GLP-1 RA Tied to Lower Cirrhosis Risk in MASLD, Diabetes

A recent study published in JAMA Internal Medicine on September 16, 2024, has revealed promising findings for patients suffering from metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes. According to the research led by Dr. Fasiha Kanwal from the Baylor College of Medicine in Houston, the use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) is linked to a lower risk of developing cirrhosis, its complications, and related mortality.

The investigation was a retrospective cohort study involving patients from 130 Veterans Health Administration hospitals and associated outpatient clinics. The study focused on individuals diagnosed with MASLD and diabetes who had initiated treatment with either GLP-1 RA or dipeptidyl peptidase 4 inhibitors (DPP-4i). To ensure a robust comparison, patients were matched using propensity scores in a 1:1 ratio based on their baseline characteristics.

A total of 16,058 patients were included in the study, with 14,606 patients not having cirrhosis and 1,452 patients already diagnosed with cirrhosis at the start of the treatment. Each group of GLP-1 RA users was matched with an equal number of individuals who had started DPP-4i therapy. The findings showed that among patients without cirrhosis, those who were treated with GLP-1 RA exhibited a significantly lower risk of developing cirrhosis compared to those using DPP-4i. Specifically, the incidence rates were 9.98 events per 1,000 person-years for GLP-1 RA users compared to 11.10 events per 1,000 person-years for DPP-4i users, corresponding to a hazard ratio (HR) of 0.86 with a 95% confidence interval (CI) ranging from 0.75 to 0.98.

In addition to the reduced risk of cirrhosis, the study also found that GLP-1 RA use was associated with a lower risk of the composite outcome of cirrhosis complications and mortality. The hazard ratios for these outcomes were 0.78 (95% CI, 0.59 to 1.04) for complications and 0.89 (95% CI, 0.81 to 0.98) for mortality when compared to DPP-4i use.

However, for patients who already had cirrhosis at the beginning of the study, GLP-1 RA use did not demonstrate any significant associations with improved outcomes. This suggests that the benefits of GLP-1 RA may be more pronounced in the early stages of liver disease progression, highlighting the importance of early intervention.

"The results of this study advocate for the necessity of long-term randomized clinical trials to further investigate the potential benefits of GLP-1 RA for the primary prevention of cirrhosis in patients with MASLD," the authors remarked.

It is noteworthy that two of the authors of the study disclosed affiliations with the biopharmaceutical industry, underscoring the importance of further independent research to validate these findings. Nevertheless, this study represents a significant step forward in understanding the potential role of GLP-1 RA in managing liver disease among diabetic patients, offering a hopeful prospect for improving patient outcomes and reducing the burden of cirrhosis.