GLP1s may lower 10-year risk for major adverse outcomes in chronic liver disease, diabetes
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Key takeaways:
- The 10-year risk for major adverse liver outcomes was 13.3% among initiators vs. 14.6% among non-initiators in the intention-to-treat analysis.
- The corresponding per-protocol risk was 7.4% vs. 14.4%.
Adherence to treatment with glucagon-like peptide-1 receptor agonists may lower the long-term risk for major adverse liver outcomes among patients with chronic liver disease and type 2 diabetes, according to data in Gut.
“Although achieving surrogate histopathological endpoints is considered by regulatory agencies to likely translate to improved prognosis, robust evidence is needed to understand if GLP1 agonists reduce the risk of long-term clinical outcomes, such as liver decompensation or HCC,” Axel Wester, MD, PhD, assistant professor of medicine at Karolinska Institute, and colleagues wrote.
Wester continued, “Given that the metabolic syndrome is a major driver of liver-related outcomes both in patients with MASLD and other chronic liver diseases such as alcohol-related liver disease or viral hepatitis C, there could be a similar effect of GLP1 agonists in patients with chronic liver diseases of any etiology with concomitant metabolic traits, such as type 2 diabetes.”
Using data from the Decoding the Epidemiology of LIVER disease Swedish cohort, researchers aimed to determine the long-term risk for major adverse liver outcomes (MALO) among patients with chronic liver disease and type 2 diabetes who either initiated (n = 1,026) or did not initiate (n = 15,633) GLP1 agonists.
Researchers defined MALO as decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or related death and compared parametric estimates of 10-year risk among initiators vs. non-initiators.
At baseline, most initiators began treatment with liraglutide (61.9%), followed by semaglutide (22.5%), dulaglutide (11.7%), exenatide (2.4%) and lixisenatide (1.5%). Initiators and non-initiators were monitored for a median of 64 and 76 months, respectively, in the intention-to-treat analysis and for 43 and 76 months in the per-protocol analysis.
Results of the intention-to-treat analysis showed the 10-year risk for MALO was 13.3% among initiators vs. 14.6% among non-initiators (RR = 0.91; 95% CI, 0.5-1.32), which corresponded to 7.4% vs. 14.4% in the per-protocol analysis (RR = 0.51; 95% CI, 0.14-0.88).
Further, per-protocol risk estimates were 5.4% vs. 9% (RR = 0.6; 95% CI, 0.29-0.9) at 6 years and 7.2% vs. 11.7% (RR = 0.61; 95% CI, 0.21-1.01) at 8 years.
“The risk of MALO in patients with chronic liver diseases and type 2 diabetes was lower if they initiated a GLP1 agonist and adhered to this treatment over time,” Wester and colleagues wrote. “The data were, however, not compatible with a protective intention-to-treat effect.”
They concluded: “Randomized trials using MALO as an outcome might be unfeasible, motivating further large observational studies using appropriate methodology to further delineate the effect of GLP1 agonists on the risk of MALO, complementing future phase 3 trials of GLP1 agonists.”
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