In PCOS without Obesity, Metformin Plus Contraceptives Could Be More Beneficial than Contraceptives Alone

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A systematic review and meta-analysis of data from more than a dozen RCTs provide a comprehensive overview of the effects of metformin plus oral contraceptives compared to oral contraceptives alone in women with polycystic ovary syndrome without obesity.

Combining data from 14 randomized clinical trials, new research suggests combination therapy with oral contraceptives and metformin could be more beneficial treatment than oral contraceptives alone for management of polycystic ovary syndrome (PCOS) in patients without obesity.1

A systematic review and meta-analysis performed by investigators from the Department of Obstetrics and Gynecology at Chengdu Second People’s Hospital in China, results of the study provide an overview of the efficacy and safety of combination therapy in this patient population, which investigators suggest is often overlooked in clinical research.

“Currently, 20%-50% of the women with PCOS are of normal weight or lean. Therefore, it is of considerable significance to explore whether this therapy exerts similar beneficial effects on non-obese PCOS patients,” wrote investigators.1

Citing the absence of previous systematic review and meta-analyses comparing the effects of oral contraceptives plus metformin against oral contraceptives alone on glucose and lipid metabolism in patients with PCOS without obesity, a team led by Xiaoli Wang launched the current research endeavor with the intent of conducting a comprehensive systematic review and meta-analysis to evaluate the effect of this treatment approach. With this in mind, investigators designed their study as a systematic review and meta-analysis leveraging data published within the PubMed, EMBASE, Cochrane Library, and databases from inception through April 30, 2022.1

Searching for randomized clinical trials comparing oral contraceptives plus metformin against oral contraceptives alone in reproductive-aged women published in English, the investigators' initial search identified 422 studies. Of these, 30 were selected for full-text review. Investigators excluded 16 studies due to not meeting eligibility requirements, which yielded a group of 14 controlled trials with a population of 707 women for inclusion. This population of 707 women had an age range of 16-40 years and a mean BMI of 30 kg/m2.1

Upon analysis, results indicated adherence to oral contraceptives plus metformin was associated with significantly modified fasting glucose (mean difference [MD], -0.21 [95% CI, -0.31 to -0.12]; P <.00001) and fasting insulin (MD, -2.54 [95% CI, -4.04 to -1.04]; P < .0009) at study completion compared to oral contraceptives alone. Additionally, no statistically significant difference was observed in the homeostasis model of insulin resistance (MD, -026 [95% CI, -0.58 to 0.05]; P=.1), high-density lipoprotein cholesterol (MD, 0.06 [95% CI, -0.03 to 0.15]; P=.2), low-density lipoprotein cholesterol (MD, -0.05 [95% CI, -0.15 to 0.05] P=.37), total cholesterol (MD, -0.04 [95% CI, -0.23 to 0.16]; P=.72), or triglycerides (MD, 0.02 [95% CI, -0.04 to 0.09]; P=.51) at study completion based on treatment.1

Investigators noted multiple limitations to consider before overinterpretation of the results of their study. Specific limitations noted by investigators included the use of only 4 databases, lack of uniformity regarding diagnostic criteria for PCOS, study results may have been impacted by a lack of strict adherence to a BMI limit, and varying dosing durations, which could lead to inconclusive results regarding efficacy.

“This study compared oral contraceptives plus metformin and oral contraceptives alone for metabolism effects of nonobese PCOS patients and indicated that the use of oral contraceptives in combination with metformin may be a better option for non-obese PCOS patients,” investigators wrote in their synopsis.1


  1. Wu L, Liu Y, Huang X, et al. Oral contraceptives (OCs) in combination with metformin versus OCs alone on metabolism in non-obese polycystic ovary syndrome(PCOS): a meta-analysis and systematic review of randomized controlled trials(RCTs) [published online ahead of print, 2023 Feb 17]. Clin Endocrinol (Oxf). 2023;10.1111/cen.14895. doi:10.1111/cen.14895