.2%

Aspart 5.9%

A1chieve: participant distribution by pre-study

therapy and allocated insulin

Study therapy (n=66726)

Pre-study therapy (n=66726)

Biphasic aspart 30 61.4%

A1chieve subgroup: Change in HbA1c Participants switching from BHI to BIAsp 30

Hussein Z et al. J Diab Invest 2012; 3 (Suppl. 1): 200 (Abstract PCS-18-1)

Baseline to 24 weeks

Baseline HbA1c 9.4 n 465

p<0.001

-1.0

-1.5

0.0

A1chieve subgroup: Change in FPG & PPG Participants switching from BHI to BIAsp 30

FPG (mmol/L) PPG (mmol/L)

Baseline values 10.6 14.5

n 328 202

-1.50

-4.50

-3.00

0.0

-6.00

Baseline to 24 weeks

p<0.001


Achievement of HbA1c targets <7% Participants switching from BHI to BIAsp 30

Baseline 24 Weeks

12 78

8x more patients achieved

target on BIAsp 30 after

upgrading from BHI

Hussein et al. IDF-WPR NovoMix8 2012

A1chieve subgroup: Rate of overall hypos Participants switching from BHI to BIAsp 30

Ev

en

ts/p

atie

nt-

ye

ar


P=0.00143

p<0.001

p<0.001

p<0.001

A1chieve subgroup: Insulin dose Participants switching from BHI to BIAsp 30

BIAsp 30 start dose

0.65 U/kg

BIAsp 30 end of study dose

0.71 U/kg

Baseline End of study

El Ghazaly Harb et al. ADA-ME 2012 Hussein et al. IDF-WPR NovoMix8 2012

Pre-study

Mean dose

0.62 U/kg Switchers

from BHI

All doses are U/kg/day

Significant lesser incidence of hypo with NovoMix

30 enables more patient to titrate their doses safely

to reach the HbA1c target

Self-rated health (EQ-5D score) Participants switching from BHI to BIAsp 30

0

10

20

30

40

50

60

70

80

90

100

Patients on NPH pre-study

Baseline 24 weeks

Best imaginable health

Worst imaginable health

73.4

80.0

APROM ID#1932;approval date:July 2010 37

Upgrade from BHI

Switching patients from BHI to NovoMix® 30 is likely to reduce long-term diabetes complications

Switching patients from BHI to NovoMix® 30 is cost-effective

Switching patients from BHI to NovoMix® 30 is likely

to reduce mortality and improve HRQoL

Diabetes places a substantial epidemiological and economic burden on global healthcare systems

Mortality, morbidity and costs associated with diabetes are mainly related to diabetes complications


to reduce the cost of complications

38

Switching patients from BHI to NovoMix® 30 reduces long-term complications [14]

• A study conducted in China showed significant projected reductions in diabetes complications when patients were switched to NovoMix® 30 [14]

ESRD: End-stage renal disease; PVD: Peripheral vascular disease; MI: Myocardial infarction; CHF: Congenital heart failure; PDR: Peripheral diabetic retinopathy.

14. Lynch M et al. Cost-effectiveness of biphasic insulin aspart 30 versus biphasic human insulin for type 2 diabetes patients in China. Poster presented at 10th Annual ISPOR European Congress, 23-27th October 2007, Dublin, Ireland.

39

Switching patients from BHI to NovoMix® 30 reduces long-term complications [15]

• A study conducted in Poland showed significant projected reductions in diabetes complications when patients were switched to NovoMix® 30 [15]

ESRD: End-stage renal disease; PVD: Peripheral vascular disease; AMI: Acute Myocardial infarction; CHF: Congenital heart failure; PDR: Peripheral diabetic retinopathy.

15. Aristides M et al. Cost-effectiveness of biphasic insulin aspart 30 versus biphasic human insulin for type 2 diabetes in a Polish setting. Poster presented at 10th Annual ISPOR European Congress, 23-27th October 2007, Dublin, Ireland.

40

NovoMix® 30 improves treatment satisfaction[16]

• Overall treatment satisfaction, measured by the DiabMedSat, was significantly improved after treatment with NovoMix® 30 in the IMPROVE study [16]

• Improvements were considered large enough to be clinically meaningful to patients with type 2 diabetes [16]

16. Brod M et al. Patient Treatment Satisfaction after Switching to NovoMix® 30 (BIAsp 30) in the IMPROVE™ Study – An analysis of the influence of prior and current treatment factors. In Press Quality of Life Research.

41

Some studies have shown that switching patients from BHI to

NovoMix® 30 reduces mortality and improves HRQoL [21]

• Switching patients to NovoMix® 30 is expected to increase life expectancy and quality-adjusted life expectancy [21]

21. Valentine WJ et al. Systematic review of the cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes. Curr Med Res Opin 2010.

42

Upgrade from BHI

Switching patients from BHI to NovoMix® 30 is likely to reduce long-term diabetes complications

Switching patients from BHI to NovoMix® 30 is cost-effective


to reduce mortality and improve HRQoL

Diabetes places a substantial epidemiological and economic burden on global healthcare systems

Mortality, morbidity and costs associated with diabetes are mainly related to diabetes complications

Switching patients from BHI to NovoMix® 30 is likely to

reduce the cost of complications

43

Some studies have shown that switching patients from BHI to

NovoMix® 30 reduces the cost of diabetes complications [22]

• A study conducted in China showed that NovoMix® 30 is likely to reduce long-term diabetes complication costs [22]

The use of NovoMix® 30 results in a 14% reduction in the cost of diabetes complications

(from CNY 120,980 to CNY 103,726)

22. Palmer J et al. Cost-Effectiveness of Switching to Biphasic Insulin Aspart in Poorly- Controlled Type 2 Diabetes Patients in China. Adv Ther 2008; 25(8): 752-774

44 Some studies have shown that switching patients from BHI to

NovoMix® 30 reduces the cost of diabetes complications [15]

• A study conducted in Poland showed that NovoMix® 30 is likely to reduce long-term diabetes complication costs [15]

Switching patients to NovoMix® 30 is projected to reduce the cost of diabetes complications by >40% (from PLN 27,183

to PLN 15,913)

Pharmacy costs include insulin usage plus delivery devices, OAD usage and blood glucose monitoring; Management costs include foot and eye screening programs and concomitant medications (aspirin, ACE inhibitors or ARBs and statins); Complication costs incurred in the treatment of cardiovascular, renal and eye disease, foot ulcers and amputation, neuropathy and hypoglycaemia are also accounted for.

15. Aristides M et al. Cost-effectiveness of biphasic insulin aspart 30 versus biphasic human insulin for type 2 diabetes in a Polish setting. Poster presented at 10th Annual ISPOR European Congress, 23-27th October 2007, Dublin, Ireland.

45

Patients treated with NovoMix® 30 experience fewer major

hypoglycaemic events [28]

• A recent meta-analysis demonstrates a 45% reduction in the rate of major

hypoglycaemic events with NovoMix® 30 compared with BHI (P<0.01) [28]

28. Davidson JA et al. Risk for nocturnal hypoglycemia with biphasic insulin aspart 30 compared with biphasic human insulin 30 in adults with type 2 diabetes mellitus: a meta-analysis. Clinical Therapeutics 2009; 31(8): 1641-1651.

46

Hypoglycaemic events represent a significant cost burden to the society

• Major hypoglycaemias…

• are associated with a significant increase in medical expenditures such as emergency room visits and inpatient costs [29]

• could represent around 27% of the total annual total cost of diabetes [29]

29. Reviriego J et al. Cost of severe hypoglycaemia in patients with type 1 diabetes in Spain and the cost-effectiveness of insulin lispro compared with regular human insulin in preventing severe hypoglycaemia. Int J Clin Pract 2008; 62(7):1026-32.

47

Switching patients from BHI to NovoMix® 30

is cost-effective in many countries

48 Switching patients from BHI to NovoMix® 30 is cost-

effective [25]

• In the US, NovoMix® 30 is cost-effective relative to BHI with a cost/QALY of $29,870 [25]

• At a willingness to pay of $50,000/QALY gained, there is 94.8% chance that switching patients from BHI to NovoMix® 30 is cost-effective [25]

25. Aagren M et al. Projected cost-effectiveness of biphasic insulin aspart 30 in type 2 diabetes patients switched from biphasic human insulin in the United. Poster presented at 14th Annual ISPOR International Meeting, 16th-20th May 2009, Orlando, FL, USA

49

Switching patients from BHI to NovoMix® 30 is cost-

effective [22] • In China, NovoMix® 30 is cost-effective relative to BHI with a cost/QALY of CNY 1,926 [22]

• At a willingness to pay of CNY 100,000 /QALY gained, there is 100% chance that switching patients from BHI to NovoMix® 30 is cost-effective [22]

22. Palmer J et al. Cost-Effectiveness of Switching to Biphasic Insulin Aspart in Poorly-Controlled Type 2 Diabetes Patients in China. Adv Ther 2008; 25(8): 752-774

Conclusions

• As the prevalence of type 2 DM increases world wide the cost to manage the metabolic abnormalities and diabetic complications are also increased

• The total cost in managing these diabetic patients is not only in the treatment itself but as a whole including the management of complications

• In people in poor blood glucose control, starting a premix insulin analogue :

•Blood glucose control measured as HbA1c, FPG or PPPG improved markedly – clinically & statistically significantly

•This was not accompanied by an increase in reported hypoglycaemia, or in body weight

•Useful improvements in blood glucose control were seen both in insulin naïve people, and those already using insulin

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LUNCH SYMPOSIUM Cost Benefirof NovoMix 30-Kuantan

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