Home Medizin Können GLP-1-Agonisten das Risiko einer schweren Lebererkrankung verringern?

Können GLP-1-Agonisten das Risiko einer schweren Lebererkrankung verringern?

von NFI Redaktion

New research suggests that treatment with glucagon-like peptide-1 (GLP-1) receptor agonists may reduce the risk of developing liver cirrhosis, liver cancer, and other adverse liver outcomes in adults with type 2 diabetes and chronic liver disease.

Using an emulated target study design, researchers observed a 49% lower 10-year risk of serious liver damage (MALO) in patients with chronic liver disease and type 2 diabetes who started treatment with a GLP-1 agonist and adhered to the treatment compared to those who did not initiate GLP-1 therapy.

„Our findings support the hypothesis that GLP-1 agonists could be a treatment option to reduce the risk of MALO in this patient population,“ said lead author Axel Wester, MD, PhD, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden, in an interview with Medical News from Medscape.

„Randomized studies have only evaluated histological results (surrogate markers for liver outcomes), but in our study, we were able to examine hard clinical outcomes, which is a strength. However, it is difficult to draw definitive conclusions from a single study,“ cautioned Wester.

The study was published online in Gut.

Mixed Results

Researchers emulated a nationwide target study to estimate the long-term effects of GLP-1 agonist therapy on MALO in adult patients with chronic liver disease and type 2 diabetes, using observational data from Swedish health registries from 2010 to 2020. They included 1026 GLP-1 initiators and 15,633 non-initiators.

In the intention-to-treat analysis, the 10-year risk of MALO was 13.3% in initiators compared to 14.6% in non-initiators (risk ratio [RR] 0.91). These estimates were deemed „imprecise,“ with a 95% CI for the RR between 0.50 and 1.32, the authors noted.

In the corresponding per-protocol analysis, the risk of MALO after 10 years was 7.4% and 14.4%, corresponding to an RR of 0.51. The per-protocol risk estimates after 6 years were 5.4% and 9% (RR: 0.60) and after 8 years were 7.2% and 11.7% (RR: 0.61).

Wester and colleagues noted that their results did not demonstrate a protective effect of GLP-1 agonists in the subgroup with compensated cirrhosis – consistent with a recent Phase 2 study in patients with metabolic dysfunction-associated steatohepatitis (MASH)-related compensated cirrhosis reported by Medical News from Medscape.

A limitation of the study is the lack of data on fibrosis stage beyond classifying patients as cirrhotic (F4) or non-cirrhotic (F0-F3). The researchers also did not have access to laboratory data such as glycated hemoglobin to assess the severity of diabetes and the need for escalation to second-line treatment with GLP-1 agonists.

Promising, but Preliminary

Currently, there are no approved medications in the United States for metabolic dysfunction-associated steatotic liver disease (MASLD), so GLP-1 agonists represent „a promising class of drugs,“ said Jamile Wakim-Fleming, MD, who heads the Center for Metabolic Steatosis at the Cleveland Clinic, Cleveland, Ohio, in an interview with Medical News from Medscape.

While the results in comparing MALO between groups „were positive in GLP-1 receptor agonist initiators,“ these drugs were not protective in the intention-to-treat analysis, leading me to believe that longitudinal randomized controlled trials are needed to make a definitive conclusion regarding adverse liver-related outcomes in individuals taking GLP-1 receptor agonists,“ said Wakim-Fleming, who was not involved in the current study.

Phase 2 studies suggest that GLP-1 agonists resolve MASH in patients with MASLD, but do not cause fibrosis regression, she noted.

„Large Phase 3 studies aiming to assess the effect of GLP-1 agonists on resolution of MASH or reduction of liver fibrosis, cirrhosis, and their complications are underway,“ Wakim-Fleming said.

In addition to Phase 3 trials, large observational studies with appropriate methodology could further delineate the effect of GLP-1 agonists on the risk of MALO, the study authors write.

The study had no commercial funding. Wester and Wakim-Fleming did not disclose any relevant relationships.

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