title: Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We conducted an open-label, interventional study at an academic medical center.
  
  
  METHODS
  Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Cindy T
authors.initials: CT
authors.lastname: Pau
authors.forename: Candace
authors.initials: C
authors.lastname: Keefe
authors.forename: Jessica
authors.initials: J
authors.lastname: Duran
authors.forename: Corrine K
authors.initials: CK
authors.lastname: Welt
mesh_terms: D000328:Adult; D001786:Blood Glucose; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008687:Metformin