Grand Rounds

The MiG-TOFU Study: Gestational Diabetes, Metformin and Metabolic Outcomes in Offspring 7 Years Later

long term

Metformin in Gestational diabetes (MiG) trial
- RCT of women with GDM, randomized to either metformin (plus supplemental insulin if required) or insulin
- Similar outcomes although metformin group had increased rate of preterm birth (12/1% vs 7.6%, p=0.04) and neonates with lower rates of severe hypoglycemia (3.3% vs 8.1%, p=0.009)
- Long-term offspring follow-up (TOFU) data are lacking and studies are ongoing
Outcomes at 2 years of age in offspring of women with GDM treated with metformin showed similar total body fat percent, but greater subscapular and biceps skinfolds, as well larger upper arm circumferences
Rowan et al. (BMJ Open Diabetes Research & Care, 2018) present the 7 year follow up data from the MiG trial

Longitudinal follow-up of women recruited to MiG-TOFU study
Women were randomized into groups that received
- Metformin
- Insulin
- Matching control
Children were assessed in Adelaide (7 year follow up) and then Auckland (9 year follow up) using multiple tools
- Anthropometry
- Bioimpedance analysis (BIA)
- Dual-energy X-ray absorptiometry (DXA)
- Magnetic resonance imaging (MRI)
- Fasting bloods

Total participants: 208
- 109 Adelaide (7 year) and 99 Auckland (9 year)
There were no differences in offspring measures at 7 years
At 9 years in Auckland, metformin offspring were
- Larger by measures of weight, arm and waist circumferences, waist:height (p<0.05)
- BMI, triceps skinfold (p=0.05)
- DXA fat mass and lean mass (p=0.07)
- MRI abdominal fat volume (p=0.051)
All other measures were similar

Metformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7-9 years
However, metformin-exposed children were larger at 9 years
Authors state that overall, data related to long-term metformin use is reassuring but further research is needed to understand the findings at 9 years

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