1. Diabetes Trials Unit University of Oxford WebSite: http://www.dtu.ox.ac.uk/lds Lipids in Diabetes Study

2. 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

3. 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

4. ldssk01.3 Subject Characteristics at Entry n=1616 (May 2000) Mean SD Male67%… Caucasian90%… Current smoker14%… Age (y)608 BMI (kg/m 2 )30.3 6.0 Blood pressure (mm Hg)144/8319/11 Duration of diabetes (y)*84 to 13 * Median, IQR

5. ldssk01.4 Baseline Biochemistry n=1616 (May 2000) Mean SD Total cholesterol (mmol/L)5.00.8 HDL cholesterol (mmol/L)1.20.3 LDL cholesterol (mmol/L)3.10.7 Triglyceride (mmol/L)*1.50.9 to 2.6 HbA 1c (%)*8.37.3 to 9.4 * Median, IQR

6. 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 (%)*8.37.3 to 9.4 Baseline Biochemistry * Median, IQR

7. ldssk01.6 2 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

8. 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:

9. 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

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

11. 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)

12. ldssk01.11 Power of the Study Allocated AllocatedPower at cerivastatinplacebo2p<0.01 * Number randomised2,5002,500… Number evaluable (96%)2,4002,400… LDS primary endpoint17925590% * assuming a 30% reduction in events with cerivastatin and adjusting for factorial design

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

14. 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