Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials

Gynecol Endocrinol. 2019 Mar;35(3):198-206. doi: 10.1080/09513590.2018.1540578. Epub 2019 Jan 7.


Metformin (MET), the most commonly used insulin sensitizer, is the reference off-label drug for the treatment of polycystic ovary syndrome (PCOS), worldwide. However, its use may be limited mainly by gastrointestinal adverse effects. Myo-inositol (MI), a well-recognized food supplement, also represents an evidence-based treatment for PCOS women, popular in many countries. Our aim is to provide a systematic review of the literature and a meta-analysis which compares these two treatments, for their short-term efficacy and safety in PCOS patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). RCTs were identified from 1994 through 2017 using MEDLINE, Cochrane Library, PubMed, and ResearchGate. Included studies were limited to those one directly comparing MET to MI on several hormones changes. Standardized mean difference (SMD) or risk ratios (RRs) with 95% CIs were calculated. Changes in fasting insulin was the main outcome of measure. Six trials with a total of 355 patients were included. At the end of treatment, no difference between MET and MI was found on fasting insulin (SMD=0.08 µU/ml, 95% CI: -0.31-0.46, p=.697), HOMA index (SMD =0.17, 95% CI: -0.53-0.88, p=.635), testosterone (SMD= -0.01, 95% CI: -0.24-0.21, p=.922), SHBG levels (SMD= -0.50 nmol/l, 95% CI: -1.39-0.38, p=.263) and body mass index (BMI) (SMD= -0.22, 95% CI: -0.60-0.16, p=.265). There was strong evidence of an increased risk of adverse events among women receiving MET compared to those receiving MI (RR =5.17, 95% CI: 2.91-9.17, p<.001). No differences were found in the effect of MET and MI on short-term hormone changes. The better tolerability of MI makes it more acceptable for the recovery of androgenic and metabolic profile in PCOS women.

Keywords: BMI; HOMA index; PCOS; SHBG; androstenedione; fasting insulin; metformin; myo-inositol; side effects; testosterone.

Publication types

  • Meta-Analysis

MeSH terms

  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Inositol / therapeutic use*
  • Metformin / therapeutic use*
  • Off-Label Use
  • Polycystic Ovary Syndrome / drug therapy*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Hypoglycemic Agents
  • Inositol
  • Metformin