Does Metformin Therapy During Pregnancy Affect Metabolic Health in PCOS?

Participants in the PregMet study were randomly assigned to metformin (1000 mg twice daily) or placebo from their first trimester through delivery.
Participants in the PregMet study were randomly assigned to metformin (1000 mg twice daily) or placebo from their first trimester through delivery.

Metformin therapy has no long-term impact on metabolic health in women with polycystic ovarian syndrome (PCOS), according to research presented at ENDO 2017: the 99th Annual Meeting & Expo, April 1-4, in Orlando, Florida.1

Researchers at the Norwegian University of Science and Technology in Trondheim, Norway conducted a follow-up assessment of data from the PregMet study (Metformin in Pregnant PCOS Women; ClinicalTrials.gov identifier NCT00159536)2 to investigate the long-term metabolic health of women with PCOS.

Participants in the original randomized controlled trial randomly received either metformin (1000 mg twice daily) or placebo from the first trimester of their pregnancy through delivery, with therapy stopped at delivery.

Half of the 258 original participants took part in the follow-up study; median follow-up time was 7.6 years (range, 4.9-11.1). Control subjects comprised 48 healthy mothers.

At baseline (inclusion in the PregMet study), no difference was noted between women with PCOS who participated in the follow-up study and women who declined to participate; however, women with PCOS had a higher body mass index (BMI, 28.6±6.6 kg/m2 vs 23.0±3.6 kg/m2; P <.001) as well as higher systolic and diastolic blood pressures vs controls (118±12 mm Hg vs 114±10 mm Hg; P =.045 and 73±10 mm Hg vs 69±9 mm Hg; P =.03, respectively).

Women in the healthy control group were typically younger (34.4±3.7 vs 38.2±4.6 years; P <.001) and had a shorter follow-up time (5.5±0.8 vs 7.9±1.7 years; P <.001). Compared with patients with PCOS, their BMI was also lower (29.6±6.9 kg/m2 vs 23.9±3.9 kg/m2; P <.001). BMI change was similar over time in both groups, although women with PCOS had increased muscle mass vs healthy controls (28.6±3.8 kg vs 26.5±2.9 kg; P =.04).

At 5 to 11 years after pregnancy, the researchers noted no differences in the women who had been received metformin or placebo with respect to BMI, blood pressure, or muscle mass and visceral fat area. In addition, serum lipid, fasting glucose, insulin C-peptide, and hemoglobin A1c values were all similar in the 2 groups.

Among all participants, 20% of women in the PCOS group and 8.3% of women in the control group were diagnosed with metabolic syndrome (P =.07).

“Metformin therapy in pregnancy did not affect [the] long-term metabolic health of [women with] PCOS,” the investigators concluded. “Significant metabolic disturbances were present at 5 [to] 11 years follow-up in women with PCOS compared [with] control women.” 

References

  1. Underdal MO, Stridsklev S, Andresen MS, Vanky E. Metabolic health in women with PCOS — 5-11 years' follow-up after metformin or placebo in pregnancy. Abstract 082. Presented at: ENDO 2017: the 99th Annual Meeting & Expo. April 1-4, 2017; Orlando, Florida
  2. Vanky E, Stridsklev S, Heimstad R, et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab. 2010;95(12):e448-e455. doi:10.1210/jc.20100-0853 
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