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Diabetes REduction Assessment with ramipril and rosiglitazone Medication DREAM trial

Worldwide prevalence of diabetes expected to increase . Diabetes prevalence ~171 million in 2000 ~366 million in 2030. World Health Organization, 2000 vs 2030. World Health Organization. www.who.org.. . . . . . . . . . . . . . . . . . . 0. 20. 40. 60. 80. 100. 120. 140. Africa. Americas

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Diabetes REduction Assessment with ramipril and rosiglitazone Medication DREAM trial

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    1. Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial

    3. DECODE: IGT increases mortality risk

    4. DPP: Benefit of diet + exercise or metformin on diabetes prevention in at-risk patients

    5. TZDs: Focus on PPAR? activation Reduces insulin resistance Preserves pancreatic ß-cell function Improves CV risk profile Improves dyslipidemia (?HDL, ?LDL density, ? or ? TG) ?Renal microalbumin excretion ?Blood pressure ?VSMC proliferation/migration in arterial wall ?PAI-1 levels ?C-reactive protein levels ?Adiponectin ?Free fatty acids

    6. TRIPOD: Treating insulin resistance reduces incidence of type 2 diabetes

    7. TZDs blunt diabetes progression

    8. Potential antidiabetic mechanisms of ACE inhibition

    9. HOPE, EUROPA, PEACE: Reduction in new-onset diabetes (placebo-controlled trials)

    10. DREAM: Study design

    11. DREAM: 2 × 2 factorial design

    12. DREAM: Baseline characteristics

    13. DREAM: Rosiglitazone effect on primary outcome

    14. DREAM: Rosiglitazone decreases new-onset diabetes or death

    15. DREAM: Effect of rosiglitazone on primary outcome in key subgroups

    16. DREAM: Conversion to normoglycemia with rosiglitazone

    17. Rosiglitazone effect on weight and BMI

    18. Rosiglitazone effect on waist and hip measurements

    19. DREAM: Ramipril effect on primary outcome

    20. DREAM: Ramipril effects on glycemic categories

    21. DREAM: Safety Rosiglitazone vs placebo Increased incidence of HF* (0.5% vs 0.1%, P = 0.01) No cases of fatal HF No difference for other CV events Increased incidence of peripheral edema (6.8% vs 4.9%, P = 0.003) 4.9-lb weight gain (P < 0.0001) Increased hip circumference (?0.71 in, P < 0.0001) No difference in waist circumference Decreased waist-hip ratio (P < 0.0001) No adverse hepatic effects Alanine aminotransferase (ALT) levels ?4.2 U/L at 1 year (P < 0.0001) Ramipril vs placebo No adverse hepatic effects ALT levels ?1.1 U/L at 1 year (P = 0.004)

    22. DREAM results: Summary Rosiglitazone 60% RRR in new-onset diabetes or death (P < 0.001); NNT = 7 Benefit consistent across ethnicity, gender, and age Increased conversion to normoglycemia* vs placebo (50.5% vs 30.3%) (HR 1.71, P < 0.0001) ?BP vs placebo (1.7/1.4 mm Hg; P < 0.0001) Ramipril 9% RRR in new-onset diabetes or death (P = 0.15) Increased conversion to normoglycemia* vs placebo (42.5% vs 38.2%) (HR 1.16, P = 0.001) ?BP vs placebo (4.3/2.4 mm Hg; P < 0.001) When ACEIs are indicated, improved glucose metabolism may be added benefit

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