Original Research Article

American Journal of Cardiovascular Drugs

, Volume 7, Issue 3, pp 219-224

First online:

Effects of Simvastatin and Metformin on Inflammation and Insulin Resistance in Individuals with Mild Metabolic Syndrome

  • Caroline BulcãoAffiliated withDisciplina de Endocrinologia, Universidade Federal de São Paulo Email author 
  • , Fernando Flexa Ribeiro-FilhoAffiliated withDisciplina de Endocrinologia, Universidade Federal de São Paulo
  • , Adriana SañudoAffiliated withPGS Medical Statistics
  • , Sandra G. Roberta FerreiraAffiliated withDepartment of Nutrition, School of Public Health, University of São Paulo

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access



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.