Effects of simvastatin and metformin on inflammation and insulin resistance in individuals with mild metabolic syndrome.
BACKGROUND
In addition to lipid-lowering and insulin-sensitizing actions, statins (HMG-CoA reductase inhibitors) and metformin may have pleiotropic effects.


OBJECTIVE
To study the effect of simvastatin and metformin on insulin sensitivity and inflammatory markers.


METHODS
Forty-one subjects with body mass index (BMI) 25-39.9 kg/m(2) 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.


RESULTS
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-alpha 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.


CONCLUSIONS
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.
Bulcão
Caroline
C
Division of Endocrinology, Department of Internal Medicine, Federal University of São Paulo, São Paulo, Brazil. cbulcao@uol.com.br
Ribeiro-Filho
Fernando Flexa
FF
Sañudo
Adriana
A
Roberta Ferreira
Sandra G
SG
D000293:Adolescent; D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006706:Homeostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*
D001055:Apolipoproteins B; D015415:Biomarkers; D001786:Blood Glucose; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D002097:C-Reactive Protein; D008687:Metformin; D019821:Simvastatin