A recent retrospective cohort study revealed that patients with obesity treated with semaglutide had a significantly higher risk of developing gastroparesis compared with those treated with bupropion-naltrexone or sleeve gastrectomy.

In the study, published in BMJ Open Gastroenterology, investigators led by Chino Aneke-Nash analyzed data from the Merative MarketScan Research Databases, focusing on patients aged 18 to 64 years with a body mass index (BMI) of at least 30 kg/m² from January 1, 2018, to December 31, 2022.

Among the participants, 66.7% (n = 36,990) of them received semaglutide, 13.3% (n = 7,369) of them were treated with bupropion-naltrexone, and 13.7% (n = 11,101) of them underwent sleeve gastrectomy. The incidence of gastroparesis was 6.5 cases per 1,000 person-years (PY) for semaglutide compared with 2.1 cases for bupropion-naltrexone and 1.1 cases for sleeve gastrectomy. After adjusting for baseline characteristics, the risk of gastroparesis was significantly higher for semaglutide (adjusted hazard ratio [HR] = 3.33, 95% confidence interval [CI] = 2.27–4.98) compared with bupropion-naltrexone and even higher (adjusted HR = 6.14, 95% CI = 3.94–9.57) compared with sleeve gastrectomy.

The investigators also noted that the baseline prevalence of gastroparesis among excluded patients was 1.8 per 1,000 in the sleeve gastrectomy cohort, 3.2 per 1,000 in the semaglutide cohort, and 2.6 per 1,000 in the bupropion-naltrexone cohort. Average follow-up times varied: 1 year for semaglutide, 2.1 years for bupropion-naltrexone, and 2 years for sleeve gastrectomy.

In exploratory analyses, significant predictors of gastroparesis among the patients who received semaglutide included a baseline diagnosis of metabolic dysfunction–associated fatty liver disease (MAFLD) (adjusted HR = 2.11, 95% CI = 1.39–3.21), a BMI between 30 and 34 (adjusted HR = 1.93, 95% CI = 1.42–2.62), and a diagnosis of gastroesophageal reflux disease (GERD) (adjusted HR = 1.80, 95% CI = 1.09–2.97).

"Understanding these potential side effects, though rare, may help [patients] and their care teams weigh each treatment’s risks and benefits to develop a personalized regimen," the study authors said. 

The findings contributed to the growing literature on gastrointestinal side effects associated with glucagon-like peptide-1 (GLP-1) receptor agonists, particularly in populations without type 2 diabetes. The investigators concluded that the increased incidence of gastroparesis among patients receiving semaglutide compared with other obesity treatment modalities warrants further investigation.

Full disclosure can be found in the study.