GLP-1RA use linked to lower risk for cirrhosis, mortality in MASLD with diabetes
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Key takeaways:
- Glucagon-like peptide-1 receptor agonist use was associated with a lower risk for progression to cirrhosis, its complications and mortality.
- This effect was not seen in patients with existing cirrhosis.
Use of glucagon-like peptide-1 receptor agonists was associated with a reduced risk for progression to cirrhosis and other complications in patients with metabolic dysfunction-associated steatotic liver disease and diabetes, data showed.
“One candidate chemopreventive agent class is glucagon-like peptide 1 receptor agonists (GLP-1RAs), currently used to treat diabetes and obesity,” Fasiha Kanwal, MD, MSHS, professor and section chief of gastroenterology at Baylor College of Medicine, and colleagues wrote in JAMA Internal Medicine. “GLP-1RAs were associated with histological resolution of steatohepatitis in several randomized clinical trials. ... Patients with MASLD who have not yet developed cirrhosis represent an important population for observational studies to investigate the associations of GLP-1RAs.”
To determine whether use of GLP-1RAs is associated with lower incidence of cirrhosis and its complications in this patient population, Kanwal and colleagues conducted a retrospective study, using the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. They identified 16,058 patients with MASLD and diabetes who initiated GLP-1RAs between January 2006 and June 2022 and matched them to an equal number of patients who initiated dipeptidyl peptidase 4 inhibitors (DPP-4is) in the same month.
The primary outcome was progression to cirrhosis, with secondary outcomes of a composite of associated complications, including decompensation, hepatocellular carcinoma or liver transplant; individual complications; and all-cause mortality. Among those who already had cirrhosis, the primary outcome was a composite of complications.
At baseline, 14,606 patients on GLP-1RAs (mean age, 60.56 years; 89.1% men) did not have cirrhosis and 1,452 patients (mean age, 66.99 years; 93.7% men) had cirrhosis. The same number of patients on DPP-4is was used for analysis.
According to study results, GLP-1RA use was associated with a 14% decreased risk for cirrhosis compared with DPP-4i use (9.98 vs. 11.1 events per 1,000 person-years; HR = 0.86; 95% CI, 0.75-0.98) among patients without cirrhosis at baseline.
In addition, the risk for the composite outcome was 22% lower with GLP-1RA use vs. DPP-4i use (1.89 vs. 2.55 events per 1,000 person-years; HR = 0.78; 95% CI, 0.59-1.04), which included a 30% lower risk for decompensation (1.8 vs. 2.26 events; HR = 0.75; 95% CI, 0.55-1.01) and an 11% lower risk for all-cause mortality (21.77 vs. 24.43 events; HR = 0.89; 95% CI, 0.81-0.98). The risk for HCC was 0.24 vs. 0.27 events per 1,000 person-years (HR = 0.89; 95% CI, 0.4-2.01).
Researchers observed no statistically significant differences between user groups in the risk for cirrhosis complications (18.64 vs. 15.31 events per 1,000 person-years; HR = 1.18; 95% CI, 0.77-1.81), decompensation (14.45 vs. 13.32 events; HR = 1.14; 95% CI, 0.72-1.82), HCC (5.32 vs. 3.2 events; HR = 1.41; 95% CI, 0.69-2.9) or all-cause mortality (54.75 vs. 61.91 events; HR = 0.88; 95% CI, 0.73-1.06) among those with cirrhosis at baseline.
“In this large national cohort study of patients with MASLD and diabetes but without cirrhosis, we observed protective associations between GLP-1RA use and subsequent development of cirrhosis, cirrhosis complications and overall mortality,” Kanwal and colleagues wrote. “This chemopreventive activity became apparent 18 to 24 months after treatment initiation and increased over time.”
They continued: “These data highlight the potential consequences of delaying treatment — either by lack of access or by patient or health care professional choice — on subsequent risk of cirrhosis complications.”
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