CE on SUNDAY Newark, NJ October 18, 2009

Transcription

1 CE on SUNDAY Newark, NJ October 18, 2009 Date: Sunday, October 18, 2009 Time: 2:45 PM 3:45 PM Location: Sheraton Newark Airport Hotel Title: Speaker(s): Addressing Challenges in Type 2 Diabetes ACPE # L01-P CEU ACPE # L01-T CEU Financially supported by Merck & Co., Inc. Scott Stolte, Pharm.D., Shenandoah University Learning Objectives: Upon completion of this activity, participants will be able to: 1. Explain how the results of recent studies of diabetes medications can impact the care of your diabetic patients. 2. Communicate to patients the importance of reaching blood glucose goals and maintaining adherence and persistence. 3. Assist patients in interpreting and understanding A1C and average glucose values. Disclosures: Scott Stolte, Pharm.D., Shenandoah University declares no conflicts of interest or financial interests in any product or service mentioned in this program, including grants, employment, gifts, stock holdings, or honoraria. Speaker(s) Biography: Dr. Scott Stolte joined the faculty of the Bernard J. Dunn School of Pharmacy at Shenandoah University in Scott served as a faculty member and as Chair of the Department of Pharmacy Practice prior to assuming his position as Associate Dean for Academic Affairs. Dr. Stolte earned his Doctor of Pharmacy degree from Purdue University in West Lafayette, IN in After graduation, Dr. Stolte was the initial community pharmacy resident at Family PharmaCare, Inc. and Purdue University. Scott completed the American Association of Colleges of Pharmacy (AACP) Academic Leadership Fellowship program in While maintaining his interest in progressive community pharmacy practice and primary care disease state management, he has expanded his areas of teaching, service, and scholarship to include distance education, educational assessment, experiential education, and the application of leadership skills and traits to pharmacy and academic medicine.

2 Addressing Challenges in Type 2 Diabetes Scott Stolte, PharmD This program has been supported by an educational grant from Merck Pharmaceuticals PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education

3 Overview Impact of recent studies of diabetes medications on the care of your patients with diabetes Importance of reaching blood glucose goals. Interpreting and understanding A1C values

4 The Diabetes Epidemic 23.6 million US children and adults have diabetes million have pre- diabetes Prevalence 13.5% from million undiagnosed 17.9 million diagnosed 90-95% 95% Type 2 National Diabetes Statistics Fact Sheet Diabetes Care 2009;32(Suppl 1):S13-61.

5 Prevalence of Overweight in the U.S., 2006 CDC/NCHS, Health, United States, 2006

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7 Prevalence of Diabetes in the U.S., 2005 National Diabetes Surveillance System

8 Case 1 (Arnie) A 46-year-old Caucasian male with a family history of type 2 diabetes, who presented requesting a screening test to see if he had diabetes. no symptoms of diabetes but had gained approximately 30 lbs over the past 10 years. no formal exercise regimen height = 6 1, weight= 228 lbs, BMI = 30.1 kg/m 2 BP = 138/84 mm Hg

9 Natural History of Type 2 Diabetes Prediabetes/IGT/IFG T2DM Postprandial glucose Glucose Fasting glucose 126 mg/dl Relative Function 100% Insulin level Beta-cell function Insulin resistance hepatic and peripheral Years from Diabetes Diagnosis IGT=impaired glucose tolerance; IFG=impaired fasting glucose. Diabetes Care 1992;15:815-9.

10 Screening for Type 2 Diabetes Overweight (BMI 25 kg/m 2 ) and additional risk factors: Physical inactivity First-degree relative with diabetes Hypertension HDL cholesterol level <35 mg/dl Triglyceride gy level >250 mg/dl Women with PCOS History of IGT or IFG History of CVD PCOS, polycystic ovarian syndrome IGT, impaired glucose tolerance IFG, impaired fasting glucose CVD, cardiovascular disease Diabetes Care 2009;32(Suppl 1):S13-61.

11 Screening for Type 2 Diabetes Overweight (BMI 25 kg/m 2 ) and additional risk factors: Members of a high-risk ethnic population p (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Women who delivered a baby weighing >9 lb or were diagnosed with gestational DM Clinical conditions associated with insulin resistance (severe obesity, acanthosis nigricans) Diabetes Care 2009;32(Suppl 1):S13-61.

12 Acanthosis Nigricans

13 Screening for Type 2 Diabetes in Children Overweight (BMI >85th percentile for age and gender or weight >120% of ideal for height) Plus any two of the following risk factors: Family history of type 2 diabetes in first or second- degree relative Race/ethnicity (Native American, African American, Latino, Asian American, Pacific Islander) Signs of insulin resistance or conditions associated with insulin resistance Maternal history of diabetes or GDM Diabetes Care 2009;32(Suppl 1):S13-61.

14 Case Study - Should Arnie be screened? Family history (? 1st degree relative) Overweight

15 Types of Screening Programs Self done - Will depend on state regulations Outside screening company Off site - Health fairs, wellness centers, senior centers, workplace Referral to community screening (co- promotion?)

16 Interpreting Screening Results IFG = fasting plasma glucose mg/dl IGT = 2-h plasma glucose mg/dl Diabetes FPG 126 mg/dl 2-h plasma glucose 200 mg/dl + symptoms Oral glucose tolerance test 200 mg/dl Refer anyone with abnormal values for follow-up Diabetes Care 2009;32(Suppl 1):S13-61.

17 Why It Is Important To Screen Large number of people are thought to be undiagnosed Damage occurs before symptoms Increasing weight of US population is increasing DM prevalence

18 Case2(Bernice) A 75 yr old, recently widowed and lives alone in high rise senior apartment complex History of HTN, osteoporosis (hip fracture 1 yr ago), DM (diagnosed 1 yr ago) Metformin 850 mg bid A1C = 8% Drives to social activities and for activities of daily living

19 What is A1C and Why is it Important? Glycated or glycosylated hemoglobin HbA1C, A1C Normal range: 4.0% to 6.7% Reflects mean glucose levels l over preceding 120 days Elevated in: Uncontrolled diabetes mellitus, lead toxicity, alcoholism, iron deficiency anemia, hypertriglyceridemia Difficult for patients to understand

20 It s Not Just Confusing for Newly Diagnosed Patients High levels of testing of HbA1c for patients with known diabetes (> 90%) Of patients with test in past 6 months: 66% did not know result 25% accurately reported within 1% range (< 7%, 7-8%, 8-9%) 9% inaccurately reported within 1% range Diabetes Care 2005;28:

21 The A1C-Derived Average Glucose (ADAG) Study Carefully look at relationship between HbA1c and average glucose Determine the mathematical relationship between the two for reliable conversion Establish that the relationship is valid across: Diabetes types A wide range of HbA1c levels and age Different races/ethnicities Diabetes Care 2008;31:

22 ADAG Study: Correlation of AG With HbA1c AG (m mg/dl) AG (mg/dl) = 28.7 x HbA1c 46.7 R2 = 0.84 P < HbA1c (%) Diabetes Care 2008;31:

23 Estimated Average Glucose (eag) Linear relationship between A1C and average blood glucose levels ADA now recommends reporting A1C to patients as eag (but call it Average glucose) Online calculator - org/glucosecalculator aspx AG (mg/dl) = (28.7 x HbA1c) 46.7

24 Average Glucose Blood pressure Cholesterol to help make the A understandable!

25 Mean Plasma Glucose ( Average Glucose ) A1C (%) Mean plasma glucose mg/dl mmol/l Diabetes Care 2009;32(Suppl 1):S13-61.

26 Current Treatment Guidelines Biochemical Index Normal ADA ACE/AACE Goal Goal Fasting/preprandial plasma glucose (mg/dl) < < 110 Postprandial <120 <180 < 140 plasma glucose (mg/dl) A1C (%) <6 < Average Glucose (mg/dl) < 126 < ADA = American Diabetes Association ACE/AACE = American College of Endocrinology/American Association of Clinical Endocrinologists Diabetes Care 2009;32(Suppl 1):S Endocr Pract 2002;8(Suppl 1):43-65.

27 GOOD GLYCEMIC CONTROL: A CRITICAL GOAL Each 1% reduction in mean A1C Reduces risk of death from diabetes by 21% Reduces risk of microvascular complications by 37% Reduces risk of heart attack by 14% UKPDS 35 BMJ 2000:321:

28 GOOD GLYCEMIC CONTROL: A CRITICAL BUT ELUSIVE GOAL A1C Goal Achievement 36% >7% 64% < 7% Diabetes Care 2004;27:17-20.

29 GOOD GLYCEMIC CONTROL: A CRITICAL BUT ELUSIVE GOAL Multiple factors continue to challenge goal achievement: Natural progression of beta-cell dysfunction with increasing hyperglycemia gy Lack of long term adherence with lifestyle issues (medical nutrition therapy & exercise) and medications Provider beliefs

30 Recent Trials in Type 2 DM - ACCORD 10,251 subjects, median 8 yrs of disease, target A1C <6%, 3.4 yr trial Median A1C 6.4% (intensive) vs 7.5%(standard) 90% in intensive i treatment t t group received rosiglitazone vs 58% of standard group 50% had documented macrovascular disease (35% prior CV event), rest had multiple CV risk factors N Engl J Med 2008;358:

31 Recent Trials in Type 2 DM - ACCORD Only 75% on aspirin Higher incidence of hypoglycemia, gy heart failure, weight gain, and fluid retention in intensive group -- 28% gained more than 22 lbs N Engl J Med 2008;358:

32 ACCORD Results Intensive Therapy Standard Therapy HR P value (n=5,128) (n=5,123) Primary Outcome 352 (6.9%) 371 (7.2%) 0.90 P=0.16 Death from any cause 257 (5.0%) 203 (4.0%) 1.22 P=0.04 CV mortality 135 (2.6%) 94 (1.8%) 1.35 P=0.02 Primary outcome - composite nonfatal MI, nonfatal stroke, or death from CV cause HR, hazard ratio N Engl J Med 2008;358:

33 Recent Trials in Type 2 DM - ADVANCE Effects of intensive glucose control on vascular outcomes 11,140 patients, mean 8 yrs of disease Intensive e (A1C 6.5%) vs standard therapy over 5 years Median A1C 6.4 vs 7.0 Gliclazide (modified release) and other meds as required N Engl J Med 2008;358:

34 Advance Results Intensive better Standard better N Engl J Med 2008;358:

35 Recent Trials in Type 2 DM - VDAT Effects of intensive glucose control on cardiovascular events in patients with long- standing type 2 diabetes mellitus 1791 veterans not at goal mean age = 60.4 years mean number of years since the diagnosis i of diabetes = % of the patients had already had a cardiovascular event N Engl J Med 2009;360:

36 VDAT Median follow-up = 5.6 years Median HgA1C = 8.4% (standard-therapy) therapy) vs 6.9% (intensive-therapy). therapy). Major CV event = 264 (standard) vs 235 (intensive) [95% confidence interval [CI], 0.74 to 1.05; P=0.14] Hypoglycemia = 17.6% (standard) vs 24.1% intensive) N Engl J Med 2009;360:

37 United Kingdom Prospective Diabetes Study 10 yr followup data from UKPDS 4209 newly diagnosed Type 2 received conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) No attempt to maintain assigned treatment in long term followup N Engl J Med 2008;359:

38 United Kingdom Prospective Diabetes Study Relative Risk Reduction Treatment Any Microvascular Myocardial Death from Group diabetes- disease infarction any cause related end point Sulfonylurea 9%, 24%, 15%, 13%, -insulin P=0.04 P=0.001 P=0.01 P=0.007 group Metformin 21%, NR 33%, 27%, group P=0.01 P=0.005 P=0.002 N Engl J Med 2008;359:

39 Bottom Line A1C goal should be adjusted based on patient characteristics/risks of hypoglycemia Aggressive goals are probably better for younger patients Once disease has been present for many yy years, aggressive lowering is not going to reverse macrovascular disease and may increase risk of adverse effects

40 Case Study - Should Bernice s At 8% A1C be lower? Risks from hypoglycemia No evidence of macrovascular disease

41 Case 3 (Hector) A 42 year old construction worker DM, hyperlipidemia, HTN, obesity A1C = 7.5%, fasting glucose (ADA ) Recently started checking 2 hr post-prandial glucose - averaging 200 mg/dl after breakfast and dinner, lunch 180 mg/dl (ADA < 180 mg/dl)

42 Which of the following can be caused by postprandial hyperglycemia? Microvascular disease Increased triglycerides Prothrombiotic state Cardiovascular disease All of the above

43 Why Care about Postprandial Hyperglycemia? Coagulation CVD Hyper TG Oxidative Stress PPHG Microvascular disease Increased Inflammatory Markers risk of death Oxidized LDL

44 Lancet 1999;354:

45 Patients With Type 2 Diabetes May Spend 12 Hours per Day in the Postprandial State Duration of Postprandial State Postprandial Postabsorptive Fasting Breakfast Lunch Dinner Midnight 4 AM Breakfast 8 AM 11 AM 2 PM 5 PM Times of blood sampling to obtain a diurnal blood glucose profile Eur J Clin Invest. 2000;30(suppl 2):3-11.

46 Increasing Contribution of PPG as A1C Improves % Contribution n FPG PPG > <7.3 A1C Range (%) FPG = fasting plasma glucose PPG = post prandial glucose Diabetes Care 2003;26:

47 Importance of Postprandial Hyperglycemia IGT is a risk factor for cardiovascular disease Contributes more to A1C than FPG at A1Cs < 7.3% Can be rate limiting factor for achieving adequate gy glycemic control Diabetolgia 2002;45: Diabetes Care 1999;22:

48 Agents that Target Postprandial Glucose Alpha-glucosidase Miglitol (Glyset ) inhibitors Acarbose (Precose ) Meglitinides Repaglinide (Prandin ) Nateglinide (Starlix ) Rapid-acting insulin Insulin lispro (Humalog ) Insulin aspart (NovoLog ) Insulin glulisine (Apidra ) Incretin agents Exenatide (Byetta ) Pramlintide (Symlin ) DDP4 inhibitors Sitagliptin (Januvia ) Sitagliptin/Metformin (Janumet )

49 Case Study - Does Hector need an increase in his diabetes medications? A1C = 7.5% (AG = 168 mg/dl) 2 hr postprandial - averaging 200 mg/dl after breakfast and dinner, lunch 180 mg/dl

50 Conclusions Important to screen likely candidates for diabetes and get them into treatment Patients need average glucose or A1C goals and need to understand the importance of reaching these goals How aggressive to be will depend on patient factors Translate A1C to average glucose Target elevated postprandial glucose