Comparative Outcomes of GLP-1 Therapy vs. Bariatric Surgery in Patients with Cirrhosis

Both GLP-1 receptor agonists and bariatric surgery are increasingly used for obesity management in patients with chronic liver disease (CLD). Their comparative long-term hepatic outcomes remain unclear. We aimed to evaluate the risks of primary liver cancer, hepatic decompensation, and all-cause mortality between GLP-1-treated patients and those with prior bariatric surgery.

Using the TriNetX U.S. Collaborative Network, we identified adults above the age of 18 with obesity and underlying cirrhosis who either received GLP-1 analogues or had a history of bariatric surgery. The index event was defined as the first instance of having cirrhosis, obesity, and getting either bariatric surgery or GLP-1. Outcomes were assessed ≥ 30 days after index. Propensity score matching (PSM) (1:1) across 22 demographic, clinical, medication, and laboratory variables was done. Kaplan-Meier survival analyses were performed for primary liver cancer, hepatic decompensation, and mortality, with hazard ratios (aHRs) and 95% CIs.

After PSM, 14,240 patients were included in each cohort. Primary liver cancer occurred more frequently in GLP-1 users (3.9% vs. 3.4%, aHR 1.36, 95% CI 1.20-1.54; p < 0.001). All-cause mortality was lower with GLP-1 therapy (8.1% vs. 16.2%, aHR 0.70, 95% CI 0.65-0.75; p < 0.001). Hepatic decompensation was also lower in GLP-1 users (aHR 0.74, 95% CI 0.70-0.78; p < 0.001). Subgroup analyses based on sex revealed that among men, GLP-1 therapy was associated with lower mortality (aHR 0.76, 95% CI 0.67-0.85; p < 0.001) and fewer decompensation events (aHR 0.78, 95% CI 0.72-0.85; p < 0.001), though primary liver cancer incidence was higher. Among women, GLP-1 therapy similarly reduced mortality (aHR 0.68, 95% CI 0.62-0.75; p < 0.001) and decompensation (aHR 0.74, 95% CI 0.69-0.78; p < 0.001), with a small increase in primary liver cancer (aHR 1.30, 95% CI 1.10-1.54; p = 0.002). In patients 18-45 years, GLP-1 therapy was associated with significantly lower mortality (aHR 0.50) and reduced hepatic decompensation (aHR 0.72), with no difference in primary liver cancer risk. In patients older than 45 years, GLP-1 users likewise demonstrated lower mortality (aHR 0.69) and decompensation (aHR 0.78), although primary liver cancer incidence was modestly higher (aHR 1.28).

In patients with obesity and cirrhosis, GLP-1 therapy was associated with substantially lower mortality and hepatic decompensation compared with bariatric surgery across sex and age groups, with consistent benefit in both younger and older adults. The primary liver cancer incidence was slightly higher in GLP-1 users, especially in older adults.