Management of Hyperglycemia in Type 2 - 1.

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Writing Group
American Diabetes Association Richard M. Bergenstal MD
Intl Diabetes Center, Minneapolis, MN
European Assoc. for the Study of Diabetes Michaela Diamant MD, PhD
VU University, Amsterdam, The Netherlands
John B. Buse MD, PhD

University of North Carolina, Chapel Hill, NC
Ele Ferrannini MD
University of Pisa, Pisa, Italy
Anne L. Peters MD
Univ. of Southern California, Los Angeles, CA
Michael Nauck MD
Diabeteszentrum, Bad Lauterberg, Germany
Richard Wender MD
Thomas Jefferson University, Philadelphia, PA
Apostolos Tsapas MD, PhD

Aristotle University, Thessaloniki, Greece
Silvio E. Inzucchi MD (co-chair)

Yale University, New Haven, CT
David R. Matthews MD, DPhil (co-chair)

Oxford University, Oxford, UK
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach
1. PATIENT-CENTERED APPROACH 2. BACKGROUND

Epidemiology and health care impact Relationship of glycemic control to outcomes Overview of the pathogenesis of Type 2 diabetes
3. ANTI-HYPERGLYCEMIC THERAPY
Glycemic targets Therapeutic options
- Lifestyle
- Oral agents & non-insulin injectables - Insulin
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach
3. ANTIHYPERGLYCEMIC THERAPY
Implementation Strategies - Initial drug therapy

- Advancing to dual combination therapy - Advancing to triple combination therapy - Transitions to and titrations of insulin
4. OTHER CONSIDERATIONS
Age Weight Sex/racial/ethnic/genetic differences Comorbidities (Coronary artery disease, Heart failure, Chronic kidney disease, Liver dysfunction, Hypoglycemia)
5. FUTURE DIRECTIONS / RESEARCH NEEDS

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM
1. Patient-Centered Approach
...providing care that is respectful of and responsive to individual patient preferences, needs, and values - ensuring that patient values guide all clinical decisions.
Gauge patients preferred level of involvement. Explore, where possible, therapeutic choices. Utilize decision aids. Shared decision making final decisions re: lifestyle choices
ultimately lies with the patient.
2. BACKGROUND
Epidemiology and health care impact
Obesity (BMI 30 kg/m2)
Age-adjusted Percentage of U.S. Adults with Obesity or Diagnosed Diabetes

1994 2000 2009
O O B B E E S S II T T Y Y
Diabetes
No Data
<14.0%
14.0-17.9%
18.0-21.9%
22.0-25.9%
>26.0%
D D II A A B B E E T T E E S S
1994
2000
2009
No Data
<4.5%
4.5-5.9%
6.0-7.4%
7.5-8.9%
>9.0%
CDCs Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics
The Diabetes Epidemic: Global Projections, 20102030
IDF. Diabetes Atlas 5th Ed. 2011
2. BACKGROUND
Relationship of glycemic control to outcomes
Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials

Study
UKPDS DCCT / EDIC* ACCORD ADVANCE VADT
Kendall DM, Bergenstal RM. International Diabetes Center 2009 UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854. Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977. Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545. Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum: Moritz T. N Engl J Med 2009;361:1024)
Microvasc
CVD
Mortality

Initial Trial Long Term Follow-up * in T1DM
2. BACKGROUND
Overview of the pathogenesis of T2DM
- Insulin secretory dysfunction -Insulin resistance (muscle, fat, liver) -Increased endogenous glucose production -Deranged adipocyte biology -Decreased incretin effect
Main Pathophysiological Defects in T2DM

incretin effect pancreatic insulin secretion
pancreatic glucagon secretion
gut carbohydrate delivery & absorption
HYPERGLYCEMIA
hepatic glucose production
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

+ + + + + + + +
peripheral glucose uptake
Glycemic targets
- HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l]) - Pre-prandial PG <130 mg/dl (7.2 mmol/l) - Post-prandial PG <180 mg/dl (10.0 mmol/l) - Individualization is key:
Tighter targets (6.0 - 6.5%) - younger, healthier Looser targets (7.5 - 8.0%+) - older, comorbidities, hypoglycemia prone, etc.
- Avoidance of hypoglycemia
PG = plasma glucose
Figure 1
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] (Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)
Therapeutic options: Lifestyle

- Weight optimization - Healthy diet
- Increased activity level

Therapeutic options:
Oral agents & non-insulin injectables
- Metformin - Sulfonylureas - Thiazolidinediones - DPP-4 inhibitors - GLP-1 receptor agonists
- Meglitinides - -glucosidase inhibitors - Bile acid sequestrants - Dopamine-2 agonists - Amylin mimetics
Class
Biguanides
Mechanism
Activates AMP-kinase Hepatic glucose production Closes KATP channels Insulin secretion
Advantages
Extensive experience No hypoglycemia Weight neutral ? CVD Extensive experience Microvasc. risk
Disadvantages
Gastrointestinal Lactic acidosis B-12 deficiency Contraindications Hypoglycemia Weight gain Low durability ? Ischemic preconditioning
Cost
Low
SUs / Meglitinides
Low
TZDs
PPAR- activator insulin sensitivity
No hypoglycemia Durability TGs, HDL-C ? CVD (pio)
Weight gain High Edema / heart failure Bone fractures ? MI (rosi) ? Bladder ca (pio) Mod.
-GIs
Inhibits glucosidase Slows carbohydrate absorption
No hypoglycemia Gastrointestinal Nonsystemic Dosing frequency Post-prandial glucose Modest A1c ? CVD events
Table 1. Properties of anti-hyperglycemic agents
Class
DPP-4 inhibitors GLP-1 receptor agonists Amylin mimetics
Mechanism
Inhibits DPP-4 Increases GLP-1, GIP Activates GLP-1 R Insulin, glucagon gastric emptying satiety Activates amylin receptor glucagon gastric emptying satiety Bind bile acids Hepatic glucose production
Advantages
No hypoglycemia Well tolerated Weight loss No hypoglycemia ? Beta cell mass ? CV protection Weight loss PPG
Disadvantages
Modest A1c ? Pancreatitis Urticaria GI ? Pancreatitis Medullary ca Injectable GI Modest A1c Injectable Hypo w/ insulin Dosing frequency
Cost
High
High
High
Bile acid sequestrants
No hypoglycemia GI Nonsystemic Modest A1c Post-prandial glucose Dosing frequency CVD events Modest A1c Dizziness/syncope Nausea Fatigue
High
Dopamine-2 agonists
Activates DA receptor No hypoglyemia Modulates hypothalamic ? CVD events control of metabolism insulin sensitivity
High
Class
Insulin
Mechanism
Activates insulin receptor peripheral glucose uptake
Advantages
Universally effective Unlimited efficacy Microvascular risk
Disadvantages
Hypoglycemia Weight gain ? Mitogenicity Injectable Training requirements Stigma
Cost
Variable
Therapeutic options: Insulin

- Neutral protamine Hagedorn (NPH) - Regular - Basal analogues (glargine, detemir) - Rapid analogues (lispro, aspart, glulisine) - Pre-mixed varieties
Therapeutic options: Insulin

Rapid (Lispro, Aspart, Glulisine) Insulin level Short (Regular) Intermediate (NPH) Long (Detemir) Long (Glargine) 0 2 4 6 8 10 12 14 16 18 20 22 24 Hours after injection
Hours
Implementation strategies:
- Initial therapy - Advancing to dual combination therapy - Advancing to triple combination therapy - Transitions to & titrations of insulin
T2DM Antihyperglycemic Therapy: General Recommendations
Diabetes Care, Diabetologia. 19 April 201 Diabetologia.
[Epub ahead of print] [Epub
Insulin Strategies in T2DM
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] Diabetologia. [Epub
Age Weight Sex / racial / ethnic / genetic differences Comorbidities
Coronary artery disease Heart Failure Chronic kidney disease Liver dysfunction Hypoglycemia
Age: Older adults
Reduced life expectancy Higher CVD burden Reduced GFR At risk for adverse events from polypharmacy More likely to be compromised from hypoglycemia
Less ambitious targets HbA1c <7.58.0% if tighter targets not easily achieved Focus on drug safety
Weight
Majority of T2DM patients overweight / obese Intensive lifestyle program Metformin GLP-1 receptor agonists ? Bariatric surgery Consider LADA in lean patients
T2DM Anti-hyperglycemic Therapy: General Recommendations
Diabetes Care, Diabetologia. 19 April 2012 Diabetologia. [Epub ahead of print]
Adapted Recommendations: When Goal is to Avoid Weight Gain
Sex/ethnic/racial/genetic differences
- Little is known - MODY & other monogenic forms of diabetes - Latinos: more insulin resistance - East Asians: more beta cell dysfunction - Gender may drive concerns about adverse effects (e.g., bone loss from TZDs)
Comorbidities
- Coronary Disease - Heart Failure - Renal disease - Liver dysfunction - Hypoglycemia Metformin: CVD benefit (UKPDS) Avoid hypoglycemia ? SUs & ischemic preconditioning ? Pioglitazone & CVD events ? Effects of incretin-based therapies
Comorbidities
- Coronary Disease - Heart Failure - Renal disease - Liver dysfunction - Hypoglycemia Metformin: May use unless condition is unstable or severe Avoid TZDs ? Effects of incretin-based therapies
Comorbidities
- Coronary Disease - Heart Failure - Renal disease - Liver dysfunction - Hypoglycemia Increased risk of hypoglycemia Metformin & lactic acidosis US: stop @SCr 1.5 (1.4 women) UK: dose @GFR <45 & stop @GFR <30 Caution with SUs (esp. glyburide) DPP-4-is dose adjust for most Avoid exenatide if GFR <30
Comorbidities
- Coronary Disease - Heart Failure - Renal disease - Liver dysfunction - Hypoglycemia Most drugs not tested in advanced liver disease Pioglitazone may help steatosis Insulin best option if disease severe
Comorbidities
- Coronary Disease - Heart Failure - Renal disease - Liver dysfunction - Hypoglycemia Emerging concerns regarding association with increased mortality Proper drug selection in the hypoglycemia prone
T2DM Anti-hyperglycemic Therapy: General Recommendations
Adapted Recommendations: When Goal is to Avoid Hypoglycemia
Adapted Recommendations: When Goal is to Minimize Costs
Guidelines for Glycemic, BP, & Lipid Control

American Diabetes Assoc. Goals
HbA1C Preprandial glucose Postprandial glucose Blood pressure
< 7.0% (individualization) 70-130 mg/dL (3.9-7.2 mmol/l) < 180 mg/dL < 130/80 mmHg LDL: < 100 mg/dL (2.59 mmol/l) < 70 mg/dL (1.81 mmol/l) (with overt CVD) HDL: > 40 mg/dL (1.04 mmol/l) > 50 mg/dL (1.30 mmol/l) TG: < 150 mg/dL (1.69 mmol/l)
ADA. Diabetes Care. 2012;35:S11-63
Lipids
HDL = high-density lipoprotein; LDL = low-density lipoprotein; PG = plasma glucose; TG = triglycerides.
4. FUTURE DIRECTIONS / RESEARCH NEEDS
Comparative effectiveness research

Focus on important clinical outcomes
Contributions of genomic research Perpetual need for clinical judgment!
KEY POINTS
Glycemic targets & BG-lowering therapies must individualized.
Diet, exercise, & education: foundation of any T2DM therapy education program Unless contraindicated, metformin = optimal 1st-line drug. After metformin, data are limited. Combination therapy with 1-2 other oral / injectable agents is reasonable; minimize side effects. Ultimately, many patients will require insulin therapy alone / in combination with other agents to maintain BG control. All treatment decisions should be made in conjunction with the patient (focus on preferences, needs & values.) Comprehensive CV risk reduction - a major focus of therapy.
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] Diabetologia. [Epub
Invited Reviewers
James Best, The University of Melbourne, AU Henk Bilo, Isala Clinics, Zwolle, NL John Boltri, Wayne State University, Detroit, MI Thomas Buchanan, Univ of So California, LA, CA Paul Callaway, University of Kansas,Wichita, KS Bernard Charbonnel, University of Nantes, France Stephen Colagiuri, The University of Sydney, AS Samuel Dagogo-Jack, Univ of Tenn, Memphis, TN Margo Farber, Detroit Medical Center, Detroit, MI Cynthia Fritschi, University of Illinois, Chicago, IL Rowan Hillson, Hillingdon Hospital, Uxbridge, U.K. Faramarz Ismail-Beigi, CWR Univ, Cleveland, OH Devan Kansagara, Oregon H&S Univ, Portland, OR Ilias Migdalis, NIMTS Hospital, Athens, Greece Donna Miller, Univ of So California, LA, CA Robert Ratner, MedStar/Georgetown Univ, DC Julio Rosenstock, Dallas Diab/Endo Ctr, Dallas, TX Guntram Schernthaner, Rudolfstiftung Hosp, Vienna, AT Robert Sherwin, Yale University, New Haven, CT Jay Skyler, University of Miami, Miami, FL Geralyn Spollett, Yale University,New Haven, CT Ellie Strock, Intl Diabetes Center, Minneapolis, MN Agathocles Tsatsoulis, University of Ioannina, GR Andrew Wolf, Univ of Virginia Charlottesville, VA Bernard Zinman, University of Toronto, CA
Professional Practice Committee, American Diabetes Association Panel for Overseeing Guidelines and Statements, European Association for the Study of Diabetes American Association of Diabetes Educators The Endocrine Society American College of Physicians

Management of Hyperglycemia in Type 2 - 1.

Uploaded by

Document Information

Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Description:

Copyright:

Available Formats

Management of Hyperglycemia in Type 2 - 1.

Original Title:

Uploaded by

Description:

Copyright:

Available Formats

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach

John B. Buse MD, PhD

Apostolos Tsapas MD, PhD

Silvio E. Inzucchi MD (co-chair)

David R. Matthews MD, DPhil (co-chair)

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach

1. PATIENT-CENTERED APPROACH 2. BACKGROUND

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach

Implementation Strategies - Initial drug therapy

5. FUTURE DIRECTIONS / RESEARCH NEEDS

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Obesity (BMI 30 kg/m2)

Age-adjusted Percentage of U.S. Adults with Obesity or Diagnosed Diabetes

The Diabetes Epidemic: Global Projections, 20102030

IDF. Diabetes Atlas 5th Ed. 2011

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Relationship of glycemic control to outcomes

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Overview of the pathogenesis of T2DM

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Main Pathophysiological Defects in T2DM

gut carbohydrate delivery & absorption

hepatic glucose production

Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

peripheral glucose uptake

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Therapeutic options: Lifestyle

- Increased activity level

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

- Metformin - Sulfonylureas - Thiazolidinediones - DPP-4 inhibitors - GLP-1 receptor agonists

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

PPAR- activator insulin sensitivity

No hypoglycemia Durability TGs, HDL-C ? CVD (pio)

Inhibits glucosidase Slows carbohydrate absorption

Table 1. Properties of anti-hyperglycemic agents

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Bile acid sequestrants

Table 1. Properties of anti-hyperglycemic agents

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Table 1. Properties of anti-hyperglycemic agents

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Therapeutic options: Insulin

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Therapeutic options: Insulin

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

T2DM Antihyperglycemic Therapy: General Recommendations

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

T2DM Antihyperglycemic Therapy: General Recommendations

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

T2DM Antihyperglycemic Therapy: General Recommendations

Diabetes Care, Diabetologia. 19 April 201 Diabetologia.