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Type 2 Diabetes: Disease State Overview. AF2086R0. Suggestions for Slide Deck Use. The following unbranded slides are provided as a disease state library and may be used as background information at the beginning of any promotional program - PowerPoint PPT Presentation

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Page 1: Type 2 Diabetes:  Disease State Overview

Type 2 Diabetes: Disease State Overview

AF2086R0

Page 2: Type 2 Diabetes:  Disease State Overview

Suggestions for Slide Deck Use

• The following unbranded slides are provided as a disease state library and may be used as background information at the beginning of any promotional program

• These slides should always supplement the affirmative deck unless the program is scheduled to be "disease state only"

Page 3: Type 2 Diabetes:  Disease State Overview

Diabetes Disease State Overview

• Diabetes: epidemiology/pathophysiology – Prevalence and burden of diabetes

– Core defects of type 2 diabetes

– Complications and costs associated with type 2 diabetes

– Predicting and preventing type 2 diabetes

• Treatment goals and strategies – Improving glycemic control

– Reducing diabetes-related complications

– Treating the whole patient

Page 4: Type 2 Diabetes:  Disease State Overview

Every Day in the United States Approximately…

*Patients ages ≥20 years.Centers for Disease Control. National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf. Accessed March 5, 2009.

66 people lose their eyesight

because of diabetes

66 people lose their eyesight

because of diabetes

128 people begintreatment for end-stagerenal disease (ESRD)

128 people begintreatment for end-stagerenal disease (ESRD)

640 people die fromdiabetes and itscomplications

640 people die fromdiabetes and itscomplications

195 lower-limbamputations are performed

because of diabetes

195 lower-limbamputations are performed

because of diabetes

More than 4000 newcases* of diabetes will be

diagnosed today

More than 4000 newcases* of diabetes will be

diagnosed today

Page 5: Type 2 Diabetes:  Disease State Overview

≈23.5 Million (10.7%) Americans 20 Years or Older Have Diabetes (Diagnosed or Undiagnosed)*

*Data is from 2003–2006, projected to year 2007.NIDDK. National Diabetes Statistics. 2007. Available at: http://diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people.Accessed February 11, 2009.

0

5

10

15

20

25

Age group

2.6

10.8

23.8

20–39 40–59 60+

Perc

enta

ge

Page 6: Type 2 Diabetes:  Disease State Overview

*Data is from 2004–2006, projected to year 2007.NIDDK. National Diabetes Statistics. November 2007. Available at: http://diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people.Accessed February 11, 2009.

0

200,000

400,000

600,000

800,000

1,000,000

Age group20–39 40–59 60+

Num

ber

Adults Diagnosed with Diabetes in the United States*

1.6 million new cases of diabetes were diagnosed in people aged 20 years or older in 2007

Total economic costs of diabetes estimated to be

$174 billion (2007)

281,000

819,000

536,000

Page 7: Type 2 Diabetes:  Disease State Overview

Age-adjusted Total Prevalence of Diabetes in the United States by Race/Ethnicity (Age ≥20)

0 2 4 6 8 10 12 14 16 18 20

Non-Hispanic Whites

Hispanic/Latino Americans

Non-Hispanic Blacks

American Indians/Alaska Natives

Percentage

17

12

10

7

NIDDK. National Diabetes Statistics. November 2007. Available at: http://diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people.Accessed February 11, 2009.

Asian Americans 8

Page 8: Type 2 Diabetes:  Disease State Overview

Economic Consequences of Diabetes

Total Annual Cost in 2002: $132 Billion

Disability and early mortality

$40 billion

Diabetes and diabetes supplies$23 billion

Chronic complications$25 billion

$44 billion

General medical conditions

Indirect costs* = $40 billion Direct costs† = $92 billion

Stolar MW et al. JMCP. 2008;14:S1–S19.

*Indirect costs include lost productivity, disability, and premature mortality.†Direct costs include: hospital inpatient care, nursing home care, physician office visits, total home healthcare costs, costs associated with hospice care, and diabetes supplies.

Page 9: Type 2 Diabetes:  Disease State Overview

0

1000

2000

3000

4000

5000

6000

7000

0 5 10 15

Annual Medical Expenditures and Length ofTime with Diabetes

Duration of Diabetes (Years)

Cos

t in

2005

(dol

lars

)

Diagnosis of diabetes at age 50

Diagnosis of diabetes at age 65

Adapted from Trogdon JG et al. Diabetes Care. 2008;31:2307–2311.

Annual cost increases with length of time with diabetes

Page 10: Type 2 Diabetes:  Disease State Overview

Pathophysiology of Type 2 Diabetes

• Type 2 diabetes results from a progressive insulin secretory defect on the background of insulin resistance1

• Key pathophysiologic mechanisms leading to hyperglycemia in type 2 diabetes

– Insulin resistance2,3

– Beta-cell dysfunction3

1. American Diabetes Association. Diabetes Care. 2009;32:S13–S61. 2. DeFronzo RA. Med Clin North Am. 2004;88:787–835.3. Kahn SE. J Clin Endocrinol Metab. 2001;86:4047–4058.

Page 11: Type 2 Diabetes:  Disease State Overview

Two Defects Contributing to Type 2 Diabetes

1. Buchanan TA. Clin Ther. 2003;25(suppl 2):B32–B46.2. Kahn SE. J Clin Endocrinol Metab. 2001;86:4047–4058.

Type 2 DiabetesType 2 Diabetes

Beta-cellBeta-cell

InsulinInsulinresistanceresistance

InsulinInsulinresistanceresistance

Beta-cell Beta-cell dysfunctiondysfunction

Beta-cell Beta-cell dysfunctiondysfunction

Muscle tissueMuscle tissue

Adipose tissueAdipose tissue

Obesity (visceral)1Obesity (visceral)1

PancreasPancreas

Obesity (visceral)2Obesity (visceral)2

LiverLiver

Page 12: Type 2 Diabetes:  Disease State Overview

Natural Progression of Insulin Resistance in Patients with Type 2 Diabetes1,2

Normal glycemia

Insulin resistance rises, leading to

beta cells working overtime to secrete

more insulin

Beta cells are unable to produce the insulin needed to compensate for the increased

level of insulin resistance, causing glucose levels to rise, leading to type 2 diabetes*

*Type 2 diabetes is diagnosed when FPG is ≥126 mg/dL.3

Adapted from International Diabetes Center, Minneapolis, MN.1

Insulin resistanceInsulin production & secretion/ Beta-cell functionFasting plasma glucose

1. Bergenstal RM et al. Endocrinology. 4th ed. Philadelphia, PA: WB Saunders Company;2001:821–835. 2. Ramlo-Halsted BA, Edelman SV. Clin Diab. 2000;18:80–85. 3. American Diabetes Association. Diabetes Care. 2008;31(suppl1):S12–S54.

Page 13: Type 2 Diabetes:  Disease State Overview

DiabeticRetinopathy

Leading causeof blindnessin adults

DiabeticNephropathy

Major cause of kidney failure

CardiovascularDisease

Stroke

DiabeticNeuropathy

Major cause of lower extremity amputations

CV Disease & Stroke account for ~65% of deaths in T2D patients

Type 2 Diabetes Associated with Serious Complications

CV = cardiovascular.National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States, 2005. Bethesda, MD: U.S. Department of Health and Human Services, National Institute of Health, 2005.

Page 14: Type 2 Diabetes:  Disease State Overview

Prevalence of Multiple Complications Among People with Type 2 Diabetes

No complications42.1%

2 complications10.3%

3 complications6.7%

4 or more complications

7.6%

1 complication33.3%

American Association of Clinical Endocrinologists. State of Diabetes Complications in America Report. Available at: http://www.aace.com/newsroom/press/2007/images/DiabetesComplicationsReport_FINAL.pdf. Accessed March 5, 2009.

Page 15: Type 2 Diabetes:  Disease State Overview

*In NHANES, “chronic kidney disease" refers to people with microalbuminuria (albumin:creatinine ratio >30 µg/mg).†In the NHANES analysis, "foot problems" includes foot/toe amputations, foot lesions, and numbness in the feet.‡"Eye damage" includes a positive response by NHANES participants to the question, "Have you been told diabetes has affected your eyes/had retinopathy?" Retinopathy is damage to the eye's retina. In NHANES, people without diagnosed diabetes were not asked this question, therefore, prevalence information for nondiabetics is not available.CHD = coronary heart disease; CHF = congestive heart failure.

9.8 9.5 9.17.9

6.6

27.8

22.9

18.9

1.8 1.7 2.1 1.1 1.8

6.1

10

0

10

20

30

Heart attack Chest pain CHD CHF Stroke Chronic kidneydisease

Foot problems Eye damage

Perc

enta

ge w

ith c

ompl

icat

ions

Diagnosed diabetes

Normal blood sugar levels

Prevalence of Macrovascular and Microvascular Complications of Diabetes

Macrovascular Microvascular

American Association of Clinical Endocrinologists. State of Diabetes Complications in America Report. Available at: http://www.aace.com/newsroom/press/2007/images/DiabetesComplicationsReport_FINAL.pdf. Accessed March 9, 2009.

*† ‡

Page 16: Type 2 Diabetes:  Disease State Overview

Prevalence of Diabetic Retinopathy

*95% CI: 38.8%–41.7%†95% CI: 7.4%–9.1%‡Diabetic retinopathy defined as a retinal vascular disorder characterized by signs of retinal ischemia and/or signs of increased retinal vascular permeability. Retinopathy severity level ≥14 retinopathy and/or macular edema.§Vision threatening retinopathy defined as severe retinopathy and/or diabetic macular edema. Retinopathy severity level ≥50 and/or macular edema.Kempen JH et al. Arch Ophthalmol. 2004;122:552–563.

0

10

20

30

40

50

Diabetic retinopathy Vision-threateningretinopathy

8.2%†

40.3%*

§

Prev

alen

ce o

f ret

inop

athy

in

dia

betic

s ag

e ≥4

0 ye

ars

(%)

Page 17: Type 2 Diabetes:  Disease State Overview

Number of Cases with ESRD Due to Diabetic Nephropathy Is Increasing in the United States

1991 19921990 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 0

10

20

30

40

50

Num

ber o

f cas

es

(thou

sand

s)

Year

Diabetes is the leading cause of ESRD

ESRD = end-stage renal disease.CDC. Morbidity and Mortality Weekly Report. 2005;54(43)1097–1100.

Page 18: Type 2 Diabetes:  Disease State Overview

CV Risk in Patients with Diabetes and No Prior MI Is Similar to Risk in Nondiabetics with Prior MI

Schramm TK et al. Circulation. 2008; 117:1945–1954.

5-ye

ar in

cide

nce

(%)

CV = cardiovascular. For CV death, the hazard ratio was 2.42 in men with diabetes only and 2.44 in men with a prior MI only ( P=0.60). Results for women were 2.45 and 2.62, respectively (P<0.001).

20.124.5

3.5 3.7

34.1

39.8

14.6 15.6

05

1015202530354045

CV death CV death

No diabetes/prior MINo diabetes/no prior MIDiabetes/prior MIDiabetes/no prior MIMen Women

A population study of 3.3 million people

Page 19: Type 2 Diabetes:  Disease State Overview

Annual National Cost of Type 2 Diabetes and Related Complications*

$22.9

$57.1

$1.8

$8.4

$0.0

$10.0

$20.0

$30.0

$40.0

$50.0

$60.0

$70.0

Complications alone Diabetes and complications

National total expenditures

National out-of-pocket costs

*Cost estimates in this report were adjusted for inflation to reflect 2006 costs.American Association of Clinical Endocrinologists. State of Diabetes Complications in America Report. Available at: http://www.aace.com/newsroom/press/2007/images/DiabetesComplicationsReport_FINAL.pdf. Accessed March 5, 2009.

Cos

t in

billi

ons

Page 20: Type 2 Diabetes:  Disease State Overview

Individual Costs by Complication*

Annual Healthcare Costs

*Cost estimates in this report were adjusted for inflation to reflect 2006 costs.American Association of Clinical Endocrinologists. State of Diabetes Complications in America Report. Available at: http://www.aace.com/newsroom/press/2007/images/DiabetesComplicationsReport_FINAL.pdf. Accessed March 5, 2009.

$ 1785

$ 4687

$ 6062

$ 7806

$ 7932

$ 9002

$ 14,150

$ $ $ $ $ $ $ $ $

$ 153

$ 480

$ 224

$ 448

$ 510

$ 439

$ 574

0 2000 4000 6000 8000 10,000 12,000 14,000 16,000

Heart attack

Chronic kidney disease

CHF

Stroke

CHD

Foot problems

Eye damage Total expenditures

Out-of-pocket costs

Page 21: Type 2 Diabetes:  Disease State Overview

Algorithm to Estimate Type 2 Diabetes Risk

Item Points

Fasting glucose level 100–126 mg/dL, yes/no 10

Body mass index (BMI) 25.0–29.9, yes/no 2

BMI ≥30.0, yes/no 5

High-density lipoprotein cholesterol (HDL-C) level <40 mg/dL in men or <50 mg/dL in women, yes/no

5

Parental history of diabetes mellitus, yes/no 3

Triglyceride level ≥150 mg/dL, yes/no 3

Blood pressure ≥130/85 mmHg or receiving treatment, yes/no 2

According to a study in a middle-aged white population, total points ≥25 corresponds to >35% 8-year risk of type 2 diabetes.

Wilson PW et al. Arch Intern Med. 2007;167:1068–1074.

Page 22: Type 2 Diabetes:  Disease State Overview

Preventing Development of Type 2 Diabetes

• Screening for prediabetes and asymptomatic type 2 diabetes should be considered in adults who are overweight or obese (BMI ≥25 kg/m2) and have additional risk factors

• In those without risk factors, testing should begin at age 45 years

• If results are normal, testing should be repeated at least every 3 years

• Counseling on lifestyle modification is recommended for patients with impaired fasting glucose or impaired glucose tolerance

– Weight-loss goal of 5%–10% of initial body weight

– Physical activity with moderate intensity for 150 minutes per week

American Diabetes Association. Diabetes Care. 2009;32(suppl 1):S13–S61. American Diabetes Association. Diabetes Care. 2009;32(suppl 1):S13–S61.

Page 23: Type 2 Diabetes:  Disease State Overview

Summary of Diabetes: Epidemiology/Pathophysiology

• Diabetes and diabetes-related complications (eg, heart disease, kidney disease, blindness, amputations) are highly prevalent1

• The pathophysiology of diabetes involves the development of insulin resistance and beta-cell dysfunction2

• Diabetes is strongly correlated with a number of microvascular risk factors and diseases, and is a contributor to macrovascular disease and mortality1

• Routine clinical measures may be used to identify patients at risk of developing type 2 diabetes who may benefit from lifestyle counseling3

1. NIDDK. National Diabetes Statistics. November 2007. Available at: http://diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people.Accessed February 11, 2009.2. Kahn SE. J Clin Endocrinol Metab. 2001;86:4047–4058.3. American Diabetes Association. Diabetes Care. 2009;32(suppl 1):S13–S61.

Page 24: Type 2 Diabetes:  Disease State Overview

Diabetes Disease State Overview

• Diabetes: epidemiology/pathophysiology – Prevalence and burden of diabetes

– Core defects of type 2 diabetes

– Complications and cost associated with type 2 diabetes

– Predicting and preventing type 2 diabetes

• Treatment goals and strategies – Improving glycemic control

– Reducing diabetes-related complications

– Treating the whole patient

Page 25: Type 2 Diabetes:  Disease State Overview

Criteria for the Diagnosis of Diabetes Mellitus: ADA Standards of Medical Care, 2009

• FPG 126 mg/dL (7.0 mmol/L)– Fasting is defined as no caloric intake for at least 8 hours

OR• Symptoms of hyperglycemia plus casual plasma glucose concentration

200 mg/dL (11.1 mmol/L)– Casual is defined as any time of day without regard to time since last meal– The classic symptoms of hyperglycemia include polyuria, polydipsia, and

unexplained weight loss

OR• 2-h plasma glucose 200 mg/dL (11.1 mmol/L) during an OGTT

– The test should be performed as described by WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water

ADA = American Diabetes Association; OGTT = oral glucose tolerance test, WHO = World Health Organization.American Diabetes Association. Diabetes Care. 2009;32:S13–S61.

ADA = American Diabetes Association; OGTT = oral glucose tolerance test, WHO = World Health Organization.American Diabetes Association. Diabetes Care. 2009;32:S13–S61.

Page 26: Type 2 Diabetes:  Disease State Overview

Recommendations for Early Pharmacologic Treatment from AACE and ADA

• To reduce the risk of serious disease-related complications,1,2 AACE recommends

– Target A1C goal of ≤6.5%2

– Earlier intervention with appropriate therapies and persistent titration to achieve goal2

• ADA recommends3

– Target A1C goal of <7% “for most patients”

– Achieving and maintaining glycemic goals and changing interventions when therapeutic goals are not being met

AACE = American Association of Clinical Endocrinologists.1. Stratton IM et al. BMJ. 2000;321:405–412.2. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13(suppl 1):4–68.3. American Diabetes Association. Diabetes Care. 2009;32:S13–S61.

Page 27: Type 2 Diabetes:  Disease State Overview

United Kingdom Prospective Diabetes Study (UKPDS)

Conventional MonotherapiesUnable to Maintain Glycemic Control Over Time

Med

ian

A1C

(%)

Time from randomization (years)

Glibenclamide (glyburide)

Conventional*

Insulin

MET

0

6

7

8

10

0 3 6

9

9 12 15

ADA Goal

AACE Goal

FPG = fasting plasma glucose; MET = metformin.*Conventional therapy defined as dietary advice given at 3-month intervals where FPG was targeted at best levels feasible in clinical practice. If FPG exceeded 270 mg/dL, patients were re-randomized to receive nonintensive MET, chlorpropamide, glibenclamide, or insulin. If FPG exceeded 270 mg/dL again, those on SU would have MET added. If FPG exceeded 270 mg/dL after this, insulin was substituted.

Adapted from UK Prospective Diabetes Study (UKPDS 34) Group. Lancet. 1998;352:854–865.

Page 28: Type 2 Diabetes:  Disease State Overview

Patients reaching glycemic target

Glycemic Targets Are Not Being Achieved Worldwide

DICE = Diabetes in Canada Evaluation; NHANES = National Health and Nutrition Examination Surveys; RECAP-DM = Real-life Effectiveness and Care Patterns of Diabetes Management.1. Harris SB et al. Diabetes Res Clin Pract. 2005;70:90–97. 2. Ong et al. Ann Epidemol. 2008;18:222–229. 3. Guisasola et al. Diabetes Obes Metab. 2008;10:8–15.

UNITED STATES (NHANES)2

HbA1c <7%

57%

43%

EUROPE(RECAP-DM)3

HbA1c <6.5%

74%

CANADA(DICE)1

HbA1c <7%

51%

49% 26%

Patients not reaching glycemic target

Page 29: Type 2 Diabetes:  Disease State Overview

Length of time between first monotherapy(A1C >8.0%) and switch/addition in therapy*

*May include uptitration. Based on a prospective, population-based study using retrospective observational data.Brown JB et al. Diabetes Care. 2004;27:1535–1540.

Months

26.5

35.1

0 6 12 18 24 30 36

MET Only

SU Only

Patients Remain on Monotherapy >2 Years After First A1C >8.0%*

Page 30: Type 2 Diabetes:  Disease State Overview

Risk of CV Events or Death Increased with HbA1c Level (EPIC-Norfolk)

Age

-adj

uste

d re

lativ

e ris

k (9

5% C

I)

Khaw KT et al. Ann Intern Med 2004; 141:413–420.

Men

0

1

2

3

4

5

6

7

8

CHD events CVD events All-causemortality

CHD events CVD events All-causemortality

Women

5–5.4% 5.5–5.9% 7%6.5–6.9%6.0–6.4%HbA1c level:

P0.001 for linear trend across HbA1c categories for all endpoints.CHD = coronary heart disease; CI = confidence interval; CVD = cardiovascular disease; EPIC-Norfolk = European prospective investigation into cancer in Norfolk.

1.56

2.002.13

3.44

7.07

1.231.56

1.79

3.03

5.01

1.251.57

1.80

3.49 3.38

0.96 1.04

2.29

3.06

4.73

0.890.98

1.63

2.37

7.96

1.021.28

1.61 1.70

6.91

Page 31: Type 2 Diabetes:  Disease State Overview

Multifactorial Approach: Strategies for Reducing Diabetic Complications—Treating the Whole Patient

• Strategies for reducing microvascular complications

– Routine screening for diabetes

– Optimized glycemic control

– Optimized BP control

• Strategies for reducing macrovascular complications

– Optimized glycemic control

– Treatment of hypertension and other established cardiovascular risk factors in diabetic and possibly prediabetic subjects*

– Lipid control*

– Antiplatelet therapy*

*For appropriate patient population based on treatment guidelines.American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12–S54.

*For appropriate patient population based on treatment guidelines.American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12–S54.

Page 32: Type 2 Diabetes:  Disease State Overview

Stratton IM et al. BMJ. 2000;321:405–412.

Improved Glycemic Control Has Been Shown to Help Reduce the Risk of Complications

According to the United Kingdom Prospective DiabetesStudy (UKPDS) 35, every 1% decrease in A1C resulted in:

Decrease in risk of any

diabetes-related endpoint

(P<0.0001)

21%

Decrease in risk of

microvascularcomplications

(P<0.0001)

37%

Page 33: Type 2 Diabetes:  Disease State Overview

UKPDS: Long-Term Intensive Glucose Control in Type 2 Diabetes

• Multicenter, randomized study with 10-year follow-up1

– One of the longest and largest type 2 diabetes trials ever conducted2

– 4209 patients newly diagnosed with type 2 diabetes1

• Study Design– After a 3-month run-in period, patients with FPG >108 mg/dL but <270 mg/dL

were randomized to receive either intensive therapy (SU or insulin or, if more than 120% of ideal body weight, MET) or conventional therapy (diet only)1

• Primary study objective– To determine whether long-term improved glycemic control was able to sustain

risk reductions in microvascular complications, and if intensive therapy had a long-term effect on macrovascular outcomes1

• Primary outcome– Prespecified aggregate clinical outcomes were any diabetes-related endpoint,

diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease1

FPG = fasting plasma glucose.1. Holman et al. N Engl J Med. 2008;359:1577–1589.2. Lawton J et al. Br J Gen Pract. 2003;53:394–398.

Page 34: Type 2 Diabetes:  Disease State Overview

Sustained Intensive Glycemic Control Can Reduce Diabetes-Related Complications

• Long-term intensive glycemic control is associated with a significantly decreased risk of MI or death from any cause, in addition to known risk reductions in microvascular disease

Any diabetes-relatedendpoint

(P = 0.04 for SU-insulin;P = 0.01 for MET)

Microvasculardisease

(P = 0.001 for SU-insulin;P = 0.31 for MET)

Myocardialinfarction

(P = 0.01 for SU-insulin;P = 0.005 for MET)

Death fromany cause

(P = 0.007 for SU-insulin;P = 0.002 for MET)

SU-insulin

METSU-

insulinMET

SU-insulin

METSU-

insulinMET

-21%-24%

-15%-13%

-16%

-33%

-27%

-9%

Holman et al. N Engl J Med. 2008;359:1577–1589.

Risk Reductions for Intensive-Therapy Regimens at 10-Year Follow-up

Page 35: Type 2 Diabetes:  Disease State Overview

Treating the Whole Patient: Statin Therapy in Patients with Diabetes Reduced CV Risk (CARDS)

Relative CV Risk Reduction 37% (95% CI: –52 to –17)

Years

328

305

694

651

1074

1022

1361

1306

1392

1351

Atorvastatin

Placebo

1428

1410

Placebo127 CV events*

Atorvastatin83 CV events*

Cum

ulat

ive

haza

rd (%

)

0

5

10

15

0 1 2 3 4 4.75

P = 0.001

*CV events included stroke.CARDS = Collaborative Atorvastatin Diabetes Study.Colhoun HM et al. Lancet. 2004;364:685–696.

Page 36: Type 2 Diabetes:  Disease State Overview

Treating the Whole Patient: Patients Reaching Intensive Treatment Goals at 7.8 Years* (Steno-2)

Intensivetherapy (n = 80)†

Conventionaltherapy (n = 80)‡

A1C<6.5%

Patie

nts

(%)

20

30

40

50

60

70

10

80

Cholesterol<175 mg/dL

Triglycerides<150 mg/dL

Systolic BP<130 mmHg

Diastolic BP<80 mmHg

P = 0.06

P<0.001

P = 0.19

P = 0.001

P = 0.21

0

*Mean.†Intensive treatment included stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin.‡Conventional treatment was based on the Danish Medical Association guidelines.Gæde et al. N Engl J Med. 2003;348:383–393.

Page 37: Type 2 Diabetes:  Disease State Overview

Treating the Whole Patient: Intensive Therapy Reduced Composite Macrovascular Endpoints (Steno-2)

Prim

ary

com

posi

te e

ndpo

int*

(%)

0

0 3612

966048 847224

60

30

40

20

10

50

Intensive therapy

Conventional therapy

HR† = 0.47 (95% CI, 0.24-0.73)

53%

Months of Follow-up

*Composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease, P=0.007; †Unadjusted HR.CI = confidence interval; HR = hazard ratio.Gæde et al. N Engl J Med. 2003;348:383–393.

*Composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease, P=0.007; †Unadjusted HR.CI = confidence interval; HR = hazard ratio.Gæde et al. N Engl J Med. 2003;348:383–393.

Page 38: Type 2 Diabetes:  Disease State Overview

Treating the Whole Patient: a 5.5-Year* Follow-up (Steno-2) Intensive Therapy Sustains Cardiovascular Benefits

Cum

ulat

ive

Inci

denc

e of

Any

C

ardi

ovas

cula

r Eve

nt† (

%)

0

0 1

60

30

40

20

10

50

Intensive therapy

Conventional therapy

Years of Follow-up

*Mean. †Secondary composite endpoint of cardiovascular events, including death from cardiovascular causes, nonfatal stroke, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention, revascularization for peripheral atherosclerotic artery disease, and amputation.Gæde et al. N Engl J Med. 2008;358:580–591.

*Mean. †Secondary composite endpoint of cardiovascular events, including death from cardiovascular causes, nonfatal stroke, nonfatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention, revascularization for peripheral atherosclerotic artery disease, and amputation.Gæde et al. N Engl J Med. 2008;358:580–591.

2 3 4 5 6 7 8 9 10 11 12 13

70

80

HR 0.41(95% CI, 0.25 to 0.67; P<0.001)

59%

Page 39: Type 2 Diabetes:  Disease State Overview

*High risk patients are those with acute coronary syndromes or previous cardiovascular events.AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ADA = American Diabetes Association; EASD = European Association for the Study of Diabetes; HDL = high-density lipoprotein; LDL = low-density lipoprotein. 1. ADA Standards of Medical Care in Diabetes – 2009. Diabetes Care. 2009;32:S13–S61.2. American Association of Clinical Endocrinologists. Endocrine Practice. 2007;13(suppl 1):3–68.

Management of Type 2 Diabetes

• Type 2 diabetes requires a multifactorial approach for the management of glucose levels, blood pressure, and lipids to reduce complications1

• Recommendations for type 2 diabetes:

Lifestyle Modification

HypertensionDyslipidemia:

LDLDyslipidemia:

HDLHbA1c Goal

Combination therapy within 3 mo if not at HbA1c goal

ADA/EASD1 Target <130/80 mmHg

Target LDL <100 mg/dL

(<70 mg/dL for high-risk patients*)

Target HDL >40 mg/dL in men, >50 mg/dL in

women<7%

ACE/AACE2 Target<130/80 mmHg

Target LDL <100 mg/dL

(<70 mg/dL for high-risk patients*)

Target HDL >40 mg/dL in men, >50 mg/dL in

women≤6.5%

Page 40: Type 2 Diabetes:  Disease State Overview

Summary of Treatment Goals and Strategies

• Glycemic control is fundamental to the management of diabetes1

• The UKPDS demonstrated significant risk reductions in microvascular complications in type 2 diabetes with more intensive glycemic control. The benefit of A1C–lowering to reduce CVD in type 2 diabetes is supported by UKPDS data2

• There is a need to treat the whole patient, including management of hyperglycemia, CV risk factors and other comorbidities. This is key in reducing diabetes-related complications3

1. AACE. Endocr Pract. 2007;13(suppl 1):4–68. 2. Stratton IM et al. BMJ. 2000;321:405–412.3. American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12–S54.

Page 41: Type 2 Diabetes:  Disease State Overview

Conclusions:Management of Type 2 Diabetes

• Diabetes is a major clinical problem

– Pathophysiology involves insulin resistance and beta-cell dysfunction1

• Diabetes is correlated with increased risk of microvascular and macrovascular diseases and events

– Microvascular complications are predominately driven by hyperglycemia2,3

– Macrovascular complications are multifactorial and complex4

1. Kahn SE. J Clin Endocrinol Metab. 2001;86:4047–4058.2. AACE. Endocr Pract. 2007;13(suppl 1):4–68. 3. Stratton IM et al. BMJ. 2000;321:405–412.4. American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12–S54.

Page 42: Type 2 Diabetes:  Disease State Overview

Conclusions:Management of Type 2 Diabetes (cont)

• A1C reduction has been shown to reduce the risk of microvascular complications and may contribute to risk reduction of macrovascular endpoints1

• Early intervention is needed to get A1C to goal (diet and exercise should always be recommended)2

• It is challenging to maintain A1C control over time with traditional monotherapies3

• AACE and ADA* guidelines recommends use of combination therapy to achieve and sustain glycemic goals2,4

*ADA guidelines recommend that a second medication should be added within 3 months if patients are not at goal.1. Stratton IM et al. BMJ. 2000;321:405–412; 2. American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12–S54; 3. UKPDS. Lancet. 1998;352:854–865; 4. AACE. Endocr Pract. 2007;13(suppl 1):4–68.