1 Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators* Lancet, Vol 368 September 23, 2006 R2 이윤정

2 Impaired fasting glucose or impaired glucose tolerance are asymptomatic, high risk of future diabetes and vascular disease Rosiglitazone (thiazolidinedione) : peroxisome proliferator-activated gamma(PPARr) receptors, increases hepatic and peripheral insulin sensitivity, preserves insulin secretion Background

3 Acarbose and metformin reduce incident diabetes by 25–30%; lifestyle interventions that target diet and physical activity reduce incident diabetes by more than 50%, but are difficult to sustain. THE LANCET Vol 359.June15,2002 Background

4 Fasting Plasma Glucose Concentrations (Panel A) Glycosylated Hemoglobin Values (Panel B) According to Study Group. N Engl J Med, Vol. 346, No. 6,February 7, 2002 Background

5 DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial  Assess prospectively whether rosiglitazone can reduce the frequency of diabetes in individuals with impaired glucose tolerance or impaired fasting glucose, or both. Background

6 DREAM trial : people, aged 30 years or more were assessed for eligibility with a 75 g oral glucose tolerance test between July, 2001, and August, 2003, at 191 sites in 21 countries. Inclusion criteria : 1) impaired fasting glucose (fasting plasma glucose concentration ≥6 ・ 1 mmol/L and <7 ・ 0 mmol/L and 2-h plasma glucose concentration <11 ・ 1 mmol/L during the oral glucose tolerance test) 2) impaired glucose tolerance (fasting plasma glucose concentration <7 ・ 0 mmol/L and 2-h plasma glucose concentration ≥7 ・ 8 mmol/L and <11 ・ 1 mmol/L) Exclusion criteria : history of diabetes (except gestational diabetes), cardiovascular disease (including heart failure and known low ejection fraction), or intolerance to either angiotensinconverting enzyme inhibitors or thiazolidinediones Methods

7 Figure 1: Trial profile Data were censored at time of last follow-up for all participants. 4mg once daily for first 2months and then 8mg once daily

8 Primary outcome : incident diabetes or death from any cause during the active treatment period Secondary outcomes : (1) regression to normal fasting and 2-h post-load glucose concentrations, defi ned as a fasting plasma glucose concentration of less than 6 ・ 1 mmol/L and a 2-h plasma glucose concentration of less than 7 ・ 8 mmol/L (2) a composite of cardiovascular events (myocardial infarction, stroke, cardiovascular death, revascularisation procedures, heart failure, new angina with objective evidence of ischaemia, or ventriculararrhythmia needing resuscitation) (3) individual components of this cardiovascular composite (4) renal events and a composite cardiorenal outcome (5) glucose concentrations. Methods

9 RESULT

10 Table 1: Baseline clinical and biochemical characteristics of participants

11 Table 2: Primary and other outcomes

12 Figure 2: Time to occurrence of primary outcome

13 Figure 3: Effect of rosiglitazone on the primary outcome in key subgroups

14 Figure 4: Proportion of participants who either developed diabetes,regressed to normal, or had impaired fasting glucose or impaired glucose tolerance, or both, at the last assessment (A) FPG defi ned as concentration <6 ・ 1 mmol/L or (B) <5 ・ 6 mmol/L.

15 Figure 5: Effect of rosiglitazone on the point estimates of (A) fasting plasma glucose (FPG) and (B) 2-h plasma glucose (PG) concentrations 1.6mmol/L 0.5mmol/L

16 Figure 6: The effect of rosiglitazone on weight and fat distribution 2.2Kg

17 Rosiglitazone significantly increased the likelihood of regression to normoglycemia by about 70–80% compared with placebo. lifestyle approaches and greater than the reductions reported previously with drugs such as metformin or acarbose. Discussion

18 Rosiglitazone : reduce or eliminate the relation between increasing obesity and a higher risk of diabetes 1) Increasing the effectiveness of endogenous insulin. 2) Slow the fall in β-cell function with time by reducing the physiological demand for basal as well as prandial insulin secretion (ie, through insulin sensitisation) or by a direct β-cell cytoprotective effect 3) Fat accumulation in non-visceral compartments,increased secretion of adiponectin and reduced levels of inflammatory cytokines, and is associated with less diabetes. Discussion

19 Discussion Vasodilation, Increase of insulin-sensitivity, BP decrease CHF Aggravation Na, Water retension Fluid overload Rosiglitazone Heart failure with a thiazolidinedione was about ten times lower in participants at low risk of cardiovascular events in the DREAM trial than in a cardiovascular prevention trial of participants at high risk  Reduced susceptibility of lower risk people to heart failure.

20 Rosiglitazone at 8 mg daily for 3 year (DREAM trial)  Reduces incident type 2 diabetes  Increases the likelihood of regression to normoglycemia in adults with impaired fasting glucose or impaired glucose tolerance, or both Conclusion