1 / 22

D iabetes RE duction A ssessment with ramipril and rosiglitazone M edication (DREAM) trial

D iabetes RE duction A ssessment with ramipril and rosiglitazone M edication (DREAM) trial. Worldwide prevalence of diabetes expected to increase. World Health Organization, 2000 vs 2030. Diabetes prevalence ~171 million in 2000 ~ 366 million in 2030. 140.  155%. 120. 100.  99%.

scott-durham
Download Presentation

D iabetes RE duction A ssessment with ramipril and rosiglitazone M edication (DREAM) trial

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

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

  2. Worldwide prevalence of diabetes expected to increase World Health Organization, 2000 vs 2030 Diabetes prevalence ~171 million in 2000 ~366 million in 2030 140 155% 120 100 99% 102% Diabetes prevalence (in millions) 80 44% 180% 60 40 160% 20 0 W Pacific Africa Americas E Medit Europe SE Asia 2000 2030 World Health Organization. www.who.org.

  3. DECODE: IGT increases mortality risk Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in EuropeN = 25,364 aged ≥30 years Diagnosed diabetes (n = 1275) Undiagnosed diabetes (n = 3071) Impaired glucose tolerance (n = 2766)* Normal glucose tolerance (n = 18,252)* 20 Cumulative mortality hazard (%) 10 0 0 2 4 6 8 10 Follow-up (years) *2-hour oral glucose tolerance test (OGTT) IGT = impaired glucose tolerance DECODE Study Group. Lancet. 1999;354:617-21.

  4. DPP: Benefit of diet + exercise or metformin on diabetes prevention in at-risk patients N = 3234 with IFG and IGT, without diabetes 40 Placebo P* 30 Metformin <0.001 31% Cumulative incidence of diabetes (%) 20 Lifestyle 58% <0.001 10 0 0 1.0 2.0 3.0 4.0 Years *vs placebo IFG = impaired fasting glucose Diabetes Prevention Program (DPP) Research Group. N Engl J Med. 2002;346:393-403.

  5. TZDs: Focus on PPAR activation • Reduces insulin resistance • Preserves pancreatic β-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 Inzucchi SE. JAMA. 2002;287:360-72.

  6. TRIPOD: Treating insulin resistance reduces incidence of type 2 diabetes 12.1% 5.4% TRoglitazone In Prevention Of DiabetesN = 236 Hispanic women with gestational diabetes Annual incidence 60 55% RRR HR 0.45 (0.25–0.83)*P = 0.009 Cumulative incidence of new-onset diabetes (%) 40 Placebo 20 Troglitazone 400 mg 0 0 12 24 36 48 60 Follow-up (months) *Unadjusted Buchanan TA et al. Diabetes. 2002;51:2796-803.

  7. TZDs blunt diabetes progression N = 2343 at high risk of diabetes 15 Placebo Metformin 850 mg bid Cumulative incidence of diabetes (%) 10 Lifestyle Troglitazone400 mg/d* 5 0 0 0.5 1.0 1.5 Follow-up (years) 1568 n = 2343 237 739 DPP Research Group.Diabetes. 2005;54:1150-6. *Withdrawn from study after 1.5 years

  8. Potential antidiabetic mechanisms of ACE inhibition Angiotension I Bradykinin ACE/Kininase II Angiotension II Degradation products ACE Inhibitor Angiotension II Bradykinin Nitric oxide Skeletal muscle blood flow Glucose metabolism Henriksen EJ et al. J Cell Physiol. 2003;196:171-9.

  9. HOPE, EUROPA, PEACE: Reduction in new-onset diabetes (placebo-controlled trials) n = 23,340 free from diabetes* at baseline Overall 14% RRR HR 0.86 (0.78–0.95) P = 0.0023 Ramipril 10 mg Perindopril 8 mg Trandolapril 4 mg (all trials) *Not a prespecified end point Dagenais GR et al. Lancet. 2006;368:581-8.

  10. DREAM: Study design Randomized, double-blind 2 × 2 factorial designN = 5269 with IFG and/or IGT, free from CV disease Ramipril 15 mg/d vs placebo AND Rosiglitazone 8 mg/d vs placebo Primary outcome:Diabetes or death from any cause Secondary outcomes I: CV eventsCombined MI, stroke, CV death, revascularization, HF, angina, ventricular arrhythmia Secondary outcomesII: Renal eventsProgression to micro- or macroalbuminuria, or 30% CrCl Secondary outcomesIII: Glucose status Glucose levels,conversion to normoglycemia Follow-up: 3–5 years DREAM Trial Investigators. Diabetologia. 2004;47:1519-27.

  11. DREAM: 2 × 2 factorial design N = 5269 with IFG and/or IGT Rosiglitazone Placebo Ramipril Ramipril + Rosiglitazone Ramipril + Placebo Placebo Rosiglitazone + Placebo Placebo + Placebo Ramipril: 5 mg × 2 months; 10 mg × 10 months; 15 mg thereafter Rosiglitazone: 4 mg × 2 months; 8 mg thereafter DREAM Trial Investigators. Diabetologia. 2004;47:1519-27.

  12. DREAM: Baseline characteristics Age (years) 54.7 (±10.9) Women (%) 58.5 Hypertension (%) 43.5 Hyperlipidemia (%) 35.5 BP (mm Hg) 136/83 (±18.6/11.3) BMI (kg/m2) 30.5 (±5.1) Waist circumference (inches) Men 34.3 (±10.8) Women 32.6 (±11.9) Glucose FPG (mg/dL) 104 (±12.6) IFG (%) 42.4 2-hour (mg/dL) 157 (±25.2) IGT (%) 85.9 DREAM Trial Investigators. Diabetologia. 2004;47:1519-27.

  13. DREAM: Rosiglitazone effect on primary outcome 0.6 Placebo 60% RRR HR 0.40 (0.35–0.46) P < 0.0001 0.5 0.4 Cumulative hazard rate 0.3 0.2 Rosiglitazone 0.1 0.0 0 1 2 3 4 Follow-up (years) No. at riskPlaceboRosiglitazone 26342635 24702538 21502414 11481310 177217 DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

  14. DREAM: Rosiglitazone decreases new-onset diabetes or death N = 5269 Favorsrosiglitazone Favorsplacebo P <0.0001 <0.0001 0.70 0.25 1 1.75 Hazard ratio *Participants may appear in both categories DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

  15. DREAM: Effect of rosiglitazone on primary outcome in key subgroups P* Placebo (% per year) Favors rosiglitazone Favors placebo Gender Male Female Age (years) <50 60+ 50–59 Location North America South America Europe India Australia Glycemic abnormality IFG only IGT only IFG + IGT 9.9 7.6 8.4 9.5 7.7 8.8 8.0 8.6 8.7 7.2 7.0 6.1 14.0 0.6 0.09 0.09 0.14 0.2 0.4 0.6 0.8 1.0 1.2 Hazard ratio (95% CI) *for heterogeneity DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

  16. DREAM: Conversion to normoglycemia with rosiglitazone N = 5269 71% increaseHR 1.71 (1.571.87)P < 0.0001 *FPG < 110 mg/dL and 2-h glucose < 140 mg/dL DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

  17. Rosiglitazone effect on weight and BMI Weight BMI 200 32 196 31 191 lbs kg/m2 187 30 P < 0.0001 P < 0.0001 182 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Follow-up (years) Rosiglitazone Placebo DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

  18. Rosiglitazone effect on waist and hip measurements WHR Circumference 45.3 0.94 Hip 43.7 0.92 42.1 P < 0.0001 inches 40.6 Waist 0.90 P < 0.0001 39.0 P = NS 37.4 0.88 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Follow-up (years) Rosiglitazone Placebo WHR = waist-hip ratio DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

  19. DREAM: Ramipril effect on primary outcome 0.6 9% RRRHR 0.91 (0.81–1.03) P = 0.15 0.5 Placebo 0.4 Cumulative hazard rate 0.3 0.2 Ramipril 0.1 0.0 0 1 2 3 4 Follow-up (years) 26462623 25102498 22772287 12401218 200194 No. at riskPlaceboRamipril DREAM Trial Investigators. N Engl J Med. 2006;355:1551-62.

  20. DREAM: Ramipril effects on glycemic categories P = 0.006 DREAM Trial Investigators. N Engl J Med. 2006;355:1551-62.

  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) DREAM Trial Investigators. Lancet. 2006;368:1096-1105; N Engl J Med. 2006;355:1551-62. *Adjudicated

  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 DREAM Trial Investigators. Lancet. 2006;368:1096-1105;N Engl J Med. 2006;355:1551-62. *FPG < 110 mg/dL and 2-h glucose < 140 mg/dL

More Related