Diabetes Trials Unit University of Oxford WebSite: Lipids in Diabetes Study

ldssk01.1 Trial Design Academic, investigator-led, clinical-outcome trial 5,000 type 2 diabetic patients, aged 40 to 75 years “Primary” intervention - no clinical evidence of CHD Double-blind, placebo-controlled, 2x2 factorial randomisation Cerivastatin 0.4 mg/day, micronised fenofibrate 200 mg/day 30 UK clinical centres, five year follow-up Funded by an educational grant from Bayer

ldssk01.2 Exclusion Criteria Thought to require lipid-lowering therapy LDL cholesterol >4.1 mmol/L (160 mg/dL) Triglyceride >4.5 mmol/L (400 mg/dL) Impaired renal/hepatic function History of myopathy or cholelithiasis Life threatening disease Pregnancy

ldssk01.3 Subject Characteristics at Entry n=1616 (May 2000) Mean SD Male67%… Caucasian90%… Current smoker14%… Age (y)608 BMI (kg/m 2 ) Blood pressure (mm Hg)144/8319/11 Duration of diabetes (y)*84 to 13 * Median, IQR

ldssk01.4 Baseline Biochemistry n=1616 (May 2000) Mean SD Total cholesterol (mmol/L) HDL cholesterol (mmol/L) LDL cholesterol (mmol/L) Triglyceride (mmol/L)* to 2.6 HbA 1c (%)* to 9.4 * Median, IQR

ldssk01.5 n=1616 (May 2000) Mean SD Total cholesterol (mg/dL)19531 HDL cholesterol (mg/dL)4712 LDL cholesterol (mg/dL)12127 Triglyceride (mg/dL)*13380 to 231 HbA 1c (%)* to 9.4 Baseline Biochemistry * Median, IQR

ldssk x 2 Factorial Randomisation CerivastatinPlacebo 2,500 Fenofibrate Fenofibrate Fenofibrate(1250) Cerivastatin Placebo 2,500 Placebo Placebo Placebo(1250) 2,5002,5005,000 Cerivastatin Placebopatients in total Cerivastatin arm Fenofibrate arm

ldssk01.7 Composite Primary Endpoint Fatal myocardial infarction including sudden death or Non-fatal myocardial infarction or Coronary or peripheral artery revascularisation First occurrence of:

ldssk01.8 Secondary Outcomes Fatal or non-fatal stroke Coronary syndromes (fatal or non-fatal myocardial infarction, stable and unstable angina) Heart failure All cause mortality Retinal photocoagulation Renal failure

ldssk01.9 Surrogate Outcomes Microalbuminuria Digital electrocardiographic changes Visual acuity Lipid profile

ldssk01.10 Health Economics Four monthly assessment of: Time off work Concomitant drug treatment Hospital admissions/procedures Health resource utilisation EuroQoL-5 (SF-36 at entry & at 5 years)

ldssk01.11 Power of the Study Allocated AllocatedPower at cerivastatinplacebo2p<0.01 * Number randomised2,5002,500… Number evaluable (96%)2,4002,400… LDS primary endpoint % * assuming a 30% reduction in events with cerivastatin and adjusting for factorial design

ldssk01.12 Schedule Study commenced1999 Two year recruitment until2001 Four monthly follow up of all subjects for five years Closeout and publication in2006

ldssk01.13 Conclusions The LDS will demonstrate whether lipid lowering drug therapy reduces cardiovascular events among type 2 patients, many of whom would not be treated on the basis of the current Joint European Recommendations The LDS will provide an evidence-base for the use of statin therapy, fibrate therapy, and combination therapy, for the primary prevention of cardiovascular disease in people with type 2 diabetes