BACKGROUND AND PURPOSE:

• Women with polycystic ovary syndrome (PCOS) experience higher gestational weight gain compared to matched controls
• Metformin can induce weight loss through mechanisms that suppress appetite and improve leptin sensitivity
• Molin et al. (BJOG, 2021) examined gestational weight gain in women with PCOS and the impact of metformin

METHODS:

• Secondary analysis of patients in RCTs (2005 to 2017)
  • 2 randomized, double-blind, placebo-controlled multi-centered trials studying the effect of metformin on pregnancy complications in PCOS (PregMet and PregMet2)
• Population
  • Pregnant individuals with PCOS who were randomized to metformin or placebo
  • A prospective cohort of healthy pregnant individuals
  • BMI <30 | Nulliparous | Singleton
• Study design
  • PCOS diagnosis based on Rotterdam Criteria
  • Metformin Dose: 2000 mg daily from inclusion at 5 to 13 weeks until delivery
  • Serum levels of the following appetite regulating hormones in the first and third trimesters were measured
    • Leptin
    • Ghrelin
    • Allopregnanlone
    • Soluble leptin receptor (sOB-R)
• Primary outcome
  • Excessive gestational weight gain relative to BMI (according to 2009 Institute of Medicine guidelines)
  • Leptin sensitivity as measured by
    • Serum leptin/sOB-R ratio
    • Free-leptin-index (FLI)

RESULTS:

• PCOS-Metformin: 36 individuals | PCOS-Placebo: 37 | Healthy controls: 15
• BMI median (min-max range)
  • PCOS-Metformin: 23.4 (19.3 to 29.8)
  • PCOS-Placebo: 24.2 (19.6 to 29.7)
• Overall prevalence of excessive gestational weight gain: 44%
• Compared to health controls, women with excessive gestational weight gain had
  • Higher first and third trimester FLI: P<0.001
  • Lower third trimester allogrananolone: P=0.003
• The prevalence of excessive gestational weight gain was lower in women with PCOS receiving metformin vs those receiving placebo
  • PCOS-Metformin: 28%
  • PCOS-Placebo: 62%
  • Odds ratio (OR) 0.4 (95% CI, 0.2 to 0.8); P=0.005
• Women on metformin were more likely to gain weight below recommendations
  • PCOS-Metformin: 33%
  • PCOS-Placebo: 8%
  • OR 4.1 (95% CI, 1.5 to 15.5); P = 0.01
• FLI decreased during pregnancy in women with PCOS taking metformin, but stayed the same in women with PCOS receiving placebo and healthy controls (P=0.01)
• Throughout pregnancy, all groups had comparable levels of ghrelin and allopregnanolone

CONCLUSION:

• For women with PCOS, taking metformin in pregnancy reduced the rates of excessive gestational weight gain and improved leptin sensitivity
• The authors state

Metformin appears effectively to counteract leptin resistance and prevent eGWG in PCOS

However, nearly one-third over-responded in our study and gained below recommendations, all of whom had BMI <25

Awareness of this possible side-effect is warranted, as inadequate GWG may have negative implications for pregnancy outcome

Learn More – Primary Sources:

Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome: a longitudinal, placebo-controlled study

Related ObG Topics:

RCT Results: Does Weight Loss Prior to Pregnancy Affect Gestational Weight Gain?

Recommended Weight Gain and Obesity Management in Pregnancy

Can a Smartphone ‘Diet and Activity’ App Impact Gestational Weight Gain?

Is There an Association Between High or Low Weight Gain and Maternal and Infant Outcomes?