1. Diabetes Update Division of Endocrinology Department of Medicine Wayne State University Medical School Detroit, Michigan Part 1 of 3

2. Diabetic Retinopathy Leading cause of blindness in adults Diabetic Nephropathy Major cause of kidney failure Cardiovascular Disease Stroke Diabetic Neuropathy 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.

3. 3 42% Of Diabetes Costs Related To Hospitalization And Long-Term Care $200 Billion Total! 2010 US Total Healthcare Costs Attributable To Diabetes 50 40 30 20 10 0 Direct Costs Indirect Costs ‡ Oral Antidiabetics Insulin and Supplies Outpatient Medication* Outpatient Services † Physician Office Visits Nursing Home Care (11%) Inpatient Care (31%)

4. ADA and AACE/ACE Guidelines: Treatment Goals for A1C, FPG, and PPG Parameter Normal 1,2 Level ADA 3 Goal AACE/ACE 2 Goal FPG, mg/dL<10090–130<110 PPG, mg/dL<140<180<140 A1C, %4–6 <7 a ≤6.5 FPG=fasting plasma glucose; PPG=postprandial glucose; ADA=American Diabetes Association; AACE=American Association of Clinical Endocrinologists; ACE=American College of Endocrinology. 1. Adapted from Buse J et al. In: Williams Textbook of Endocrinology. 10th ed. 2003. Permission requested. 2. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13:(suppl 1)3–68. 3. ADA. Diabetes Care. 2007;30:S4–S41. a The goal for an individual patient is to achieve an A1C as close to normal (<6%) as possible without significant hypoglycemia.

5. 5 Components of HbA1c HbA1c = FBS + PPBS

6. 6 Both Fasting and Postprandial Hyperglycemia Contribute to A1C Plasma Glucose (mg/dL) Adapted from Riddle MC. Diabetes Care. 1990;13:676-686 300 200 100 0 Time of Day 6 AM12 PM6 PM12 AM6 AM Normal glycemic exposure A1C ~5% Uncontrolled Diabetes With A1C ~8% Postprandial Hyperglycemia Fasting Hyperglycemia

7. Normal Physiology DEMAND SUPPLY

8. Hyperglycemia

9. 9 Type 2 Diabetes Is a Complex and Progressive Metabolic Disorder 1. Kendall DM, et al. International Diabetes Center. 2005. 2. DeFronzo DA. Diabetes. 2009. 3. Fehse F, et al. J Clin Endocrinol Metab. 2005. Adapted from Kendall DM, Bergenstal RM. History and Progression of Type 2 Diabetes 1-3 By the time of diabetes onset, up to 80% of beta-cell function may be lost 2,3 Diagnosis

10. 10 Unmet Needs for Type 2 DM Treatment Durable HbA 1c control (i.e. help improve Beta-cell function). Addressing islet dysfunction (i.e., addressing both insulin and glucagon secretion. Addressing both fasting and postprandial sugars Minimum risk of treatment-limiting adverse events: -Minimum risk of hypoglycemia -Minimum risk of weight gain -No increased risk of edema -No increased risk of heart failure