Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome

Mean insulin resistance (IR) is greater and it is also more variable in overweight women with polycystic ovarian syndrome (PCOS) compared to weight matched controls. Whilst treatment will reduce the mean IR, it is not known if the IR variability is also reduced. To compare the change in IR and its variability before and after treatment with insulin sensitization through metformin and pioglitazone, compared to that induced by weight loss with orlistat. Randomized, open labelled parallel study. Endocrinology outpatient clinic at a referral centre. Thirty obese PCOS patients [BMI 36.0 +/- 1.2 kg/m(2) (mean +/- SEM)] participated in the study. The change in biological variability (BV) was assessed by measuring IR (homeostasis model assessment method) at 4-day intervals on 10 consecutive occasions before and 12 weeks after randomization to metformin, pioglitazone or orlistat. The primary end point of the study was a change in BV of IR. Treatment with pioglitazone, orlistat and metformin reduced the overall IR by 41.0 +/- 4.1%, 19.7 +/- 6.4% and 16.1 +/- 6.8% (P = 0.005, P = 0.013, P = 0.17, respectively) and IR variability by 28.5 +/- 18.0%, 41.8 +/- 11.6% and 23.7 +/- 17.0 (P = 0.20, P = 0.015 and P = 0.28, respectively). Free androgen index reduced significantly with all treatments. Only orlistat reduced both IR and its variability significantly, though all three drugs were effective in reducing hyperandrogenism within the 12-week period of the study.