Baylor College of Medicine–led researchers came up with that result in a cohort study of 16,000 patients treated by the U.S. Veterans Health Administration (VHA) but called for confirmation of the chemopreventive benefits of GLP-1 RAs by clinical trials.
Of study participants, 1,452 had cirrhosis and 14,606 did not. The authors advised in JAMA Internal Medicine that GLP-1 RA use was associated with a statistically significant reduction in the risk of progression to cirrhosis and its complications in patients with MASLD and diabetes versus the use of an active comparator treatment.
“The chemopreventive benefit was limited to patients who initiated GLP-1 RAs earlier in the disease course; patients who started GLP-1 RAs after they had already progressed to cirrhosis did not have lower rates of progression to hepatic decompensation or hepatocellular cancer,” the researchers added.
Background information in the articles noted that MASLD is an increasing cause of cirrhosis, and GLP-1 RAs are effective in improving liver inflammation in patients with MASLD.
The current study sought to determine whether the use of GLP-1 RAs was associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.
Data for the research came from the national VHA Corporate Data Warehouse and Central Cancer Registry. The data included patients with MASLD and diabetes who were seen at 130 VHA hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022. The study team followed patients from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first.
The researchers propensity score–matched each GLP-1 RA new user in a 1:1 ratio to a patient who initiated a DPP-4i during the same month. For patients without cirrhosis, the primary outcome was designated as progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, while secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality.
Participants without cirrhosis initiating GLP-1 RAs had a mean age of 60.56 years, and 89.1% were male; those with cirrhosis had a mean age of 66.99 years, and 93.7% were male at baseline.
The results indicated that in patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs. 11.10 events per 1,000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). The researchers reported that similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs. 2.55 events per 1,000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs. 24.43 events per 1,000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis.
“The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course,” the authors emphasized.
MASLD is the fastest growing cause of cirrhosis and its complications, including HCC.
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