GLP-1RAs may offer ‘hepatoprotective’ benefit for diabetes, alcohol-related liver disease
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Key takeaways:
- GLP-1RAs may help reduce risk for adverse liver outcomes in alcohol-associated liver disease and diabetes.
- Notably, GLP-1RA use was linked to reduced likelihood of hepatic decompensation.
SAN DIEGO — Glucagon-like peptide-1 receptor agonists may help alleviate risk for adverse liver outcomes, particularly hepatic decompensation, among patients with type 2 diabetes and alcohol-associated liver disease.
“Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are primarily used for glycemic control in patients with diabetes and have recently been approved for weight loss,” Zayed Rashid, MD, a research fellow in the department of surgery at Ohio State University, told Healio. “Studies have shown that these medications may offer benefits beyond their routine indications including liver-related improvements in conditions such as metabolic-associated fatty liver disease, due to their metabolic effects.”
Coupled with metabolic benefits, Rashid noted that recent studies of patients treated with GLP-1RAs have also reported an aversion to alcohol consumption, which could enhance its potential use for alcohol use disorders.
To determine if GLP-1RAs offer “beneficial effects” for patients with alcohol-associated liver disease (ALD), Rashid and colleagues conducted a retrospective analysis of the IBM-Marketscan database, identifying 14,730 patients with type 2 diabetes who were also diagnosed with ALD (median age, 57 years; 66.2% male) between 2013 and 2020.
Comparing patients who were prescribed GLP-1RAs following their ALD diagnosis (n=312) against those who did not, the researchers used Poisson regression models to calculate the adjusted incidence of adverse liver outcomes, including hepatic decompensation, portal hypertension, hepatocellular carcinoma and the need for liver transplantation.
According to results presented at The Liver Meeting, patients who received GLP-1RAs exhibited a “lower overall incidence of adverse outcomes” compared with those who did not, Rashid noted, most notably hepatic decompensation (22.4% vs. 32.2%) and HCC (0.3% vs. 3%) (P <.001). However, GLP-1RA use did not affect risk for portal hypertension or transplantation (P >.05).
After overlap propensity score weighting, the researchers found that overall incidence of adverse liver outcomes was lower among patients who used GLP-1RAs vs. those who did not (46 events per 379 person-years vs. 75 events per 353 person-years), with an adjusted incidence rate of 0.57 (95% CI, 0.39-0.82; P =.003).
Further, patients who used GLP-1RA exhibited reduced risk for hepatic decompensation events (33 events over 400 person-years) compared with patients who did not use GLP-1RAs (57 events per 381 person-years), with a lower adjusted incident rate of 0.56 (95% CI, 0.36-0.86; P =.008). Rashid noted that in a stratified analysis, “the benefit of GLP-1RA on composite adverse liver outcomes remained consistent,” regardless of baseline liver compensation.
“GLP-1RA medications may have a hepatoprotective effect among patients with alcohol-associated liver disease,” Rashid told Healio. “As such, these medications can serve as an effective therapeutic tool among these patients. The study suggests that GLP-1RA medications may help reduce adverse liver outcomes, particularly hepatic decompensation, in patients with both alcohol-associated liver disease and type 2 diabetes.”
He added: “The current study provides evidence that GLP-1RA medications may be clinically effective among patients with alcohol-associated liver disease. However, the study only highlights an association rather than establishing causation. Nonetheless, it lays a strong foundation for future clinical trials, potentially expanding the use of GLP-1RA medications beyond diabetes management and weight control.”