Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial

Abstract

BackgroundObesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m2. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes. Further information evaluating alternative strategies is required.The aims of this randomised controlled trial are to assess whether the use of metformin as an adjunct therapy to dietary and lifestyle advice for overweight and obese women during pregnancy is effective in improving maternal, fetal and infant health outcomes.MethodsDesign: Multicentre randomised, controlled trial.Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit.Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using an online computer randomisation system, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth.Treatment Schedules: Women randomised to the Metformin Group will receive a supply of 500 mg oral metformin tablets. Women randomised to the Placebo Group will receive a supply of identical appearing and tasting placebo tablets. Women will be instructed to commence taking one tablet daily for a period of one week, increasing to a maximum of two tablets twice daily over four weeks and then continuing until birth. Women, clinicians, researchers and outcome assessors will be blinded to the allocated treatment group.All women will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant), and three telephone calls over the course of their pregnancy, in which they will be provided with dietary and lifestyle advice, and encouraged to make change utilising a SMART goals approach.Primary Study Outcome: infant birth weight >4000 grams.Sample Size: 524 women to detect a difference from 15.5% to 7.35% reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two-tailed).DiscussionThis is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12612001277831, prospectively registered 10th of December, 2012.

Effect of metformin in addition to dietary and lifestyle advice for pregnant women who are overweight or obese: the GRoW randomised, double-blind, placebo-controlled trial

“…The study protocol 12 (Supplementary File 1) was approved by the Women's and Children's Health Network Human Research Ethics Committee with local institutional approval at each site, and registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12612001277831). Participating women provided written informed consent.…”

Evaluation of a smartphone nutrition and physical activity application to provide lifestyle advice to pregnant women: The SNAPP randomised trial

“…These trials recruited women at 10 to 20 weeks' gestation, from public maternity hospitals across metropolitan Adelaide, South Australia. In brief, the GRoW randomised trial is recruiting pregnant women with BMI ≥ 25 kg/m 2 to evaluate the effects of metformin use during pregnancy, as an adjuvant therapy to a dietary and lifestyle intervention on pregnancy and birth outcomes (Dodd et al, ). The OPTIMISE randomised trial is recruiting pregnant women with BMI = 18.5–24.9 kg/m 2 to evaluate the effects of an antenatal dietary and lifestyle intervention on pregnancy and birth outcomes.…”

“…Women who were randomised to the Lifestyle Advice Only Group received a comprehensive lifestyle intervention involving a combination of dietary, physical activity, and behavioural strategies, as have been described and utilised previously (Dodd, ; Dodd et al, ). Over the course of pregnancy, women attended two face‐to‐face sessions (within 2 weeks of trial entry and 28 weeks' gestation) with a dietitian and a face‐to‐face session at 36 weeks' gestation with a research assistant were provided with specific written materials.…”

ADIPS 2020 guideline for pre‐existing diabetes and pregnancy

“…Contributing to the data for early pregnancy use of metformin are studies of metformin in women with polycystic ovary syndrome who require fertility assistance and studies of metformin in women with obesity aiming to prevent gestational diabetes (unsuccessfully). [77][78][79][80]…”

“…The generalisability of these data to women with type 2 diabetes, who usually require glucose‐lowering agents throughout pregnancy, is unclear. Contributing to the data for early pregnancy use of metformin are studies of metformin in women with polycystic ovary syndrome who require fertility assistance and studies of metformin in women with obesity aiming to prevent gestational diabetes (unsuccessfully) 77–80 …”