Metformin vs Metformin plus Myo-Inositol and D-chiro-inositol

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Metformin vs Metformin plus Myo-Inositol and D-chiro-inositol

Comparison of Clinical, Metabolic and Hormonal Effects of Metformin Versus Combined Therapy of Metformin With Myoinositol Plus D-Chiro-Inositol in Women With Polycystic Ovary Syndrome (PCOS): A Randomized Controlled Trial


The use of insulin-sensitizers such as metformin is commonly prescribed to women with PCOS and insulin resistance.

Studies of natural alternatives, Myo-inositol and D-chiro-inositol, have also shown beneficial effects.

Myo-inositol improves ovarian function and follicle-stimulating hormone (FSH) signalling, increases sex hormone-binding globulin (SHBG) and decreases levels of total and free testosterone.

D-chiro-inositol on the other hand has a more indirect effect, by increasing glycogen synthesis and reducing insulin levels, which indirectly alters insulin-mediated testosterone synthesis.

The unique mechanism of action of all 3 insulin-sensitizers raises an interesting question, is combined therapy more effective than mono-therapy?


To investigate the effect of metformin alone versus metformin with Myo-inositol plus D-chiro-inositol in women with PCOS.


Women recently diagnosed with PCOS (Rotterdam criteria), aged 18 to 45 years were prospectively recruited for this trial.

During initial assessment, any woman with abnormal kidney or liver function test results, uncontrolled thyroid disorders, hyperprolactinemia, congenital adrenal hyperplasia, Cushing’s syndrome, androgen-secreting tumors, on PCOS specific medication or at risk of an adverse reaction to therapy, was automatically excluded from the study.

Women with a BMI of 23-26.9 kg/m2 were classified as overweight, while a BMI ≥27 kg/m2 was defined as obese, using the Asian BMI scale. Hirsutism was calculated using the modified Ferriman Galway scoring system. Biochemical and hormonal assessments was carried out during the follicular phase (cycle day 2-3) of each participant.

Participants were randomized into 2 groups, with Group 1 given Metformin (500mg) to take twice daily for 6 months, while Group 2 was given Metformin (500mg twice/day), Myo-inositol (550mg daily), and D-chiro-inositol (150mg twice/day) to take for 6 months.

All measurements were repeated at the end of the trial, with any changes in clinical, metabolic or hormonal parameters as the primary study outcome.


Of the initial 106 women who enrolled in the study, 29 were automatically excluded, and 5 were lost to follow up. Each group had a final sample size of 36 women each.

Mean baseline clinical characteristics of the groups revealed no statistically significant differences between the 2 groups, although BMI (25.3 vs. 23.4 kg/m2) and waist circumference (87.4 vs. 82.1 cm) was slightly higher among the women in Group 2, causing a significant difference in hip circumference (102.5 vs. 97.4 cm) at baseline.

At the end of the trial global acne scores (2.8 vs. 4.4), and proportion of irregular cycles (38.9 vs 63.9 %), was significantly better in Group 2, with no longer any difference in mean BMI (23.3 vs 23.4 kg/m2) between Group 1 and 2, resulting in similar waist and hip circumferences (P>0.2).

Analysis of hormonal parameters showed similar differences with significant improvements in luteinizing hormone (LH) levels (6.1 vs 9.1 IU/L) via combined therapy leading to improved LH:FSH ratios (1.11 vs. 1.39) when compared to metformin treatment alone. Interestingly total testosterone levels increased slightly in the metformin only group (54.6 vs. 49.2 ng/dL) following the trial while levels were mostly maintained in the combined therapy group (47.6 vs 49.3 ng/dL).

Finally, analysis of metabolic parameters, comparing combined therapy to metformin only treatment, at the end of 6 months, showed significant improvement in cholesterol (131.6 vs. 146.8 mg/dL), HDL (47.3 vs. 41.5 mg/dL), LDL (85.9 vs. 106.2 mg/dL) and postprandial insulin (35.3 vs. 57.8 mIU/L) levels, demonstrating clearly that treatment of PCOS with metformin is enhanced by the addition of Myo-inositol and D-chiro-inositol.

Detailed analysis of the metabolic results also revealed a more signifcant improvement in both triglyceride and fasting insulin levels among women in Group 2. Although these women began the trial with moderately worse triglyceride (114.6 vs 91.8 mg/dL) and fasting insulin (20.3 vs. 15.8 mIU/L) levels compared to group 1, by the end of the trial this difference had all but disappeared between the 2 groups (P>0.3).


In this study, the combination of metformin plus Myo-Inositol and D-chiro-inositol taken together, significantly increased the number of regular menstrual cycles (61.1 vs. 36.1 %), while improving LH (6.1 vs. 9.1 IU/L), cholesterol, HDL, LDL and post-eating insulin levels, compared to metformin alone.


  1. Small overall group sizes
  2. Safety of combined therapy not assessed


No external funding was declared for this study.


High-density lipoproteins also known as the “good” cholesterol.

Male pattern hair growth.

Low-density lipoproteins also known as the “bad” cholesterol.

The probability that a result occurred by random chance.

The period after dinner or lunch.

Similar studies

Chirania K, et al. (2017). A randomised clinical trial comparing myoinositol and metformin in PCOS.

Fruzzetti F, et al. (2017). Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS).

Benelli E, et al. (2016). A combined therapy with myo-inositol and D-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women.


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