Adults who experienced a suboptimal clinical response following metabolic and bariatric surgery achieved significant additional weight loss, improved metabolic outcomes and enhanced quality of life with semaglutide, according to a recent study.

Led by researchers at University College London (UCL), University College London Hospitals and Homerton University Hospital, the BARI-STEP trial evaluated the efficacy and safety of semaglutide 2.4 mg once weekly in patients who had undergone Roux-en-Y gastric bypass or sleeve gastrectomy at least one year previously but had lost less than 20% of their body weight after surgery.

While previous studies have shown benefits of liraglutide in this group, BARI-STEP is the first randomised controlled trial of semaglutide in patients following bariatric surgery.

The double-blind, randomised, placebo-controlled trial, published in the journal Nature Medicine, enrolled 70 adults between November 2022 and April 2025, 55 of whom (78.6%) had undergone sleeve gastrectomy and 15 (21.4%) gastric bypass.

Participants had a mean age of 47.3 years, 82.9% were female and the mean body mass index (BMI) at enrolment was 41.5.

Participants were randomly assigned to semaglutide 2.4 mg once weekly (n=35) or placebo (n=35), alongside lifestyle intervention incorporating a 500 kcal daily energy deficit and increased physical activity. The intention-to-treat analysis included 63 participants.

Efficacy and safety of semaglutide after bariatric surgery

After 68 weeks, participants receiving semaglutide achieved a mean weight loss of 18.0%, compared with a 0.4% weight gain in the placebo group. The adjusted treatment difference in percentage body weight change was −19.18% (95% CI −23.4 to −14.8; P<0.001).

Mean total body weight decreased by 21.1 kg in the semaglutide arm compared with a 0.7 kg increase with placebo. Furthermore, 85.3% of semaglutide-treated participants achieved at least 10% weight loss, 61.8% achieved at least 15% weight loss and 47.1% achieved at least 20% weight loss, compared with 6.9%, 6.9% and 3.4%, respectively, in the placebo group.

Semaglutide was also associated with significant improvements in BMI, fat mass, HbA1c, total cholesterol and triglycerides. Quality-of-life measures improved, with significant gains in overall Impact of Weight on Quality of Life-Lite scores, physical function, self-esteem and work-related domains. Baseline meal-stimulated GLP-1 responses were not associated with treatment-related weight loss, the authors said.

The safety profile was consistent with previous semaglutide studies. Gastrointestinal adverse events were common, with nausea and decreased appetite reported more frequently in the semaglutide group.

There were 12 serious adverse events recorded across the trial, including one suspected unexpected serious adverse reaction related to restrictive eating behaviour in a participant receiving semaglutide. All affected participants recovered and there were no treatment-related deaths.

Study limitations and future directions

The authors noted several limitations, including the relatively small sample size, the predominance of female participants and the low number of participants with type 2 diabetes, which limited subgroup analyses.

However, they concluded that semaglutide 2.4 mg represented a safe and effective treatment option for individuals with a suboptimal clinical response after bariatric surgery.

Further studies are now needed to investigate the mechanisms underlying treatment response and to determine whether efficacy differs between patients with suboptimal initial weight loss and those who subsequently experience weight regain, they added.

Lead investigator Dr Janine Makaronidis, consultant in diabetes and metabolism at Barts Health NHS Trust, bariatric physician at Homerton University Hospital and senior researcher at UCL, said: ‘These findings strengthen the case for using semaglutide in people who do not respond well to bariatric surgery, offering an alternative to repeat operations. They also suggest that combining surgery with weight-loss medicines is an important approach to treating severe obesity.

‘As next steps, we need larger and longer studies involving more diverse groups of patients. We would also like to investigate whether semaglutide could help patients before surgery as well as afterwards.’

Another recent study has revealed that the triple hormone receptor agonist retatrutide yields weight loss results similar to bariatric surgery.

Weight-loss drugs and health inequalities

Despite this and additional reported benefits of GLP-1s transforming obesity management, separate insights from UCL and the University of Cambridge, have highlighted that incretin-based therapies risk widening health inequalities.

Also published in Nature Medicine, the correspondence notes that access to nutrition advice, affordable healthy food, and ongoing healthcare support is likely to influence whether patients can use these drugs safely and sustain health improvements over the long term.

Senior author Dr Adrian Brown, associate professor (principal research fellow) in nutrition and dietetics in the Centre of Obesity Research at UCL, said: ‘We have highlighted that obesity treatment is not just a medical issue, but a social and structural one. Without integrated dietary support and attention to food affordability, these medications could deepen existing health inequalities.

‘The key message is clear: these treatments are powerful, but their long-term public health impact will depend on whether the right support systems are in place to ensure equitable and safe access for all patients.’

This comes as a new semaglutide 7.2mg single-dose pen has been launched by Novo Nordisk as a maintenance dose for adults with obesity, following approval from the Medicines and Healthcare products Regulatory Agency.

Previously, those who needed a 7.2mg dose of semaglutide had to be given three 2.4mg injections – taken together once a week. The new pen enables this to be done in a single injection.