1. Therapy of Type 2 Diabetes Mellitus: UPDATE Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines: Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM) Stan Schwartz MD, FACP, FACE Affiliate, Main Line Health System Clinical Associate Professor of Medicine, Emeritus, U of Pa. stschwar@gmail.com Part 2

2. Early Treatment Decreases Micro and Macro Vascular RISK

3. Impact of Intensive Therapy in Type 2 Diabetes Summary of Major Clinical Trials: BUT Subset Evaluations Show Reduced CV Outcomes if shorter duration of DM, without significant pre-existing complications Initial Trial Long Term Follow-up ↑- likely due to hypoglycemia and weight gain

4. Lancet Meta-analysis 0.9% Dec. HbA1c, 17% Dec. non-fatal MI, 15% Dec. CV events of CAD Probability of events of non-fatal MI with intensive glucose-lowering vs. standard treatment 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Intensive treatment better Standard treatment better Probability of events of CAD with intensive glucose-lowering vs. standard treatment 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Intensive treatment better Standard treatment better www.thelancet.com. Vol 373 May 23, 2009. *Included on-fatal MI and death from all-cardiac mortality

5. But Why was there an apparent increase in Mortality in ACCORD, lack of benefit in ADVANCE, VADT • Weight Gain • Hypoglycemia • ACCORD recorded PRIOR history mild severe events- • NO DOCUMENTATION OF GLUCOSE AT TIME OF DEATH

8. But Why was there an apparent increase in Mortality in ACCORD, lack of benefit in ADVANCE, VADT • Weight Gain • Hypoglycemia • ACCORD recorded PRIOR history mild severe events- • NO DOCUMENTATION OF GLUCOSE AT TIME OF DEATH

10. Hypoglycemia Outcomes VADT, ACCORD, ADVANCE

11. Consequences of Hypoglycemia • Prolonged QT- intervals- Diabetologia 52:42,2009 • Can be of pronged duration IJCP Sup 129, 7/02 • Greater with higher catecholamine levels Europace 10,860 • Associated with Angina Diabetes Care 26, 1485, 2003 / Ischemic EKG changes Porcellati, ADA2010 • Associated with Arrhythmias • Associated with Sudden Death Endocrine Practice 16,¾ 2010 • Increased Variabilty- explains highest mortality in intensive group had highest HgA1c in ACCORD ( increases inflammation, ICU mortality Hirsch ADA2010)

12. VALUE OF CONTROLLING HYPERGLYCEMIA IN HOSPITAL RISK OF TOO TIGHT CONTROL OF HYPERGLYCEMIA IN HOSPITALS

13. So given epidemiologic data, CV risk/glucose data and now ADVANCE, VADT, ACCORD, implications of weight gain and hypogycemia, what are/ should be goals (SSS) 1. ADA- stayed at <7.0 AACE – stayed at < 6.5 Lowest possible as long as no undue risk of hypoglycemia and visceral weight gain 2. ADA and AACE- • Start early in DM - implications for prevention- lifestyle and drug therapy of metabolic syndrome and IGT b. do not aim for aggressive control in those with significant pre-existing CV disease Disagree- lowest possible without hypoglycemia, weight gain • Modify goals for ‘elderly’ Disagree- lowest possible without hypoglycemia, weight gain

14. Greater Survival in Elderly (>75yo) with lower HgA1c So… WHY NOT BE AGGRESSIVE IN GLYCEMIC CONTROL IF… NOT USING HYPOGLYCEMIC AGENTS EASD , 9/2010