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. 2024 Apr 5;73(5):835-843.
doi: 10.1136/gutjnl-2023-330962.

Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes

Axel Wester  1 , Ying Shang  2 , Emilie Toresson Grip  2   3 , Anthony A Matthews  4 , Hannes Hagström  2   5
Affiliations

Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes

Axel Wester et al. Gut. .

Abstract

Objective: Phase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists on the risk of major adverse liver outcomes (MALO) in patients with any chronic liver disease and type 2 diabetes.

Design: We used observational data from Swedish healthcare registers 2010-2020 to emulate a target trial of GLP1 agonists in eligible patients with chronic liver disease and type 2 diabetes. We used an inverse-probability weighted marginal structural model to compare parametric estimates of 10-year MALO risk (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or MALO-related death) in initiators of GLP1 agonists with non-initiators. We randomly sampled 5% of the non-initiators to increase computational efficiency.

Results: GLP1 agonist initiators had a 10-year risk of MALO at 13.3% (42/1026) vs 14.6% in non-initiators (1079/15 633) in intention-to-treat analysis (risk ratio (RR)=0.91, 95% CI=0.50 to 1.32). The corresponding 10-year per-protocol risk estimates were 7.4% (22/1026) and 14.4% (1079/15 633), respectively (RR=0.51, 95% CI=0.14 to 0.88). The per-protocol risk estimates at 6 years were 5.4% (21/1026) vs 9.0% (933/15 633) (RR=0.60, 95% CI=0.29 to 0.90) and at 8 years 7.2% (22/1026) vs 11.7% (1036/15 633) (RR=0.61, 95% CI=0.21 to 1.01).

Conclusion: In patients with chronic liver disease and type 2 diabetes who adhered to therapy over time, GLP1 agonists may result in lower risk of MALO. This suggests that GLP1 agonists are promising agents to reduce risk of chronic liver disease progression in patients with concurrent type 2 diabetes, although this needs to be corroborated in randomised trials.

Keywords: CIRRHOSIS; DIABETES MELLITUS; EPIDEMIOLOGY; FATTY LIVER; PHARMACOTHERAPY.

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Conflict of interest statement

Competing interests: HH: institution has received research grants from Astra Zeneca, EchoSens, Gilead, Intercept, MSD, Novo Nordisk and Pfizer, all outside the current study. The other authors declare no conflicts.

Figures

Figure 1
Figure 1
Flow chart of the study population. Numbers represent study participants (initiators or non-initiators), while numbers in parentheses represent the corresponding number of unique patients. Note that the numbers of excluded study participants represent the total number of times that unique patients were non-eligible for any of the emulated target trials. If somebody was non-eligible for all the 131 emulated target trials, they would contribute with an addition of 131 to this total number.
Figure 2
Figure 2
Inverse-probability weighted risk curves of major adverse liver outcomes comparing initiators of glucagon-like peptide-1 receptor (GLP1) agonists with non-initiators. (A) intention-to-treat effect, (B) per-protocol effect.
See this image and copyright information in PMC

Comment in

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