METFORMIN IMPROVES BLOOD LIPID PATTERN IN NONDIABETIC PATIENTS WITH CORONARY HEART-DISEASE

Objectives. To study whether the addition of metformin further improve s the blood lipid pattern in non-diabetic patients with coronary heart disease already treated with lovastatin, diet and lifestyle advice. D esign. An open, prospective, randomized study in a university hospital setting. Subjects. Sixty non-diabetic male patients previously treate d with coronary artery bypass surgery or angioplasty and with serum ch olesterol greater than or equal to 6.0 mmol L(-1) and/or HDL-cholester ol less than or equal to 1.2 mmol L(-1). Interventions. After a 4-week run-in period with lovastatin (40 mg day(-1)), and diet and lifestyle advice, patients were randomized into two groups, both continuing the run in treatment. One group received metformin up to 2000 mg day(-1); the control group got no additional treatment. Main outcome measures. Fasting serum lipids, glucose and weight were registered at entrance (= week -4), and at weeks 0, 4 and 12. Changes from week 0 to week 4 a nd from week 0 to week 12 were compared. Side-effects of the treatment were also registered. Results. Metformin lowered the LDL/HDL-choleste rol ratio by 12 and 6% at weeks 4 and 12, respectively, and reduced bo dy weight by 1.8 kg at week 12. There was also a transient lowering ef fect on LDL-cholesterol and apolipoprotein B. In the normal weight sub group of patients (body mass index < 27 kg m(-2)), metformin induced a decrease in total cholesterol (-9%), LDL-cholesterol (-12%), LDL/HDL- cholesterol ratio (-10%) and apolipoprotein B (-7%), as compared to th e control group. In this subgroup, body weight and fasting glucose wer e unaffected by metformin. Thus, the lipid lowering effect in normal w eight patients was not secondary to changes in body weight or fasting glucose. In overweight patients (body mass index > 27 kg m(-2)), metfo rmin had no significant effects on blood lipids, but induced a weight loss of -3.0 kg and a transient reduction of fasting glucose. No side- effects were registered apart from those expected from each individual drug. Conclusions. Metformin given for 12 weeks as a supplement to lo vastatin, diet and lifestyle advice to non-diabetic male patients with coronary heart disease further improves the lipid pattern in normal w eight patients, and reduces weight in the overweight patients. Because metformin is cheap and other lipid lowering drugs are expensive, the potential of metformin as a lipid lowering agent should be further inv estigated.