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For people with obesity and diabetes, bariatric metabolic surgery was associated with a greater reduction in mortality compared with first-generation GLP-1 receptor agonists if the individuals had their diabetes for a decade or less, according to an observational, retrospective cohort study from Israel.

Over a median follow-up of 6.8 years, bariatric surgery among patients with this shorter diabetes duration was associated with a 62% reduction in mortality compared with GLP-1 agonists (HR 0.38, 95% CI 0.25-0.58), reported Orna Reges, PhD, of Ariel University in Israel, and colleagues.

This link became non-significant when accounting for maximal change in body mass index (BMI), however (HR 0.79, 95% CI 0.43-1.48).

"The fact that the survival advantage disappeared after adjusting for maximal weight loss during follow-up suggests that the association between treatment type and all-cause mortality is mediated by the amount of weight loss," the authors wrote in .

As for those with a diabetes duration longer than 10 years, about a fifth of the study cohort, bariatric surgery did not yield a survival advantage compared with GLP-1 receptor agonists (HR 0.65, 95% CI 0.39-1.08), despite a long-term decrease in BMI that was greater than with GLP-1 agonists (-21.9% vs -7.2% change from baseline).

"This finding may be explained by the adverse effects of prolonged diabetes duration, which masked the benefit associated with weight reduction," the researchers explained. "This result is in line with reports of greater prevention of diabetes complications after BMS [bariatric metabolic surgery] among individuals with a shorter duration of diabetes."

Other factors like aging and the smaller sample size of patients with a long diabetes duration could have played a role in this null association, they added.

Neither treatment significantly reduced the risk for nonfatal major adverse cardiovascular events, including myocardial infarction, stroke, and ischemic heart disease:

• Diabetes duration of ≤10 years: HR 0.74 (95% CI 0.49-1.10)
• Diabetes duration over 10 years: HR 1.21 (95% CI 0.80-1.85)

Of note, the analysis only included first-generation GLP-1 agonists: liraglutide (Victoza; 61.9%), dulaglutide (Trulicity; 21.2%), exenatide (Byetta, Bydureon; 13.6%), lixisenatide (1.4%), insulin degludec and liraglutide (1.6%), or insulin degludec and lixisenatide (0.3%). The study did not include newer agents such as semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound), which are known for their more substantial weight-loss effects.

Reges and colleagues used electronic health record data from Clalit Health Services, the largest healthcare organization in Israel, and included 6,070 members ages 24 and older with diabetes diagnosed after age 21. All had a BMI of 30 or greater. They underwent bariatric surgery or received GLP-1 receptor agonists from January 2008 through December 2021, and were matched 1:1 by age, sex, and clinical characteristics

Mean age was 51, and 64.9% were women. Most had hyperlipidemia and/or hypertension at baseline. Mean Hba1c levels were significantly higher at baseline in GLP-1 agonist users versus surgery patients (9.1% vs 7.5%). Some exclusion criteria included cancer diagnosis in the 2 years prior, end-stage kidney disease, pregnancy, and a history of ischemic heart disease, ischemic stroke, or congestive heart failure.

Bariatric surgeries included laparoscopic banding (12.4%), Roux-en-Y gastric bypass (46.4%), and laparoscopic sleeve gastrectomy (41.2%). GLP-1 agonists were taken for at least 6 months within a period of 12 consecutive months.

Models were adjusted for diabetes duration; age; ethnicity; BMI; HbA1c level; socioeconomic status; diagnosis of atrial fibrillation, hyperlipidemia, and hypertension; smoking status; and use of renin-angiotensin system agents, lipid-modifying agents, insulin, SGLT2 inhibitors, and other blood glucose-lowering drugs.

Individual types of bariatric surgery weren't compared with types of GLP-1 receptor agonists, which was a limitation to the study, Reges and team noted. Furthermore, patients who switched between the treatments were excluded, but initiation of GLP-1 agonists after bariatric surgery could be a signal that the surgery wasn't successful.

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