Impaired fasting glucose and elevated 180-minute OGTT values predict metformin failure in gestational diabetes...

To evaluate whether oral glucose tolerance test (OGTT)-derived metabolic abnormalities and maternal characteristics predict metformin failure in women with gestational diabetes mellitus (GDM).

This retrospective cohort study included women with singleton pregnancies and gestational diabetes mellitus treated with metformin at a tertiary center (2018-2023). Gestational diabetes mellitus was diagnosed using the American Diabetes Association (ADA) two-step approach, consisting of an initial 50-g glucose challenge screening test followed, when abnormal, by a diagnostic 100-g, 3-h oral glucose tolerance test performed under fasting conditions and interpreted according to Carpenter-Coustan criteria (fasting ≥ 95 mg/dL, 1-h ≥ 180 mg/dL, 2-h ≥ 155 mg/dL, and 3-h ≥ 140 mg/dL). Routine screening was generally performed between 24 and 28 weeks' gestation, with earlier testing in high-risk women when clinically indicated. Of 431 women who initiated metformin, 6 discontinued due to adverse effects, leaving 425 for analysis. Impaired fasting glucose (IFG) was defined as fasting OGTT ≥ 95 mg/dL. The primary outcome was metformin failure, defined as subsequent insulin initiation. Multivariable logistic regression included prespecified OGTT-derived phenotypes rather than simultaneous inclusion of all continuous OGTT variables in order to reduce multicollinearity.

Among 425 women, 114 (26.8%) required insulin. These women had higher glucose values at all OGTT time points and a higher prevalence of IFG (41.2% vs 26.4%, p = 0.005). An abnormal 180-min value was also more frequent (21.1% vs 5.1%, p < 0.001). The number of abnormal OGTT values did not differ significantly between groups and was not independently associated with metformin failure. In multivariable analysis, IFG (aOR 1.96, 95% CI 1.25-3.07) and an abnormal 180-min OGTT value (aOR 4.92, 95% CI 2.50-9.66) remained independently associated with metformin failure.

IFG and an elevated 180-min OGTT value may identify women with GDM at higher risk for treatment escalation. These findings should not be interpreted as direct indications for insulin initiation but rather as potential markers of increased risk for metformin failure requiring closer glycemic surveillance.