Glycemia Treatment Strategies Used In ACCORD

1. Glycemia Treatment Strategies Used In ACCORD Presented at the American Diabetes Association 68th Scientific Sessions on June 10, 2008.

2. OUTLINE • Glycemia Levels Achieved in the Intensive and Standard Arms • How Targets Were Achieved • Changes in Body Weight • Severe Hypoglycemia

3. Glycemia Levels Achieved

4. A1C Distribution Standard Rx Goal Intensive Rx Goal

5. A1C Distribution: 12 Mo. Standard Rx Goal Intensive Rx Goal

6. A1C Distribution: 24 Mo. Standard Rx Goal Intensive Rx Goal

7. A1C Distribution: 36 Mo. Standard Rx Goal Intensive Rx Goal

8. A1C Distribution: 48 Mo. Standard Rx Goal Intensive Rx Goal December 2007

9. Median A1C and Interquartile Ranges The mean difference during the trial was 1.1%

10. How Targets Were Achieved

11. Achieving Glycemic Goals * depending on the blood pressure group assignment

12. Achieving Glycemic Goals

13. ACCORD Glycemia Formulary • Metformin • Rosiglitazone • Glimepiride • Repaglinide • Acarbose • Glargine Insulin • Aspart Insulin • 70/30, N, R Insulin • Exenatide

14. Medications Ever Used During the Trial * % of Participants

15. Usage of Insulin at Last Visit

16. Design of Intensive Glycemia Intervention Even if the A1C is <6.0 Rx was reduced in the presence of significant hypoglycemia.

17. Design of Standard Glycemia Intervention **Decrease only insulin or insulin secretagogues.

18. Changes in Body Weight

19. Changes in Body WeightSince Baseline Increase Decrease

20. Severe Hypoglycemia

21. ACCORD Definition of aSevere Hypoglycemic Episode • Hypoglycemia requiring medical or paramedical attention, AND • Documented blood glucose < 50 mg/dl (2.8 mmol/L), or • Prompt recovery with administration of oral CHO, IV glucose, or subcutaneous glucagon Each participant’s ‘Glucose Diary’ was reviewed at each clinic visit to identify the occurrence of one of these hypoglycemic events

22. Severe Hypoglycemia Monitoring & Management • Severe hypoglycemia events monitored and reported by the clinics • Systematic monitoring, review, and feedback used • Monitors within and external to ACCORD • Feedback on management and prevention provided; A1C goal relaxed, as indicated • Multiple events required detailed review and preventative intervention

23. Number of Participants with Severe Hypoglycemia

24. Number of Participants With One or More Severe Hypoglycemia Events Requiring Medical Assistance (n and %) **Cumulative number of events

25. Incidence of Severe Hypoglycemia per Year (1st event) % of Participants Year Post-randomization

26. ConclusionDifferent Glycemia Treatment Strategies Were Used • Compared with the standard group, the intensive group had: • Lower A1C goal (< 6% vs. 7 - 7.9%) • More visits (q 1-2 mo + at least 1 interim call) • Point of care A1C • Greater use of multiple medications • Greater use of insulin

27. ConclusionDifferent Glycemia Treatment Strategies Were Used Implementation of the Intensive Glycemia Strategy versus the Standard Glycemia Strategy was associated with: • More weight gain and in larger number of participants • More frequent episodes of severe hypoglycemia (either single and multiple) in a larger number of participants • Higher rate of mortality