Semaglutide after GDM: the SERENA trial

Women who develop gestational diabetes carry a substantially elevated risk of type 2 diabetes for the rest of their lives. A Belgian multicentre team is now testing whether semaglutide can interrupt that trajectory in the critical postpartum window, when prediabetes is already present and the window for prevention is open. The trial is called SERENA^[1], and its protocol was published in BMJ Open on 23 July 2026.

Why this window matters

Gestational diabetes (GDM) is not a transient inconvenience that resolves after delivery. A 2020 systematic review and meta-analysis of 20 studies covering more than 1.3 million women found that prior GDM carries roughly a ten-fold higher relative risk of developing type 2 diabetes compared with normoglycaemic pregnancies^[2]. A separate 2021 meta-analysis of 129 studies reported that 17% of women with GDM history went on to develop type 2 diabetes, with approximately one-third of those diagnoses occurring within 15 years of pregnancy^[3]. The implication is straightforward: the postpartum period, especially if prediabetes is already detectable, is the highest-yield moment to intervene.

Lifestyle intervention is the standard recommendation after GDM, but adherence is variable and the effect size, while real, does not eliminate risk for many women. GLP-1 receptor agonists have demonstrated both glycaemic and weight-related benefits in people with prediabetes in other contexts, which is the biological rationale the SERENA team is testing.

What SERENA is testing

SERENA is a double-blind, randomised, placebo-controlled trial running across 13 hospitals in Belgium. It is enrolling 252 women who had GDM and who have detectable prediabetes in the postpartum period. Participants are allocated 1:1 to once-weekly subcutaneous semaglutide 1 mg or matching placebo, on top of a standardised lifestyle intervention, for up to 160 weeks (approximately three years), with a total follow-up period of 184 weeks^[1]. Randomisation is stratified by BMI category to ensure balance across the arms.

The primary outcome is development of type 2 diabetes as defined by American Diabetes Association criteria. Secondary outcomes include weight loss, insulin sensitivity, beta-cell function, cardiometabolic risk profile, patient-reported outcomes, and cost-effectiveness. The trial also captures regression to normoglycaemia, which matters because returning to normal glucose tolerance is a meaningful clinical result even short of full diabetes prevention.

Recruitment began in September 2023 and the trial is registered under NCT05569772. The protocol paper, led by Yana Vanlaer and Katrien Benhalima of KU Leuven's Clinical and Experimental Endocrinology unit, was published to establish methodological transparency before results are available.

What this is not

SERENA is a trial protocol publication, not a results paper. There are no efficacy or safety outcomes from the intervention yet. Semaglutide is not approved by the EMA or any other regulator for diabetes prevention; the authorised indications for semaglutide remain type 2 diabetes treatment (Ozempic, Rybelsus) and chronic weight management (Wegovy)^[4]. Use outside those indications is off-label and requires prescriber judgment.

The 1 mg dose used in SERENA is the highest dose in the Ozempic type-2 diabetes label. It is lower than the 2.4 mg dose used in the Wegovy weight-management label. Whether the dose selected is optimal for this population is one of the questions the trial itself cannot yet answer.

What we do not yet know

Several important questions sit outside the scope of the protocol. First, whether the effect, if positive, will be durable after treatment stops: the STEP-4 discontinuation trial showed substantial weight regain when semaglutide was withdrawn in the obesity setting, and a parallel glucose-maintenance question exists here. Second, how results will generalise beyond the Belgian hospital setting, where lifestyle support is standardised and BMI-stratified randomisation is controlled. Third, how cost-effectiveness will compare to extended lifestyle programmes alone, given that the trial includes health economic modelling as a secondary endpoint but the answer depends on trial results.

There is also a gap in the broader prevention literature. Trials like the Diabetes Prevention Program established that intensive lifestyle intervention reduces GDM-to-T2D progression, but no large-scale GLP-1 prevention trial has reported results in this specific population (postpartum women with GDM-linked prediabetes). SERENA is designed to fill that gap.

Where this lands

SERENA is a methodologically sound protocol targeting a high-risk population at a clinically plausible intervention point. If the trial reads out positively, it would be the first randomised evidence that a GLP-1 agonist can prevent type 2 diabetes specifically in women with GDM-linked postpartum prediabetes, an indication that does not currently exist in any regulatory framework. Follow-up on our semaglutide overview for regulatory context, and check back when results from NCT05569772 are published.