Fact checked byRichard Smith

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October 04, 2023
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Metformin provides glycemic, neonatal benefits for women with gestational diabetes

Fact checked byRichard Smith
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Key takeaways:

  • Women with gestational diabetes who received metformin had lower fasting glucose than those who received placebo.
  • Fewer infants of women in the metformin group were born large for gestational age.

Metformin may lengthen the time until insulin initiation, lower fasting glucose and improve neonatal outcomes for pregnant women with gestational diabetes, according to data from a randomized trial.

In findings presented at the European Association for the Study of Diabetes annual meeting and simultaneously published in JAMA, researchers compared glycemic, maternal and neonatal outcomes for women with gestational diabetes randomly assigned up to 2,500 mg metformin daily with those receiving placebo. The metformin group had a lower mean fasting glucose at 32 and 38 weeks of gestation, and the offspring of women receiving metformin had a lower mean birth weight than the offspring of those receiving placebo.

Metformin reduces the likelihood for large for gestational age among offspring of women with gestational diabetes.
Data were derived from Dunne F. Metformin for the management of GDM: Friend or foe? Presented at: European Association for the Study of Diabetes Annual Meeting; Oct. 2-6, 2023; Hamburg, Germany (hybrid meeting).

“This trial shows that metformin is a safe and effective alternative treatment that women now have the choice to take if they have gestational diabetes,” Fidelma Dunne, MD, PhD, MMed, professor in the College of Medicine, Nursing and Health Sciences at the University of Galway in Ireland, told Healio.

Fidelma Dunne

Dunne and colleagues conducted a phase 3 randomized, double-blind, placebo-controlled trial of pregnant women aged 18 to 50 years diagnosed with gestational diabetes. Participants were enrolled at two sites in Ireland. At diagnosis, women were randomly assigned, 1:1, to metformin and placebo daily until delivery. Participants performed seven-point glucose testing at mealtimes and before bed each day. Laboratory testing was conducted at 32 and 38 weeks of gestation. Birth visits took place within 72 hours of delivery to assess maternal and neonatal outcomes. The primary outcome of the study was a composite of the need to initiate insulin before delivery or having a fasting glucose of 5.1 mmol/L or higher at 32 or 38 weeks of gestation.

Metformin reduces fasting glucose

Of 150 women in the metformin group and 167 women in the placebo group with data available, the risk of meeting the composite outcome of insulin initiation or a fasting plasma glucose level of 5.1 mmol/L or higher was similar between the groups. However, in an alternative time-to-event analysis, women receiving metformin were less likely to initiate insulin than women receiving placebo (HR = 0.66; 95% CI, 0.51-0.85; P = .001). When fasting glucose was analyzed on its own, women in the metformin group had a lower mean fasting glucose at 32 weeks of gestation (mean difference, –0.1 mmol/L; 95% CI, –0.19 to –0.01; P = .03) and 38 weeks of gestation (mean difference, –0.2 mmol/L; 95% CI, –0.28 to –0.09; P < .001) compared with placebo. Postprandial glucose was also lower in the metformin group after lunch and dinner at 32 weeks of gestation and after dinner at 38 weeks compared with placebo. Women receiving metformin gained 0.8 kg of body weight from randomization to delivery compared with a mean 2 kg weight gain for those receiving placebo (P = .003).

“Although the primary composite outcome was similar between groups, there were very important positive impacts on maternal weight gain and fasting and post-meal sugars at weeks 32 and 38,” Dunne told Healio.

Lower birth weight with metformin

Infants from mothers in the metformin group had a lower mean birth weight than offspring of mothers from the placebo group (3,393 g vs. 3,506 g; P = .005). The percentage of infants born large for gestational age was lower in the metformin group vs. placebo (6.5% vs. 14.9%; P = .003). Mean crown-to-heel length was shorter in offspring of mothers from the metformin group compared with placebo (51 cm vs. 51.7 cm; P = .02).

“Caution should continue with metformin and small for gestational age, especially in those where small for gestational age may be more likely, so those with hypertension or nephropathy,” Dunne said during the presentation.

Gastrointestinal adverse events were reported by 24.3% of the metformin group compared with 4.1% of the placebo group (P < .001). Thirteen women in the metformin group discontinued the trial due to gastrointestinal adverse events.

Dunne said more studies are needed to analyzed more metabolic and cardiovascular variables as well as body composition data for infants.

“Future trials should be randomized and placebo-controlled when we’re talking about metformin in pregnancy,” Dunne said during the presentation. “Women should be consented for long-term follow-up. We should give consideration to bio-banking in all of these trials for interrogation of disease mechanisms. Going forward, we should continue to use, as much as possible, core outcome sets and patient-reported outcomes for better data synthesis and meta-analysis.”

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