SIMVASTATIN IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS - EFFECT ON SERUM-LIPIDS, LIPOPROTEINS AND HEMOSTATIC MEASURES

The clinical efficacy of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitor simvastatin in the treatment of hypercholesterolaemia in non-insulin-dependent diabetes (NIDDM), was examined in a double-blind placebo-controlled study of 6 months in 70 patients with NIDDM (age 25-70 years), of whom 57 were randomised to placebo (29 patients) or simvastatin for 6 months, following a 3-month run-in on diet. Patients were hypercholesterolaemic (7.8 (7.6-8.0) (mean (95% confidence intervals)) mmol/l simvastatin vs. 8.0 (7.7-8.5) mmol/l placebo) and mildly hypertriglyceridaemic (2.6 (2.2-3.0) simvastatin vs. 2.9 (2.3-3.5) placebo). Other lipid measures and estimates of glycaemic control and haemostasis were similar in both groups. There were no significant changes in lipids, haemostatic factors, or measures of glycaemic control in the placebo treatment group. Conversely by the end of 24 weeks, simvastatin produced a 28% reduction in cholesterol (to 5.6 (5.0-6.2) mmol/l (P < 0.001)), a 38% reduction in LDL cholesterol (from 5.5 (5.4-5.6) mmol/l to 3.4 (2.8-4.0) mmol/l, P < 0.001), a 15% reduction in triglyceride (to 2.2 (1.8-2.6) mmol/l, P < 0.05, and a 9% rise in HDL (from 1.16 (1.07-1.25) to 1.23 (1.14-1.32) mmol/l, P < 0.05). Improvements in apolipoprotein B (ape B) (-28%, P < 0.001), the LDL cholesterol to apo B ratio (-20%, P < 0.001), and apo Al (+15%, P < 0.001) were recorded. There were no effects upon fibrinogen, factor VII activity, factor VIII activity, or measures of glycaemic control (fasting glucose, insulin, C-peptide, or HbA(1)). Simvastatin is an effective treatment for hypercholesterolaemia in NIDDM with normal or mildly elevated triglycerides, which is well tolerated and has no adverse effect upon glycaemic control. Simvastatin may additionally reduce triglycerides and improve the abnormality of LDL composition which is characteristic of hyperlipidaemic NIDDM.