Myoinositol vs. metformin in women with polycystic ovary syndrome: a randomized controlled clinical trial

Ravn, Pernille; Gram, Freja; Andersen, Marianne S.; Glintborg, Dorte

doi:10.3390/metabo12121183

Cited by 22Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsEndometriosis Research and Treatment

Myoinositol vs. metformin in women with polycystic ovary syndrome: a randomized controlled clinical trial

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Ravn, Pernille, Gram, Freja, Andersen, Marianne S., Glintborg, Dorte·2022·Metabolites

DOI 10.3390/metabo12121183PMC PMC9786218

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Abstract

Polycystic ovary syndrome (PCOS) is associated with insulin resistance. Few randomized controlled trials (RCT) compared myoinositol (MI) with metformin (MET) regarding insulin resistance in PCOS. This was an open-label six-month RCT in women with PCOS (n = 45) with interventions MI 4 g/day or MET 2 g/day. Primary outcome was the homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were fasting glucose, weight, cycle length, lipids, testosterone, adverse effects, quality of life, and depression scores. Median age was 26 years. Body mass was index was 34.4 kg/m2. HOMA-IR was unchanged during MI (p = 0.31) and MET (p = 0.11) (MI vs. MET, p = 0.09). Median fasting glucose changed +0.2 mmol/L during MI (p < 0.001) and −0.1 mmol/L during MET (p = 0.04) (MI vs. MET p < 0.001). Median weight changed −2.3 kg during MI (p = 0.98) and −6.1 kg during MET (p < 0.001) (MI vs. MET, p = 0.02). Median cycle length decreased nine days during MI (p = 0.03) and 13 days during MET (p = 0.03) (MI vs. MET, p = 0.93). High-density lipoprotein (HDL) changed +0.1 mmol/L during MET (p = 0.04) (MI vs. MET, p = 0.07). All other blood parameters and scores of quality of life and depression remained unchanged during MI and MET (all p > 0.06) (MI vs. MET, all p > 0.27). Adverse effects appeared in four women during MI and 16 women during MET (MI vs. MET, p = 0.001). In conclusion, there was no effect on the metabolic outcomes during MI, but positive effects on fasting blood glucose, weight, and HDL during MET. The effect on cycle length was comparable during MI and MET. Adverse effects were less frequent during MI.

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In women with PCOS, gastrointestinal adverse events are less common with myo-inositol than with metformin (6 RCTs, OR 0.09, 95% CI 0.02 to 0.37; moderate certainty).
“In a meta-analysis of 6 trials, GI AEs were less common in the MI group compared with metformin (OR 0.09, 0.02 to 0.37, I2 = 69%, 6 trials, Fig. 5Q) (26, 33, 51-54).”
From Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines (2024) · cites this paper as [52]
Results §3.6 reports significantly fewer GI side effects with myo-inositol than metformin in this PCOS trial (1 versus 12 women). The source is an individual RCT, not the six-trial meta-analysis; it does not report the quoted pooled odds ratio, confidence interval, or moderate-certainty rating. (LLM, conf=0.89)
Experimental — accuracy not yet measured
One included study comparing MI and metformin reported psychological outcomes of depression and quality of life.
“One study comparing MI and metformin reported on psychological outcomes (depression and quality of life) (52).”
From Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines (2024) · cites this paper as [52]

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The Comparative Effects of Myo-Inositol and Metformin Therapy on the Clinical and Biochemical Parameters of Women of Normal Weight Suffering from Polycystic Ovary Syndrome
Gudović, A., Bukumirić, Z., Milinčić, M., Pupovac, M., Andjić, M., Ivanović, K., & Spremović-Radjenović, S. (2024) · Biomedicines · doi:10.3390/biomedicines12020349 · Cited by 15 · see citing works
A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome
Nazirudeen, R., Sridhar, S., Priyanka, R., Sumathi, B., Natarajan, V., Eagappan, S., Raghavan, K. S., & Jayaraman, S. (2023) · Clinical Endocrinology · doi:10.1111/cen.14931 · Cited by 26 · see citing works

Authors: Ravn, P., Gram, F., Andersen, M. S., & Glintborg, D.
Affiliations: University of Southern Denmark (DK)
Odense University Hospital (DK)
Corresponding author: Ravn, Pernille
ORCID: Ravn, Pernille
Andersen, Marianne S.
Glintborg, Dorte
Venue: Metabolites
Publisher: MDPI AG
Published: 2022-11-26
Volume: 12
Issue: 12
Pages: 1183
ISSN: 2218-1989 (ISSN-L)
DOI: 10.3390/metabo12121183
PMC: PMC9786218
OpenAlex: W4310231295
Cited by: 18
References: 44
Citations by year: 2026: 5 · 2025: 3 · 2024: 7 · 2023: 3
FWCI: 2.74
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Metabolites (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
University of Southern Denmark Research Portal (University of Southern Denmark) (acceptedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: BiO4U Ltd., Dublin, Ireland
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
Keywords: polycystic ovary syndrome, myo-inositol, metformin, insulin resistance, HOMA-IR, fasting blood glucose, body weight, menstrual cycle length, HDL cholesterol, adverse effects, quality of life, depression

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Myoinositol vs. metformin in women with polycystic ovary syndrome: a randomized controlled clinical trial

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