Effects of Simvastatin and Metformin on Inflammation and Insulin Resistance in Individuals with Mild Metabolic Syndrome
In addition to lipid-lowering and insulin-sensitizing actions, statins (HMG-CoA reductase inhibitors) and metformin may have pleiotropic effects.
To study the effect of simvastatin and metformin on insulin sensitivity and inflammatory markers.
Forty-one subjects with body mass index (BMI) 25–39.9 kg/m2 and impaired glucose tolerance were randomized to receive simvastatin or metformin for 16 weeks. Blood samples were obtained for measurement of metabolic and inflammatory parameters before and after each treatment.
As expected, when compared with simvastatin, metformin therapy resulted in significant reductions in mean BMI, fasting plasma glucose, and homeostasis model assessment-insulin resistance (HOMA-IR), whereas simvastatin treatment resulted in significantly reduced total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B levels. Independently of the medication used, significant decreases in C-reactive protein (CRP) and interleukin (IL)-6 were detected from baseline to treatment end. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (p = 0.002) over the 16-week intervention period and IL-6 a mean reduction was 0.35 ± 0.17 pg/mL (p = 0.046). No change was observed in the tumor necrosis factor-α levels. Baseline values of CRP and IL-6 and their percentage declines were correlated (r = 0.71 and r = 0.67, respectively; p < 0.001). In simvastatin recipients, no correlation was detected between reductions in CRP or IL-6 and lipids, whereas in metformin recipients, reductions in inflammatory markers were not correlated to BMI and HOMA-IR. Conclusion: Our findings suggest that both metformin and simvastatin have similar beneficial effects on low-grade inflammation, in addition to their classical effects on glucose and lipid metabolism. Moreover, they confirm the importance of treating at-risk individuals even before the precipitation of overt diabetes mellitus or full-blown metabolic syndrome.
This research was supported by Fundação de Amparo à Pesquisa de Estado de São Paulo (FAPESP) [02/10010-9]. The authors have no conflicts of interest that are directly relevant to the content of this study.
- 12.Grundy SM, Hansen B, Smith Jr SC, et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation 2004; 109: 551–6.PubMedCrossRefGoogle Scholar
- 13.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 2002; 106: 3143–421.Google Scholar
- 14.United Kingdom Prospective Diabetes Study Group: effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65.Google Scholar
- 21.Caballero AE, Delgado A, Aguilar-Salinas CA, et al. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 2004; 89: 3943–8.PubMedCrossRefGoogle Scholar
- 22.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2006; 29 Suppl. 1: S43–8.Google Scholar
- 23.Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice. A statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation 2003; 107: 499–511.PubMedCrossRefGoogle Scholar
- 30.Caballero AE, Delgado A, Aguilar-Salinas CA, et al. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab 2004; 89: 3943–8.PubMedCrossRefGoogle Scholar