Study shows cardiovascular benefits of GLP-1RAs in patients following bariatric surgery

Medications like semaglutide and liraglutide may help to reduce the risk for 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 new research being presented at this year's European Congress on Obesity (ECO) in Malaga, Spain (11-14 May).

The observational, real-life retrospective cohort study found that in adults with obesity and type 2 diabetes but no prior heart disease, glucagon-like peptide-1 receptor agonists (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. In real-life settings, people living with obesity and type 2 diabetes are at increased risks 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."

Professor Orna Reges, co-lead author from Ariel University and Clalit Health Services, Israel

GLP-1RAs, taken once a week by injection, simulate naturally produced incretin hormones, which help to lower blood sugar levels after a meal, and also slow digestion, so people feel full for longer, causing them to eat less.

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 analyzed 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 5 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 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. Nevertheless, "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 Reges.

She added, "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.". According to co-lead author Professor Dror Dicker from Hasharon Hospital, Rabin Medical Center, Israel, "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. 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."