Effect of rimonabant and metformin on oxidative stress in obese patients with polycystic ovary syndrome (PCOS)
Myint M Aye1, John Shepherd2, Liwei Cho1, J M Ng1, Anne Marie Coady2, Eric S Kilpatrick2, Stephen L Atkin1 & Thozhukat Sathyapalan1
Background: Insulin resistance and obesity are characteristic features of PCOS. Oxidative stress leads to the formation of lipid peroxidation products in the skeletal muscles and has the potential to interfere with insulin signaling and thereby contribute to insulin resistance. Malondialdehyde (MDA) is a lipid peroxidation end product and is widely used as a marker of oxidative stress.
Rimonabant has been shown to reduce weight and insulin resistance in obese PCOS patients. Pavlovic et al. (2000) found that metformin reduced MDA level in patients with type 2 diabetes mellitus with average body mass index (BMI) 31 kg/m2. This study was conducted to determine the effect of rimonabant and metformin on oxidative stress in obese patients with PCOS.
Subjects and methods: A randomized open labelled parallel study of metformin and rimonabant for 12 weeks in 20 patients with PCOS with a mean BMI 37 kg/m2 was undertaken. MDA was measured before and after treatment with either metformin or rimonabant.
Results: MDA decreased (0.81±0.14 vs 0.72±0.89 μmol/l, P=0.03, 95% CI 0.010.16) after treatment with rimonabant, but not following metformin treatment (0.77±0.16 vs 0.89±0.23 μmol/l, P=0.17 CI −0.300.07). The baseline MDA were comparable (0.81±0.13 vs 0.77±0.16 μmol/l, P=0.55) in the rimonabant and metformin groups. However, rimonabant group showed statistically significant reduction of MDA (9.6±12.7 vs −17.9±27%, P=0.01, CI 7.547.6) compared to metformin group.
Conclusion: Rimonabant reduced lipid peroxidation likely through weight reduction, and improved insulin resistance, that was not seen with metformin. The negative result for metformin may reflect the reported lack of its efficacy in patients with a higher body mass index over 31.