BARI-STEP: Semaglutide helps patients who do not respond to bariatric surgery

Outcomes from the BARI-STEP trial, led by Dr Janine Makaronidis at the University College London Hospitals (UCLH) Centre for Obesity Research, has concluded that the weight loss drug semaglutide helps patients who do not respond to bariatric surgery.

Janine Makaronidis

“These findings strengthen the case for using semaglutide in people who do not respond well to bariatric surgery, offering an alternative to repeat operations,” said Makaronidis. “They also suggest that combining surgery with weight-loss medicines is an important approach to treating severe obesity.”

Metabolic/bariatric surgery is a highly effective treatment for people living with severe obesity and/or metabolic health conditions, which works through changing the anatomy of the digestive system and thereby changing the way it functions and the hormones it produces. Procedures include Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG).

However, around one in five people who have bariatric surgery either do not lose enough weight or regain weight afterwards. With around 500,000 bariatric surgeries taking place around the world each year, there is a large need for alternative treatments for this group.

Previously, options for patients who responded sub-optimally to bariatric surgery were lifestyle intervention - which had limited benefit - or further surgery - which had increased surgical risk, was invasive, and was only available to a minority of patients.

BARI-STEP is a phase III b, double-blinded, randomised, parallel group trial in patients with poor weight loss following bariatric surgery. The aim of this trial was to determine whether 68 weeks of subcutaneous semaglutide 2.4 mg causes greater percentage weight loss and to estimate the extent of any reduction, reduction in adiposity, improvement in metabolic indices, physical function and health-related quality of life (HRQoL), than placebo in patients with poor weight loss following RYGB or SG.

A similar medicine, liraglutide, has previously shown some benefit in this group, but earlier research found semaglutide produced greater weight loss. BARI-STEP is the first randomised controlled trial of semaglutide in patients following bariatric surgery.

The study involved 70 patients recruited from University College London Hospitals and Homerton University Hospital. Participants took part for 68 weeks and were randomly assigned to receive either semaglutide or a placebo injection. Both groups also received lifestyle advice and support with a reduced-calorie diet.

Among patients taking semaglutide:

• 85% lost at least 10% of their body weight, compared with 7% in the placebo group

• 62% lost at least 15% of their body weight, compared with 7% in the placebo group

• 47% lost at least 20% of their body weight, compared with 3% in the placebo group

Researchers found that most of the weight loss came from body fat rather than muscle. The semaglutide group also showed improvements in blood sugar levels, cholesterol and other measures linked to heart and metabolic health. Patients also reported better quality of life. The side effects seen in the study were already well known from previous semaglutide research, including nausea and reduced appetite.

“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,” she added.

The study was supported and co-funded by the NIHR University College London Hospitals Biomedical Research Centre.

The findings were featured in the paper, ‘Semaglutide vs placebo in individuals with poor weight-loss following bariatric surgery: a double-blinded, randomised, placebo-controlled trial’, published in Nature Medicine. To access this paper (log-in maybe required), please click here