1. Journal Club 亀田メディカルセンター 糖尿病内分泌内科 Diabetes and Endocrine Department, Kameda Medical Center 松田 昌文 Matsuda, Masafumi 2007 年 11 月 1 日 8:20-8:50 B 棟８階 カンファレンス室

2. 2 Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279 LaRosa JC et al. N Engl J Med 2005;352:1425-1435 LDL-C achieved mg/dL (mmol/L) WOSCOPS – Placebo AFCAPS - Placebo ASCOT - Placebo AFCAPS - RxWOSCOPS - Rx ASCOT - Rx 4S - Rx HPS - Placebo LIPID - Rx 4S - Placebo CARE - Rx LIPID - Placebo CARE - Placebo HPS - Rx 0 5 10 15 20 25 30 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) Event rate (%) 6 Secondary Prevention Primary Prevention Rx - Statin therapy PRA – pravastatin ATV - atorvastatin 200 (5.2) PROVE-IT - PRA PROVE-IT – ATV TNT – ATV10 TNT – ATV80 LDL-C and Cardiovascular Event Rate

3. Original Article HDL Cholesterol, Very Low Levels of LDL Cholesterol, and Cardiovascular Events Philip Barter, M.D., Ph.D., Antonio M. Gotto, M.D., D.Phil., John C. LaRosa, M.D., Jaman Maroni, M.D., Michael Szarek, M.S., Scott M. Grundy, M.D., Ph.D., John J.P. Kastelein, M.D., Ph.D., Vera Bittner, M.D., M.S.P.H., Jean-Charles Fruchart, Pharm.D., Ph.D., for the Treating to New Targets Investigators N Engl J Med Volume 357(13):1301-1310 September 27, 2007

4. Study Overview In a post hoc analysis of the Treating to New Targets study, high-density lipoprotein cholesterol levels in patients receiving statin therapy were shown to be predictive of subsequent major cardiovascular events, even when low- density lipoprotein (LDL) cholesterol levels were taken into account and even among patients with very low levels of LDL cholesterol (<70 mg per deciliter)

5. Baseline Characteristics of the Patients According to Quintile of HDL Cholesterol Level at Month 3 Barter P et al. N Engl J Med 2007;357:1301-1310

6. Multivariate Analysis of the Relationship between HDL Cholesterol Levels at Month 3 and the Risk of Major Cardiovascular Events Barter P et al. N Engl J Med 2007;357:1301-1310

7. Multivariate Analysis of the Relationship between Major Cardiovascular Events and Quintiles of HDL Cholesterol Levels Barter P et al. N Engl J Med 2007;357:1301-1310

8. Relationship between Major Cardiovascular Events and Ratio of LDL Cholesterol to HDL Cholesterol at Month 3 (Panel A) and Ratio of Total Cholesterol to HDL Cholesterol at Month 3 (Panel B) Barter P et al. N Engl J Med 2007;357:1301-1310

9. Relationship between HDL Cholesterol Levels and the Risk of Major Cardiovascular Events Barter P et al. N Engl J Med 2007;357:1301-1310

10. Conclusion In this post hoc analysis, HDL cholesterol levels were predictive of major cardiovascular events in patients treated with statins This relationship was also observed among patients with LDL cholesterol levels below 70 mg per deciliter

12. Original Article Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes Rury R. Holman, M.B., Ch.B., F.R.C.P., Kerensa I. Thorne, M.Sc., Andrew J. Farmer, D.M., F.R.C.G.P., Melanie J. Davies, M.D., F.R.C.P., Joanne F. Keenan, B.A., Sanjoy Paul, Ph.D., Jonathan C. Levy, M.D., F.R.C.P., for the 4-T Study Group N Engl J Med Volume 357(17):1716-1730 October 25, 2007

13. Study Overview In an open-label trial, patients with type 2 diabetes with a suboptimal glycated hemoglobin level while receiving a maximally tolerated dose of metformin and sulfonylurea were randomly assigned to receive biphasic, prandial, or basal insulin The addition of a single analogue-insulin formulation resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. Regimens of biphasic or prandial insulin had greater efficacy than did the basal regimen but were associated with greater risks of hypoglycemia and weight gain

14. Enrollment and Outcomes Holman RR et al. N Engl J Med 2007;357:1716-1730

15. Characteristics of the Patients at Baseline Holman RR et al. N Engl J Med 2007;357:1716-1730

16. Primary and Secondary Outcomes at 1 Year Holman RR et al. N Engl J Med 2007;357:1716-1730

17. Outcomes and Changes from Baseline at 1 Year Holman RR et al. N Engl J Med 2007;357:1716-1730

18. Mean (±SE) Percentage Change from Baseline to 1 Year in Glycated Hemoglobin, Fasting Plasma Glucose, Postprandial Glucose, and Body Weight (Panel A) and Mean (+SD) Hypoglycemic-Event Rate (Panel B) Holman RR et al. N Engl J Med 2007;357:1716-1730

19. Adverse Events Holman RR et al. N Engl J Med 2007;357:1716-1730

20. Conclusion A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. The addition of biphasic or prandial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain