Gestational Diabetes: New Data on Treatment, Long-Term Risk

Two new analyses underscore why gestational diabetes deserves attention well beyond delivery. A secondary analysis of a randomized clinical trial published in JAMA Network Open found that starting metformin early in patients with gestational diabetes was associated with fewer insulin initiations. Meanwhile, a national analysis slated for the American Heart Association (AHA) Scientific Sessions 2026 linked a history of gestational diabetes to more advanced cardiovascular-kidney-metabolic (CKM) syndrome among women aged 30 to 79 years.^1,2

Metformin Reanalysis Points to Fewer Insulin Starts

The Early Metformin in Gestational Diabetes (EMERGE) trial was double-masked and placebo-controlled, run at 2 centers in Ireland. It randomly assigned 535 pregnancies to metformin or placebo in addition to medical nutrition therapy. Metformin was started at 500 mg/d and titrated to a maximum of 2500 mg/d, or the maximum tolerated dose, and continued until delivery. The original primary composite outcome was insulin initiation or fasting plasma glucose of 5.1 mmol/L or higher at gestational week 32 or 38. It did not differ significantly between groups, although each individual component favored metformin.¹

For this reanalysis, investigators used generalized pairwise comparisons. This method pits each metformin participant against each placebo participant and ranks outcomes by clinical priority: insulin initiation first, then fasting hyperglycemia at week 32 and week 38. Among 526 pregnancies with primary outcome data, the prioritized composite favored metformin. The win ratio was about 1.46 (95% CI, 1.13-1.89), the net treatment benefit was 13.7 percentage points, and the win odds were 1.34 (P = .004). Put simply, metformin produced an approximately 46% more favorable than unfavorable comparisons among informative pairs.¹

Insulin initiation drove most of the effect (win ratio, 1.68; 95% CI, 1.19-2.38; P = .003). Per the participant flow, 101 of 264 pregnancies in the metformin group initiated insulin, compared with 134 of 262 in the placebo group. Fasting hyperglycemia added little within the hierarchy, although nonprioritized and clinically weighted analyses also favored metformin.¹

Framing the Results for Patients

The authors were clear that the analysis was exploratory and not prespecified and that it did not change the null conclusion of the primary trial. Insulin use was analyzed as a yes-or-no outcome, without its timing, dose, or duration, so the authors cautioned that favorable comparisons should not be read as eliminating insulin use. The trial also did not test metformin, which started only after an inadequate response to nutrition therapy.¹

For pharmacists dispensing metformin during pregnancy, the EMERGE approach of starting low and titrating to the maximum tolerated dose offers a practical reference for counseling on tolerability and adherence. Notably, the trial excluded individuals with intolerance of or contraindication to metformin.¹

Gestational Diabetes History Linked to Advanced CKM Stages

The AHA abstract comes from investigators at the University of California, Davis, and Emory University. They analyzed National Health and Nutrition Examination Survey (NHANES) data from 2007 to March 2020 for 11,181 women aged 30 to 79 years with at least 1 prior pregnancy, representing a weighted 69.9 million women. About 8% reported a history of gestational diabetes. CKM stages were classified using 2023 AHA criteria, which range from stage 0, reflecting no risk factors, to stage 4, reflecting established cardiovascular disease.^2,3

The results were adjusted for sociodemographic and behavioral factors. Women with a history of gestational diabetes had a lower predicted probability of stage 0 (relative risk [RR], 0.58; 95% CI, 0.38-0.79) and stage 1 (RR, 0.70; 95% CI, 0.55-0.85) CKM syndrome. They were also observed to have a higher probability of stage 4 (RR, 1.55; 95% CI, 1.13-1.97). Most women in both groups fell into stage 2, with no significant difference after adjustment, and stage 3 showed a similar but nonsignificant pattern.²

The authors described gestational diabetes as an early sentinel event for long-term CKM progression and called for sustained risk surveillance and targeted prevention. Gestational diabetes history was self-reported, and the data were cross-sectional. The authors also recommended that longitudinal studies are needed to characterize progression after diagnosis.²

For pharmacists, a history of gestational diabetes noted during a medication review or screening encounter may be a cue to ask about follow-up for blood pressure, glucose, lipids, and kidney function. That fits the AHA framework’s emphasis on preventing progression across CKM stages.³

REFERENCES

1. Aguilar Macías DA, Alvarez-Iglesias A, Ferguson JM, et al. Early metformin initiation and glycemic outcomes in gestational diabetes: a secondary analysis of a randomized clinical trial. JAMA Netw Open. 2026;9(11):e2635700. doi:10.1001/jamanetworkopen.2026.35700

2. Choi JY, Arons A, Choi D, Brown SD. Cardiovascular-kidney-metabolic syndrome among women with a history of gestational diabetes: a national analysis using the National Health and Nutrition Examination Survey, 2007-2020. Abstract MDP1252. Presented at: American Heart Association Scientific Sessions 2026; November 6-9, 2026; Chicago, IL.

3. Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association. Circulation. 2023;148(20):1606-1635. doi:10.1161/CIR.0000000000001184