Balancing the cost and benefits of modern biphasic insulin in primary care

Dr. Noor Lita Adam Consultant Endocrinologist Hospital tuanku Jaafar

The diabetes epidemic

North America

Significant increases in prevalence projected by 2030

Europe

37.7 51.2 36%

52.6 64.0 22%

Middle East and North Africa

Western Pacific

32.8 59.7 83%

Africa South and Central America

131.9 187.9 42%

Southeast Asia

14.7 28.0 90% World

71.4 120.9 69%

25.1 39.9 59%

2011 = 366 million 2030 = 552 million Increase 51%

Data shown for each region includes: Millions of people with diabetes 2011 Global projections for 2030 Projected increase from 2011 to 2030
Adapted from IDF Diabetes Atlas 5th Ed. 2011

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
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

Deaths attributable to diabetes as a percentage of all deaths (2079 years) by IDF region, 2011

16% 14% 12% 10% 8% 6% 4% 2% 0%

AFR EUR MENA SACA NAC SEA WP

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

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]
Rate of increase (%)

Ranking 1 2 3

Region North America and Caribbean Middle East South East Asia

People with diabetes (millions) 2010 37.4 26.6 58.7 2030 53.2 51.7 101.0

42.4% 93.9% 72.1%

1. IDF Diabetes Atlas 4th Edition 2009.

http://www.diabetesatlas.org

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

200,000

180,000
160,000 140,000

y = 130995e0.0208x R = 0.7959 y = 53166e0.0523x R = 0.8716

120,000
100,000 80,000

60,000
40,000 20,000

Circulatory diseases Projected, Circulatory diseases

Malignant neoplasms Projected, Cancer

Deaths in MOH Hospitals due to Circulatory Diseases & Cancer: Projections by 2020
20,000 18,000 16,000 14,000 12,000 10,000 8,000 6,000 4,000 y = 305.31x + 3776.1 R = 0.9542 y = 605.97x + 8657.9 R = 0.9027

2,000 0

Circulatory diseases Projected, Circulatory diseases

Malignant neoplasms Projected, Cancer

Primary Renal Diseases: Projections by 2020

New dialysis patients
9000 8000 7000

y = 314.5x + 1735.7 R = 0.9634

6000
5000 4000 3000 2000 1000 0

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.

2011

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2012

2013

2014

2015

2016

2017

2018

2019

2020

Intensive glucose control reduces mortality and morbidity

9

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 Any diabetes related end point Increased risk for every 1.0% higher HbA1c 21% 95% CI 17% - 24% p value p < 0.0001

Any myocardial infarction

Micro-vascular complications

14%
37%

8% - 21%
33% - 41%

p < 0.0001
p < 0.0001
[7]

Adapted from Stratton et al,

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

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]

10

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): 4348 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.

Morbidity is predominantly related to diabetes complications

11

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, 49:14891497. 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), 340349. 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 2079 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

4.1-fold increase

$7,987

2.4-fold increase

$4,749

$4,865
2.5-fold increase

$1,944

1.3-fold increase

$2,439

All insured patients

Diabetes, no complications

Diabetes, microvascular complications

Diabetes, macrovascular complications

Diabetes, microand macrovascular complications

Annual costs per patient

Based on an exchange rate of 1 Euro = 1.4156 US dollars. Exchange rate as of 30 Oct 2011 CODE-2 Study. Liebl et al. Diabetic Medicine 2001;126: 585-9

John and Peter have type 2 diabetes who will have the better life?
John
age 52 HbA1c 9,1%

Peter
age 52 HbA1c 7,0%

Peter will have the better life

Peter will live 20% longer than John Peter will live 60% longer without complications

Poor control

Good control

Peter will cost 20% Less than John

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

Earlier detection and better treatment reduces total healthcare costs

Lifetime costs in UK setting Percent

Anti diabetic medication (OAD and insulin) Implementation of anti diabetic medication

100

100 "John"
85

79
"Peter"

Management cost Complication costs

66

50
13 9 3 3 15 7

Better care reduces

cost by more than 20%

Baseline (HbA1c=9.1)

Earlier detection and better treatment (HbA1c=7.0)

Note:"Earlier detection & treatment" simulated as a patient population with no complications at diagnosis "better treatment" simulation of patients population treated to target of HbA 1c = 7.0 Source: CORE/IMS based on newly diagnosed UKPDS cohort at age 52

Changing diabetes barometer

COST RELATIVE TO 2010 BASE VALUES (%) 150 140 130 120 110 2019 100 90 ACHIEVING TARGETS

How can we reduce the costs associated with diabetes?

3 times investment cost

SOCIETY PROFIT

BREAK EVEN COST SAVINGS

INVESTMENT COST

2024

2010

2015

2020

2025

2030

Simulation using information from UKPDS and CORE diabetes model.

Changing diabetes barometer

COST RELATIVE TO 2010 BASE VALUES (%) 150 140 130 120 110 100 90
INVESTMENT COST

How can we reduce the costs associated with diabetes?

EARLY DETECTION
BREAK EVEN
4 times investment cost

SOCIETY PROFIT

COST SAVINGS

2015

2021

2010

2015

2020

2025

2030

Simulation using information from UKPDS and CORE diabetes model.

Changing diabetes barometer

COST RELATIVE TO 2010 BASE VALUES (%) 150 140
COST SAVINGS

How can we reduce the costs associated with diabetes?

PRIMARY PREVENTION
BREAK EVEN
12 times investment cost

SOCIETY PROFIT

130 120 110 100 90

INVESTMENT COST

2014

2018

2010

2015

2020

2025

2030

Simulation using information from UKPDS and CORE diabetes model.

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 around mealtimes could impact on adherence5

Adherence The possibility of hypoglycaemia and the lack of flexibility

Why are modern biphasic insulin superior to biphasic human insulin?

Functional benefits of Modern Insulins
Improved glycaemic control Improved adherence to treatment
Patients are less likely to develop diabetic complications that are expensive to treat

Better safety profile More dosing flexibility

References 1-10

Modern biphasic insulins provide better value than biphasic human insulin
Modern insulins improve glycaemic control and adherence/compliance to treatment, making patients less likely to develop diabetic complications that are expensive to treat

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 Nordisks 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
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

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

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 Patients find that their treatment regimen does not have to as great an impact on their lifestyle 9 plan mealtimes
Patients are more likely to comply with their treatment regimen and have better glycaemic control

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

Modern biphasic insulin are better than biphasic human insulin in controlling blood glucose levels with less hypoglycaemia
NovoMix 30 Better glycaemic control without an increase in hypoglycaemic events10

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)

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;94:35263

A1chieve regions and countries

Russia n=3074 China n=11,020 North Africa Algeria Libya Morocco Tunisia n=4039 South Asia Bangladesh India Pakistan n=22,447

Latin America Argentin a Mexico n=1138

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

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

66,726 people with type 2 diabetes

Home et al. Diabetes Res Clin Pract 2011;94:35263

A1chieve: participant distribution by pre-study therapy and allocated insulin

Pre-study therapy
(n=66726)

Study therapy
(n=66726)

Insulin OGLD 32.8%

No therapy 9.0%

Aspart 5.9%
Basal+aspart 6.2%

Others 3.2%

Detemir 23.3% OGLD alone 58.2% Biphasic aspart 30 61.4%

A1chieve subgroup: Change in HbA1c

Participants switching from BHI to BIAsp 30
Baseline HbA1c

9.4 465

0.0

p<0.001

-1.0 -1.5
Baseline to 24 weeks
Hussein Z et al. J Diab Invest 2012; 3 (Suppl. 1): 200 (Abstract PCS-18-1)

A1chieve subgroup: Change in FPG & PPG

Participants switching from BHI to BIAsp 30
FPG (mmol/L)
Baseline values n

PPG (mmol/L)

10.6
328

14.5
202

0.0 -1.50
-3.00 -4.50 -6.00
Baseline to 24 weeks
Hussein Z et al. J Diab Invest 2012; 3 (Suppl. 1): 200 (Abstract PCS-18-1)

p<0.001

Participants switching from BHI to BIAsp 30

Baseline 24 Weeks

Achievement of HbA1c targets <7%

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
p<0.001 p<0.001

Events/patient-year

p<0.001 P=0.00143

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

Participants switching from BHI to BIAsp 30

Pre-study Baseline
BIAsp 30 start dose

A1chieve subgroup: Insulin dose

End of study
BIAsp 30 end of study dose

Switchers from BHI

0.62 U/kg

Mean dose

0.65 U/kg
All doses are U/kg/day

0.71 U/kg

Significant lesser incidence of hypo with NovoMix 30 enables more patient to titrate their doses safely to reach the HbA1c target
El Ghazaly Harb et al. ADA-ME 2012

Participants switching from BHI to BIAsp 30

Patients on NPH pre-study Best imaginable health 100 90 80 70 60 50 40 30 20 10 0
80.0 73.4

Self-rated health (EQ-5D score)

Baseline

24 weeks

Worst imaginable health

Upgrade from BHI

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 long-term diabetes complications

Switching patients from BHI to NovoMix 30 is likely to reduce mortality and improve HRQoL

Switching patients from BHI to NovoMix 30 is likely to reduce the cost of complications

Switching patients from BHI to NovoMix 30 is cost-effective

37

Switching patients from BHI to 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]

NovoMix

38

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.

Switching patients from BHI to 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]

NovoMix

39

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.

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]

40

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.

Some studies have shown that switching patients from BHI to41 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

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 long-term diabetes complications

Switching patients from BHI to NovoMix 30 is likely to reduce mortality and improve HRQoL

Switching patients from BHI to NovoMix 30 is likely to reduce the cost of complications

Switching patients from BHI to NovoMix 30 is cost-effective

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]

43

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 PoorlyControlled Type 2 Diabetes Patients in China. Adv Ther 2008; 25(8): 752-774

Some studies have shown that switching patients from BHI to 44 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.

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]

45

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 metaanalysis. Clinical Therapeutics 2009; 31(8): 1641-1651.

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]

46

29. Reviriego J et al. Cost of severe hypoglycaemia in patients with type 1 diabetes in Spain and the costeffectiveness 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

Switching patients from BHI to NovoMix 30 is costeffective [25]

48

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

Switching patients from BHI to NovoMix 30 is costeffective [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]

49

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

Conclusions

Presentation title

Date

Slide no 50

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 nave people, and those already using insulin