Endocrine Abstracts (2007) 13 OC15

Biological variability of insulin resistance in polycystic ovarian syndrome after treatment with Metformin, Orlistat and Pioglitazone

Li Wei Cho1, Susana Gonzalez1, Stephen Holding2, Eric Kilpatrick2 & Stephen Atkin1

1University of Hull, Hull, United Kingdom; 2Department of Clinical Chemistry, Hull Royal Infirmary, Hull, United Kingdom.

Background: A previous study suggested an increased absolute and intraindividual variability of insulin resistance (IR) in overweight women with polycystic ovarian syndrome (PCOS) which may contribute to the increase in cardiovascular risk. There had been no previous data on the change in variability of IR in PCOS with treatment.

Methods: PCOS women were recruited using the Rotterdam criteria [mean age (±S.E.M.) 26.4(±1.5)yrs and body mass index 36.0(±1.2) kg/m2]. Subjects were allocated to metformin (500 mg three times daily), orlistat (120 mg three times daily) or pioglitazone (45 mg once daily). Fasting blood was collected on 10 consecutive occasions at 4-day intervals before and 3 months after treatment. The mean HOMA-IR [(insulin x glucose)/22.5] was calculated from the pre and post treatment samples. All groups were closely matched for age and BMI. None were diabetic or received treatment that will alter IR. Local ethical committee approval had been obtained.

Results: HOMA-IR reduced with all treatments with the reduction in orlistat (P=0.013) and pioglitazone (P=0.005) statistically significant. The intraindividual variability reduced with all treatments but was again significant only for orlistat (P=0.009) and pioglitazone (P=0.047). BMI reduced significantly with metformin (P=0.013) and orlistat (P=0.005), with a trend to increase with pioglitazone (P=0.059).

Conclusion: Our data suggests that whilst metformin, orlistat and pioglitazone all reduce IR, Only orlistat and pioglitazone reduce IR significantly in this obese population, in accord with studies showing that metformin is less effective in individuals with a BMI greater than 37. Furthermore, intraindividual variability in IR was also seen to reduce with all three treatments but a significant reduction was only demonstrated with orlistat and pioglitazone. Therefore, by improving both these aspects of IR, orlistat and pioglitazone may be more effective than metformin in treating the insulin resistance (and its associated metabolic sequelae) in obese patients with PCOS.

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