GLP-1s post-bariatric surgery offer additional cardiovascular benefits

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may help to reduce the risk of heart attacks, strokes, and other major adverse cardiovascular events (MACE) as well as death in adults with obesity and diabetes following bariatric surgery who did not achieve sufficient weight loss and diabetes control, according to researchers from Ariel University and Clalit Health Services in Israel. The study was presented at the European Congress on Obesity 2025.

“These results represent the first phase of the study, focusing on real-life data showing that people who did not achieve sufficient weight loss and diabetes control after surgery often started GLP-1RA treatment later, which enabled them to achieve weight and blood sugar levels similar to those who had more successful surgery results said co-lead author, Professor Orna Reges from Ariel University and Clalit Health Services in Israel. "This phase also evaluated whether starting GLP-1RAs is linked to a first occurrence of major cardiovascular events (MACE). To better understand and confirm this potential link, the next phase of the study will apply a target trial emulation approach."

The observational, real-life retrospective cohort study found that in adults with obesity and type 2 diabetes but no prior heart disease, GLP-1RAs helped to improve weight-loss and diabetes control in patients that did not improve sufficiently after surgery. Treatment with GLP-1RAs was associated with a 67% lower risk of MACE or death from any cause compared to those who had bariatric surgery alone.

"These findings provide important initial clinical insights," Reges explained. "In real-life settings, people living with obesity and type 2 diabetes are at increased risk of cardiovascular disease, and these results suggest that initiating GLP-1RAs after bariatric surgery may help to achieve sustained reductions in weight and blood glucose levels - comparable to those achieved by bariatric surgery alone in other patients - and may also reduce the long-term risk for MACE."

In people with obesity and type 2 diabetes, the separate advantage of bariatric surgery and GLP-1RAs in reducing weight, glucose level, and MACE is well established. However, the benefit of GLP-1RA treatment after bariatric surgery for the primary prevention of MACE is unclear.

To address this gap, researchers analysed electronic health record data for patients (aged 24 years or older) with obesity (BMI of 30 kg/m2 or higher) and type 2 diabetes who underwent bariatric surgery alone or were treated with GLP-1RAs (semaglutide [76%] and liraglutide [13%]) following bariatric surgery between 2008 and 2018 from Clalit health services, which insures over half of the Israeli population (approximately 4.8 million patients).

In total, 822 participants (72% females; average age 58 years) with no prior history of ischemic heart disease, ischemic stroke, congestive heart failure or GLP-1RA treatment before surgery were included in the study.

Each participant treated with a GLP-1RA post-surgery was matched with another patient who underwent bariatric surgery alone, based on sex, age, BMI at the start of the study, and the number of years since surgery.

They were followed from the start of GLP-1RA treatment until the end of December 2023 to assess changes in BMI and blood glucose levels, as well as the occurrence of a first MACE or death.

During an average follow-up of around 1.7 years, 18 patients were diagnosed with a new MACE or died. The analysis found that new cases of MACE or death from any cause occurred in 13 of 411 (3.2%) surgery-only patients and in five of 411 (1.2%) patients treated with a GLP-1RA post-surgery, with GLP-1RA treatment linked to a 67% reduction in MACE or death.

The researchers also found that people who started GLP-1RA treatment after surgery had higher weight and blood sugar levels at first, but over time, both dropped and became similar to those who had only the surgery.

The researchers noted that the study is limited because of the small number of participants and further research is needed to determine if these findings are generalisable to other people.

"These findings add to the growing evidence of the cardiovascular benefits of GLP-1RAs and underscore their potential as an additional treatment option for the management of cardiovascular health for the growing number of people affected by obesity,” added co-lead author, Professor Dror Dicker from Hasharon Hospital, Rabin Medical Center, Israel. "Further large, rigorous clinical trials are needed before any firm conclusions can be drawn about the effectiveness and safety of GLP-1RA treatment after bariatric surgery, and to determine the timing for which this intervention is optimal."