TOPLINE

In a large real-world study of adults with obesity who underwent metabolic bariatric surgery, those who began taking a GLP-1 either before or after surgery had lower all-cause mortality than those who underwent surgery alone. Starting GLP-1 therapy after surgery was associated with fewer cardiovascular events, micronutrient deficiencies, and postoperative complications.

METHODOLOGY

• GLP-1s improve weight loss and glycemic control in patients who respond poorly to metabolic bariatric surgery alone. However, the optimal time to start these drugs — before or after surgery — remains unclear.
• Researchers conducted a retrospective cohort study using real-world data of adults with obesity who underwent metabolic bariatric surgery by comparing three approaches: starting a GLP-1 at least 1 month after surgery (requiring three or more consecutive prescriptions), starting a GLP-1 at least 3 months before surgery (requiring three or more consecutive prescriptions), and surgery alone with no GLP-1 use.
• After propensity score matching, three comparison cohorts were created: GLP-1 after surgery vs surgery only (n = 20,066 per group), GLP-1 before surgery vs surgery only (n = 14,330 per group), and GLP-1 after vs before surgery (n = 13,848 per group). The mean ages across the matched cohorts ranged from 46.8 to 48.4 years, and about 79.4%-81.1% of participants were women.
• The primary outcome was all-cause mortality. Secondary outcomes included a five-point major adverse cardiovascular event (MACE) composite (stroke, myocardial infarction, atrial fibrillation or flutter, cardiac arrest, and heart failure), micronutrient deficiencies, incident chronic kidney disease, osteoporosis, small bowel obstruction, internal hernia, and cholelithiasis.
• All outcomes were assessed during a follow-up period of 12 months.

TAKEAWAY

• Starting a GLP-1 after surgery reduced the risk for all-cause mortality by 88% compared with surgery alone (hazard ratio [HR], 0.12); starting GLP-1 before surgery reduced the risk by 80% (HR, 0.20; P < .001 for both).
• Postoperative initiation was also associated with a 16% lower risk for five-point MACE compared with surgery alone (HR, 0.84; P = .032); preoperative initiation showed no significant difference; cardiovascular benefits were greater with postoperative vs preoperative initiation (HR, 0.82).
• Patients who received GLP-1s after surgery had a 10% lower risk for micronutrient deficiency (HR, 0.90), whereas those who received GLP-1s prior to surgery had an 18% higher risk (HR, 1.18; P < .05 for both); the risk for deficiencies was lower for postoperative vs preoperative initiation (HR, 0.77).
• Postoperative initiation was linked to a 65% lower risk for small bowel obstruction, 41% lower risk for internal hernia, and 23% lower risk for cholelithiasis (P < .05 for all). The reductions for small bowel obstruction and cholelithiasis were significantly greater with postoperative vs preoperative initiation.

IN PRACTICE

“Overall, postoperative initiation appears to offer the most advantageous balance of short-term survival, cardiometabolic benefit, and surgical safety,” the study authors wrote.

SOURCE

The study was led by Guy Loic Nguefang, Texas Tech University Health Sciences Center, Odessa, Texas. It was published online in Obesity Surgery.

LIMITATIONS

Residual confounding could not be excluded. The study relied on administrative codes. Data on specific GLP‑1 formulations, dosing, and adherence were not available. Moreover, the long‑term durability of metabolic and cardiovascular benefits, sustained weight loss, and late complications could not be assessed. The study authors cautioned that the mortality findings are susceptible to immortal time bias because patients had to survive long enough after surgery to qualify for postoperative GLP-1 therapy, whereas the surgery-alone group was at risk from the time of surgery; the authors specifically noted that the reported 88% mortality reduction with postoperative initiation should not be taken as a reliable estimate of the true drug effect.

DISCLOSURES

The study received no specific funding, and the authors disclosed having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.