Results of the ACCORD Glycemia Trial on Mortality and the Primary Outcomes Presented at the American Diabetes Association 68th Scientific Sessions on June 10, 2008.

Participant Followup Randomized N=10,251 Intensive Group (N=5128) Refused Intensive Approach (N=11) Lost to Follow-up (N=26) Discontinued Intervention (N=336) Analyzed (N=5128) Excluded from analysis (N=0) Standard Group (N=2123) Refused Standard Approach (N=26) Lost to Follow-up (N=24) Discontinued Intervention (N=322) Analyzed (N=5123)

Median A1C and Interquartile Ranges

Adverse Events Intensive N (%) Standard P CHF 152 (3.0) 124 (2.4) 0.10 MVA* 9 (0.2) 14 (0.3) 0.31 Non-hypo SAE 113 (2.2) 82 (1.6) 0.03 Fluid Retention 3541 (70.1) 3378 (66.8) <0.001 ALT > 3 X Normal 51 (1.0) 77 (1.5) 0.02 *Motor Vehicle Accident

Stopping the Glycemia Comparison 10 member DSMB reviewed interim results every 6 mo. Monitored primary outcome, mortality rates and other variables to assure safety of participants Recommended discontinuing the intensive glycemia intervention on January 8, 2008 after reviewing mortality trends for several months; this was accepted by NHLBI ACCORD participants were informed on February 5 and switched to standard glycemia group goals Results presented here are based on data available to the DSMB at their meeting in January

All Cause Mortality 1.41%/yr 1.14%/yr HR = 1.22 (1.01-1.46) P = 0.04

Primary & Secondary Outcomes Intensive N (%) Standard HR (95% CI) P Primary 352 (6.86) 371 (7.23) 0.90 (0.78-1.04) 0.16 Secondary Mortality 257 (5.01) 203 (3.96) 1.22 (1.01-1.46) 0.04 Nonfatal MI 186 (3.63) 235 (4.59) 0.76 (0.62-0.92) 0.004 Nonfatal Stroke 67 (1.31) 61 (1.19) 1.06 (0.75-1.50) 0.74 CVD Death 135 (2.63) 94 (1.83) 1.35 (1.04-1.76) 0.02 CHF 152 (2.96) 124 (2.42) 1.18 (0.93-1.49) 0.17

Cause of Death Intensive N (%) Standard Unexpected/Presumed CVD 86 (1.7) 67 (1.3) MI 19 (0.4) 13 (0.3) CHF 23 (0.5) 16 (0.3) CV Procedure 10 (0.2) 3 (0.1) Arrhythmia 4 (0.1) Non-CV Procedure 1 (0.02) Stroke 9 (0.2) 11 (0.2) Other CVD 8 (0.2)

Cause of Death, continued Intensive N (%) Standard Cancer 65 (1.3) 63 (1.2) Not Cancer or CVD 50 (1.0) 35 (0.7) Respiratory (not pneumonia) 12 1 Infectious 19 17 Accident/Trauma 8 9 Renal Failure 2 Liver Disease 5 Neurologic 3 Other 4 Indeterminate 7 (0.1) 11 (0.2)

All Cause Mortality 1.41%/yr 1.14%/yr HR = 1.22 (1.01-1.46) P = 0.04

Hazard Ratios for Total Mortality by Subgroup

Primary & Secondary Outcomes Intensive N (%) Standard HR (95% CI) P Primary 352 (6.86) 371 (7.23) 0.90 (0.78-1.04) 0.16 Secondary Mortality 257 (5.01) 203 (3.96) 1.22 (1.01-1.46) 0.04 Nonfatal MI 186 (3.63) 235 (4.59) 0.76 (0.62-0.92) 0.004 Nonfatal Stroke 67 (1.31) 61 (1.19) 1.06 (0.75-1.50) 0.74 CVD Death 135 (2.63) 94 (1.83) 1.35 (1.04-1.76) 0.02 CHF 152 (2.96) 124 (2.42) 1.18 (0.93-1.49) 0.17

Primary Outcome 2.29%/yr 2.11%/yr HR = 0.90(0.78-1.04) P = 0.16

Hazard Ratios for Primary Outcome by Subgroup

Conclusions In people with type 2 diabetes at high risk for CVD, with an A1C of 7.5% or more, a therapeutic strategy that targets an A1C <6% vs. 7.0-7.9% increases mortality over 3.5 years There is no significant effect of the glycemic intervention on the primary outcome at this time Ongoing follow-up and ongoing analyses (both epidemiologic & within baseline subgroups) will add further insight and generate more hypotheses