In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m² and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

Fetuses of mothers with gestational diabetes mellitus are at increased risk to develop perinatal complications mainly due to macrosomia. However, in view of the marked heterogeneity of this disease, it seems difficult to set guidelines for diagnosis and treatment. This complicates the choice of assigning patients either to diet or to insulin therapy. Also of concern is how much benefit could be expected from insulin therapy in preventing fetal complications in these patients. In a systematic review of the literature assessing the efficacy of insulin in preventing macrosomia in fetuses of mothers with gestational diabetes, we found six randomized controlled trials comparing diet alone to diet plus insulin. The studies included a total of 1281 patients (644 in the diet plus insulin group and 637 in the diet group), with marked differences among trials concerning diagnostic criteria, randomization process and treatment goals. Meta-analysis of the data resulted in a risk difference of -0.098 (95%CI: -0.168 to -0.028), and a number-necessary-to-treat of 11 (95%CI: 6 to 36), which means that it is necessary to treat 11 patients with insulin to prevent one case of macrosomia. This indicates a potential benefit of insulin, but not significantly enough to set treatment guidelines. Because of the heterogeneous evidence available in the literature about this matter, we conclude that larger trials addressing the efficacy of these two therapeutic modalities in preventing macrosomia are warranted.