Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label …

CT Pau, C Keefe, J Duran… - The Journal of Clinical …, 2014 - academic.oup.com
CT Pau, C Keefe, J Duran, CK Welt
The Journal of Clinical Endocrinology & Metabolism, 2014academic.oup.com
Context: Although metformin is widely used to improve insulin resistance in women with
polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent
effects on insulin sensitivity and variability in treatment response. Objective: The aim of the
study was to delineate the effect of metformin on glucose and insulin parameters, determine
additional treatment outcomes, and predict patients with PCOS who will respond to
treatment. Design and Setting: We conducted an open-label, interventional study at an …
Context
Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response.
Objective
The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment.
Design and Setting
We conducted an open-label, interventional study at an academic medical center.
Subjects
Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study.
Interventions
Subjects underwent fasting blood sampling, an IV glucose tolerance test, dual-energy x-ray absorptiometry scan, transvaginal ultrasound, and measurement of human chorionic gonadotropin-stimulated androgen levels before and after 12 weeks of treatment with metformin extended release 1500 mg/d. Interval visits were performed to monitor anthropometric measurements and menstrual cycle parameters.
Main Outcome Measures
Changes in glucose and insulin parameters, androgen levels, anthropometric measurements, and ovulatory menstrual cycles were evaluated.
Results
Insulin sensitivity did not change despite weight loss. Glucose effectiveness (P = .002) and the acute insulin response to glucose (P = .002) increased, and basal glucose levels (P = .001) decreased after metformin treatment. T levels also decreased. Women with improved ovulatory function (61%) had lower baseline T levels and lower baseline and stimulated T and androstenedione levels after metformin treatment (all P < .05).
Conclusions
Using an IV glucose tolerance test, which distinguishes improvements in glucose effectiveness and insulin sensitivity, metformin does not improve insulin sensitivity in women with PCOS but does improve glucose effectiveness. The improvement in glucose effectiveness may be partially mediated by decreased glucose levels. T levels also decreased with metformin treatment. Ovulation during metformin treatment was associated with lower baseline T levels and greater T and androstenedione decreases during treatment, but not with insulin or LH levels. Thus, the action of metformin in PCOS primarily affects glucose levels and steroidogenesis, which may be mediated by mechanisms that affect both pathways, such as inhibition of mitochondrial complex I.
Oxford University Press