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New Perspectives in the Management of Type 2 Diabetes Herold Merisier, MD, FAAFP Voluntary Assistant Professor of Family Medicine Miller School of Medicine, University of Miami Plantation, FL Disclosure Speaker: Novartis Pharmaceuticals Speaker: Novo-Nordisk Diabetes 2010 Epidemiology Diagnosis Screening Management of Type 2 Diabetes Patient Education Therapeutic Lifestyle Changes (TLC) Pharmacotherapy Treatment of co-morbid conditions Diabetes in the US 23.6 million children and adults affected (7.8% of the population) Diagnosed: 17.9 million people Undiagnosed: 5.7 million people 1.6 million new cases in adults > 20y/o in 2007 4300 new cases every day Pre-Diabetes: 57 million people 2-4 fold increase in cardiovascular mortality and stroke Center for Disease Control and Prevention Available at: http://www.cdc.gov/diabetes/pubs/estimates07.htm#1 Diabetes in Canada 1.8 million adults with Diabetes Prevalence: 4.8% (1998): 1 054 000 adult Canadians Prevalence: 5.5% (2005) Available at: http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf Global Projections for the Diabetes Epidemic: 2003-2025 NA EUR 23.0 M 36.2 M ↑57.0% 48.4 M 58.6 M ↑21% EMME WP 19.2 M 39.4 M ↑105% SEA 39.3 M 81.6 M ↑108% AFR SACA World 2003 = 194 M 2025 = 333 M ↑ 72% 14.2 M 26.2 M ↑85% 7.1M 15.0 M ↑111% 2003 2025 M = million, AFR = Africa, NA = North America, EUR = Europe, SACA = South and Central America, EMME = Eastern Mediterranean and Middle East, SEA = South-East Asia, WP = Western Pacific Diabetes Atlas Committee. Diabetes Atlas 2nd Edition: IDF 2003. 43.0 M 75.8 M ↑79% Diagnosis Normoglycemia FPG < 100 mg/dl 2hPPG < 140 mg/dl Impaired Glucose Metabolism FPG ≥ 100 mg/dl < 126 mg/dl IFG 2hPPG ≥ 140 mg/dl < 200 mg/dl IGT Diabetes FPG ≥ 126 mg/dl (x 2) 2hPPG ≥ 200 mg/dl or RPG ≥ 200 mg/dl w/ sx of Diabetes HbA1c ≥ 6.5 (x 2) IFG: Impaired Fasting Glucose Glucose IGT: Impaired Glucose Tolerance FPG: Fasting Plasma Glucose RPG: Random Plasma PPG: Post-Prandial Glucose Adapted from Clinical Practice Recommendations. Diabetes Care, 2010 Screening All individuals ≥ 45y/o, particularly if BMI ≥ 25 if normal, repeat every 3 years Start screening at younger age if BMI ≥ 25 and: physically inactive first-degree relative with Diabetes high risk ethnic group h/o IFG, IGT, Gestational Diabetes, PCOS Dyslipidemia or h/o cardio-vascular disease Fasting glucose or 2-hour OGTT Diabetes Risk Calculator Diabetes Risk Calculator Gender Age Prior history of elevated blood glucose Height and weight Diet Smoking history Physical activity Family history Diabetes Care. 2008 May;31(5):1040-5 Diabetes Risk Calculator Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/ Diabetes Risk Calculator Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/ QD Score (http://www.qdscore.org) BMJ 2009;338:b880. Available at: http://bmj.com/cgi/content/full/338/mar17_2/b880 Management of Type 2 Diabetes Patient Education Therapeutic Lifestyle Changes (TLC) Pharmacotherapy Treatment of co-morbid conditions Pharmacotherapy: Oral Agents Class Drugs Mechanism of action α-Glucosidase Inhibitor Acarbose Miglitol Decrease carbohydrate absorption in GI tract Biguanides Metformin Decrease hepatic neoglucogenesis Secretagogues Sulfonylureas Meglitinides Glyburide, Glipizide, Glimepiride Repaglinide, Nateglinide Stimulate β-cell to increase insulin output Thiazolidinediones Pioglitazone (Actos®) Rosiglitazone (Avandia®) Improve insulin sensitivity, decrease insulin resistance DDP-4 Inhibitors Sitagliptin (Januvia®) Saxagliptin (Onglyza®) Slow incretin metabolism, Increase insulin synthesis/release, Decrease glucagon levels DPP-4 Inhibitors Rosiglitazone (Avandia®) Contraindicated in patients with CHF Meta-analysis of 42 clinical studies: Mean duration 6 months; 14,237 total patients Rosiglitazone vs. placebo Increased risk of risk of myocardial ischemic events Three other studies Mean duration 41 months; 14,067 total patients Rosiglitazone vs. other oral diabetes medications or placebo Increased of MI neither confirmed nor excluded this risk Progressive -cell Failure in Type 2 Diabetes 100 Diagnosis 80 60 40 20 0 -12 -6 0 6 12 Years Based on data of UKPDS 16: conventional (diet) treatment group. Diabetes. 1995. 18 Pharmacotherapy: Non-Insulin Injectables Class Drug Mechanism of action increases beta-cell Exenatide (Byetta®) response GLP-1 Analog decreases glucagon (Incretin Mimetic) Liraglutide (Victoza®) secretion delays gastric emptying slows gastric emptying decreases glucagon Amlynomimetic Pramlintide (Symlin®) secretion early satiety → weight loss Pharmacotherapy: Insulin (Older Agents) Insulin Preparation Onset Peak Duration Short acting Regular 30-60 min. 3-4h 6-8h Intermediate NPH Lente Ultralente 2-4h 3-4h 4-6h 6-10h 6-12h 10-16h 14-18h 16-20h 20-24h 30-60 min. 15-60 min. Dual Dual 14-18h 14-18h Combinations 70% NPH / 30% reg 75% NPH / 25% reg Pharmacotherapy: Insulin (Newer Agents: Insulin Analogs) Insulin Preparation Rapid acting Lispro (Novolog®) Aspart (Humalog®) Glulisine (Apidra®) Long acting Glargine (Lantus®) Detemir (Levemir®) Combinations 70% / 30% lispro 75% / 25% aspart 50% / 50% aspart Onset Peak Duration 15-30 min. 15-30 min. 15-30 min. 30-90 min. 30-90 min. 30-90 min. 4-6h 4-6h 4-6h 1-2h 1-2h flat flat 24h 24h 30-60 min. 15-60 min. 15-60 min. Dual Dual Dual 14-18h 14-18h 14-18h Therapy for Type 2 Diabetes: Sites of Action Adipose tissue Pancreas Sulfonylureas Repaglinide TZD Glucose Gut Glucose uptake Rosiglitazone Pioglitazone -Glucosidase inhibitors Hyperglycemia HGO* Liver Metformin Thiazolidinediones Acarbose Miglitol Muscle Metformin Thiazolidinediones *HGO=hepatic glucose output. Adapted from DeFronzo RA. Ann Intern Med. 1999;131:281-303. Package Inserts for AVANDIA® (rosiglitazone maleate, GlaxoSmithKline), Actos® (pioglitazone HCl, Takeda), Prandin® (repaglinide, Novo Nordisk), Precose® (acarbose tablets, Bayer), Glyset® (miglitol, mfd. by Bayer for Pharmacia & Upjohn). Stepwise Management of Type 2 Diabetes + + + Adapted from Williams G. Lancet 1994; 343: 95-100. 23 Pharmacotherapy Stepwise Management Glycemic targets often not met Monotherapy often not effective long term Therapy fails to address multiple impairments Step-wise approach tends to perpetuate “failure” New Treatment Paradigm Treatment designed to address multiple impairments Simultaneous rather than sequential therapy Combination therapy from the outset Early titrations to meet glycemic targets Combination Oral Diabetic Agents Glucovance® ( Glyburide + Metformin) Metaglip® (Glipizide + Metformin) Avandamet® (Rosiglitazone + Metformin) Avandaryl® (Rosiglitazone + Glimepiride) ActoPlus Met® (Pioglitazone + Metformin) Janumet® (Januvia + Metformin) ADA/EASD Consensus Algorithm 2009 Step 1 Step 2 Step 3 Tier 1: Well-validated core therapies At Diagnosis Lifestyle + Metformin Lifestyle + Metformin + Basal Insulin Lifestyle + Metformin + Sulfonylurea Tier 2: Less well validated therapies Lifestyle + Metformin + Pioglitazone Lifestyle + Metformin + GLP1- Agonist Lifestyle + Metformin + Intensive Insulin Lifestyle + Metformin + Pioglitazone + Sulfonylurea Lifestyle + Metformin + Basal Insulin Nathan and Associates: Diabetes Care, Vol. 32, Number 1, January 2009 ACCE Diabetes Algorithm 2009 Glycemic Control Algorithm, Endocr Pract. 2009;15(No. 6) Glucose Dynamics: Basal and Prandial 250 Postprandial hyperglycemia 200 Plasma glucose (mg/dL) Type 2 diabetes 150 Basal hyperglycemia 100 50 Normal 0 0600 1200 1800 Time of day Riddle MC. Am J Med. 2004;116(suppl):3S-9. 2400 0600 Basal-Bolus Combination Therapy Breakfast Bolus insulin Plasma Insulin Levels Lunch Bolus insulin Dinner Bolus insulin Basal insulin 4:00 8:00 12:00 16:00 Time 20:00 24:00 4:00 8:00 Treatment of co-morbid conditions Dyslipidemia Hypertension Diabetes CV Risk Calculator Available at: http://www.dtu.ox.ac.uk/riskengine/ Diabetes CV Risk Calculator (Canada) http://www.diabetes.ca/documents/about-diabetes/FINAL_PATIENT_TOOL_FOR_WEBSITE.pdf The ABCs of Diabetes Care A1C ADA recommends < 7% in general, < 6% for selected individuals AACE/IDF recommend ≤ 6.5% Blood pressure < 130/80 mm Hg Cholesterol LDL-C: < 100 mg/dL (< 70 mg/dL in very high-risk patients) HDL-C: > 40 mg/dL in men and > 50 mg/dL in women Non-HDL-C: < 130 mg/dL (< 100 mg/dL in high-risk patients) Triglycerides: < 150 mg/dL American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4-S41. American Association of Clinical Endocrinologists. Endocr Pract. 2007;13(suppl 1):3-68. International Diabetes Federation. Diabet Med. 2006;23:579-593. Additional Recommendations Individualized Medical Nutrition Therapy Exercise Aspirin (75-325 mg/d) Smoking cessation Screening for microvascular complications (eyes, kidneys, feet) Immunization ( Flu vaccine, Pneumovax) Recommended cancer screening Optimal Care of the Diabetic Patient Intensive glycemic control Aggressive Rx for CV risk reduction Lifestyle interventions • HbA1c <7% • Dyslipidemia: Statin • Proper nutrition • Glucose (mg/dL): Preprandial 90–130 Postprandial <180 • Hypertension: ≥2 drug classes, include ACEI or ARB • Physical activity program • Microalbuminuria: ACEI or ARB • Smoking cessation • Use of aspirin • CHD: ACEI, -blocker • CVD/high risk: ACEI ADA. Diabetes Care. 2005;28(suppl 1):S1-79. • Weight control Thank You For Your Attention