Metformin Improves CVD Markers in PCOS: Latest 2024 Research Update

Metformin decreases carotid intima-media thickness (CIMT) and improves flow-mediated dilation (FMD) in patients with polycystic ovary syndrome (PCOS), a recent meta-analysis has reported.

This meta-analysis is the first of its kind to specifically assess metformin’s effects on cardiovascular disease (CVD) risk indicators - CIMT and FMD- among individuals with PCOS.

The meta-analysis included 12 studies with a total of 248 patients, comprising five randomized controlled trials (RCTs), five non-RCTs, and two cross-sectional studies. Metformin doses ranged from 1500 mg to 2550 mg daily, with most studies administering either 850 mg twice daily or 500 mg three times daily.

The research encompassed three studies conducted in Asia, eight in Europe, and one in America. The findings were published in the July 2024 issue of BMC Women’s Health.

In the analysis, the endpoint group refers to measurements taken after metformin treatment, while the baseline group represents measurements taken prior to treatment.

Key Findings on the Effect of Metformin on PCOS Patients

1. Effect on carotid intima-media thickness (CIMT): In a total of seven studies involving 192 patients, metformin significantly reduced CIMT in the endpoint group compared to the baseline, with a mean difference (MD) of -0.11 (95% CI: -0.21 to -0.01, p=0.04). Notably, European PCOS patients showed a substantial reduction (p<0.001). In non-randomized controlled trials, CIMT was significantly lower in the endpoint group (p<0.001), while changes noted in RCTs (p=0.220) and cross-sectional studies (p=0.110) were not statistically significant.

2. Effect on flow-mediated dilation (FMD): Nine studies with 171 patients assessed the effects of metformin on FMD. The endpoint group demonstrated a significant increase in FMD compared to the baseline, with a mean difference of 3.25 (95% CI: 1.85 to 4.66, p<0.01). Specifically, patients in the RCT group exhibited a notable increase in FMD (MD=4.42, 95% CI: 3.15 to 5.69, p<0.001), while those in the non-RCT group also experienced a significant increase (MD=2.41, 95% CI: 0.51 to 4.30, p=0.010).

3. Nitric oxide-mediated dilation (NMD): Four studies involving 59 patients provided data on NMD. In non-RCTs, NMD was significantly higher in the endpoint group than in the baseline group (MD=1.61, 95% CI: 0.23 to 2.99, p=0.020).

Implications for PCOS Treatment

Polycystic ovary syndrome (PCOS) is often associated with insulin resistance and hyperinsulinemia, which can lead to elevated serum testosterone levels and disrupted lipid metabolism, subsequently increasing CVD risk. Metformin, commonly prescribed for PCOS, acts as an insulin sensitizer, enhancing glucose control and lipid metabolism.

In line with these findings, the American Society for Reproductive Medicine (ASRM) recommends metformin as a first-line treatment for PCOS patients exhibiting insulin resistance or impaired glucose tolerance. Additionally, the European Association for the Study of Diabetes (EASD) includes metformin in treatment guidelines for managing metabolic abnormalities in this population.

The Federation of Obstetric and Gynaecological Societies of India (FOGSI) and the Indian College of Obstetricians & Gynaecologists (ICOG) recommends metformin for adult women with PCOS and a BMI ≥ 25 kg/m² to manage weight and metabolic outcomes, alongside lifestyle modifications (grade A). It can also be considered for adolescents with the same BMI if lifestyle changes are ineffective. Metformin is particularly beneficial for those at high metabolic risk, including women with diabetes risk factors or impaired glucose tolerance (grade B).

This meta-analysis highlights the cardiovascular benefits of metformin for patients with PCOS, underscoring its role in reducing CIMT and improving FMD. These findings support the use of metformin in managing both reproductive & metabolic aspects of PCOS, ultimately aiding in the reduction of cardiovascular risk in this population.

References:

1. Wang, Fang et al. “Effects of Metformin on CIMT and FMD in PCOS patients: a systematic review and meta-analysis.” BMC women's health vol. 24,1 426. 26 Jul. 2024, doi:10.1186/s12905-024-03275-w

2. FOGSI-ICOG. Good Clinical Practice Recommendations GCPR on Update in Managing PCOS in Women 2023. Retrieved on 25th September 2024 from https://www.fogsi.org/wp-content/uploads/2024/08/Binder_Update-in-Managing-PCOS-in-Women.pdf