1 / 15

ADOPT

ADOPT. A D iabetes O utcome P rogression T rial. ADOPT: Background and rationale. Attaining and maintaining glycemic control reduces risk of long-term diabetes complications Despite initial efficacy with lifestyle + pharmacologic interventions, glycemic control is lost over time

karins
Télécharger la présentation

ADOPT

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. ADOPT ADiabetes Outcome Progression Trial

  2. ADOPT: Background and rationale • Attaining and maintaining glycemic control reduces risk of long-term diabetes complications • Despite initial efficacy with lifestyle + pharmacologic interventions, glycemic control is lost over time • Thiazolidinediones reduce insulin resistance, delay progression to T2DM, and have been reported to preserve β-cell function ADOPT was designed to evaluate glycemic control in recently diagnosed T2DM patients receiving monotherapy with rosiglitazone, metformin, or glyburide T2DM = type 2 diabetes mellitus Viberti G et al. Diabetes Care. 2002;25:1737-43.

  3. ADOPT: Study design Primary endpoint: Time to monotherapy failure (FPG >180 mg/dL) Screening Run-in period (4 weeks) Treatment period (4 years) Placebo + Diet/exercise Rosiglitazone4–8 mg/day* Metformin0.5–2 g/day* Glyburide2.5–15 mg/day* • Eligible patients: • T2DM diagnosed within 3 years • No prior oral hypoglycemic agents or insulin therapy • FPG: 126–240 mg/dL Non-treatment observational follow-up N = 6676 Randomization baseline (visit 3) N = 4360 Failure of monotherapy action point Study end *Uptitrate when fasting plasma glucose (FPG) ≥140 mg/dL at subsequent visits Viberti G et al. Diabetes Care. 2002;25:1737-43.Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  4. ADOPT: Patient enrollment and outcomes RandomizedN = 4360 Rosiglitazonen = 1456 Metforminn = 1454 Glyburiden = 1441 Completed trialn = 917 Completed trialn = 903 Completed trialn = 807 No significant treatment group differences in patient characteristics in those who withdrew from study Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  5. ADOPT: Baseline characteristics Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  6. ADOPT: Baseline BP, glucose, and lipid values *Homeostasis model assessment (HOMA 2) Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  7. ADOPT: Treatment effect on primary outcome N = 4351 40 Hazard ratio (95% CI) Rosiglitazone vs metformin, 0.68 (0.55–0.85), P < 0.001 Rosiglitazone vs glyburide, 0.37 (0.30–0.45), P < 0.001 Glyburide 30 Cumulative incidence of mono-therapy failure*(%) Metformin 20 Rosiglitazone 10 0 0 1 2 3 4 5 Years *Time to FPG >180mg/dL Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  8. ADOPT: Treatment effect on glucose control Treatment difference* (95% CI) Rosiglitazone vs metformin -9.8 (-12.7 to -7.0), P < 0.001 Rosiglitazone vs glyburide -17.4 (-20.4 to -14.5), P < 0.001 Treatment difference* (95% CI) Rosiglitazone vs metformin -0.13 (-0.22 to -0.05), P = 0.002 Rosiglitazone vs glyburide -0.42 (-0.50 to -0.33), P < 0.001 8.0 160 7.6 150 7.2 140 FPG (mg/dL) A1C(%) 6.8 130 6.4 120 6.0 110 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Years Years Rosiglitazone Metformin Glyburide *At 4 years Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  9. ADOPT: Treatment effect on insulin sensitivity and β-cell function 70 100 Treatment difference* (95% CI) Rosiglitazone vs metformin 12.6 (8.1 to 17.3), P < 0.001 Rosiglitazone vs glyburide 41.2 (35.2 to 47.4), P < 0.001 Treatment difference* (95% CI) Rosiglitazone vs metformin 5.8 (1.9 to 9.8), P = 0.003 Rosiglitazone vs glyburide -0.8 (-4.7 to 3.1), P = 0.67 60 90 50 80 -Cell Insulin sensitivity†(%) function† (%) 40 70 30 60 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Years Years Rosiglitazone Metformin Glyburide *At 4 years †Homeostasis model assessment (HOMA 2) Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  10. ADOPT: Treatment effect on weight and waist circumference Treatment difference* (95% CI) Rosiglitazone vs metformin 6.9 (6.3 to 7.4), P < 0.001 Rosiglitazone vs glyburide 2.5 (2.0 to 3.1), P < 0.001 Treatment difference* (95% CI) Rosiglitazone vs metformin 4.11 (3.18 to 5.04), P < 0.001 Rosiglitazone vs glyburide 0.77 (-0.21 to 1.76), P = 0.12 218 42.9 213 209 42.1 Waistcircum-ference(in) 204 Weight (lbs) 200 41.3 196 191 40.6 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Years Y ea r s Rosiglitazone Metformin Glyburide *At 4 years Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  11. ADOPT: Treatment effect on hip circumference and waist/hip ratio Treatment difference* (95% CI) Rosiglitazone vs metformin 5.31 (4.39 to 6.33), P < 0.001 Rosiglitazone vs glyburide 2.42 (1.44 to 3.39), P < 0.001 Treatment difference* (95% CI) Rosiglitazone vs metformin -0.0083 (-0.0158 to -0.0009), P = 0.03 Rosiglitazone vs glyburide -0.0107 (-0.0186 to -0.0028), P = 0.008 45.3 0.96 44.5 Hipcircum-ference(in) Waist/hipratio 0.95 43.7 0.94 42.9 0 0 0 1 2 3 4 5 0 1 2 3 4 5 Years Years Rosiglitazone Metformin Glyburide *At 4 years Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  12. ADOPT: Adverse events *Investigator reported; †Self reported Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  13. ADOPT: Fracture event rate Not part of prespecified analysis Note added in proof *P < 0.01 vs rosiglitazone; †P < 0.05 vs rosiglitazone Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  14. ADOPT: Summary • Compared with metformin and glyburide, initial treatment of T2DM with rosiglitazone over 4 years demonstrated clinical benefits: • Slowed progression to monotherapy failure (loss of glycemic control) • Improved insulin sensitivity and reduced -cell function loss • Rosiglitazone associated with: • More weight gain and edema than metformin or glyburide • Fewer GI events than metformin • Less hypoglycemia than glyburide • Similar risk of CV events vs metformin • Higher risk of CV events than glyburide Kahn SE et al. N Engl J Med. 2006;355:2427-43.

  15. ADOPT: Implications • ADOPT provides long-term data on the glycemic durability and risks associated with rosiglitazone, metformin, and glyburide in the management of T2DM • Risk/benefit ratios should be considered when guiding optimal therapy in high-risk patients Kahn SE et al. N Engl J Med. 2006;355:2427-43.

More Related