Association of Glucagon-like peptide-1 Receptor Agonists with Serious Liver Events: Scandinavian Cohort Study

Friday, August 26, 2022

2:45 PM – 3:00 PM CEST

Location: Congress Hall D2

Publication Number: 42

Background: Patients with type 2 diabetes experience an increased risk of non-alcoholic fatty liver disease (NAFLD) and subsequent complications including liver cirrhosis and hepatocellular carcinoma (HCC). Clinical trials suggest that glucagon-like peptide-1 (GLP-1) receptor agonists may have beneficial effects on NAFLD.

Objectives: To investigate the association between use of GLP-1 receptor agonists and risk of serious liver events in routine clinical practice.

Methods: We conducted a cohort study using data from nationwide registers in Denmark, Norway and Sweden, 2013- 2018. Patients aged 35-84 who were newly prescribed a GLP-1 receptor agonist or an active comparator, dipeptidyl peptidase 4 (DPP4) inhibitor, were included. The primary outcome was serious liver events; a composite of liver cirrhosis, hepatocellular carcinoma and death from hepatic causes. Secondary outcomes were the individual components of the primary outcome. In intention-to-treat analyses, Cox regression was used to estimate hazard ratios (HRs), using standardized mortality ratio weighting based on a propensity score to control for confounding.

Results: The cohort included 68510 new users of GLP-1 receptor agonists and 222906 new users of DPP4 inhibitors. Mean age of the study population was 62 years and 41% were female. The median (IQR) follow-up time was 4.1 (1.7-7.1) years for users of GLP-1 receptor agonists and 4.3 (2.0-7.2) years for users of DPP4 inhibitors. New users of GLP-1 receptor agonists had 465 serious liver events (adjusted incidence rate 1.54 events per 1000 person-years), compared with 1568 events among new users of DPP4 inhibitors (1.71 events per 1000 person-years). The adjusted hazard ratio (aHR) was 0.91 (95% CI 0.79 to 1.04) and the rate difference (RD) -0.2 (-0.4 to 0.1) per 1000 person-years. In secondary outcome analyses, use of GLP-1 receptor agonists was associated with a significantly higher risk of hepatocellular carcinoma (aHR 1.45 [1.08 to 1.94]; RD 0.1 [0.02 to 0.19]) but no statistically significant differences were found for risk of liver cirrhosis (aHR 0.88 [0.76 to 1.02]; RD -0.19 [-0.41 to 0.03]) or death from hepatic causes (aHR 0.61 [0.33 to 1.14]; RD -0.05 [-0.11 to 0.02]). The estimates were robust in several sensitivity analyses.

Conclusions: In this large Scandinavian cohort of patients seen in routine clinical practice, use of GLP-1 receptor agonists versus DPP4 inhibitors was associated with possible lower risks of liver cirrhosis as well as death from hepatic causes, although the associations were not statistically significant. The risk of hepatocellular carcinoma was significantly increased with GLP-1 receptor agonists, although the absolute risk was small.

Presenting Author(s)

Arvid Engstr�m

Karolinska Institutet
Stockholm, Stockholms l�n, Sweden

Slides

Co-Author(s)

Victor Wintzell

Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm
Stockholm, Sweden
MM

Mads Melbye

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, Denmark
HS

Henrik Svanström

Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, Sweden
BE

Björn Eliasson

Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden, Sweden
SG

Soffia Gudbjörnsdottir

Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden, Sweden
KH

Kristian Hveem

HUNT Research Center, Faculty of Medicine, NTNU—Norwegian University of Science and Technology, Levanger, Norway, Norway
CJ

Christian Jonasson

HUNT Research Center, Faculty of Medicine, NTNU—Norwegian University of Science and Technology, Levanger, Norway, Norway
AH

Anders Hviid

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark, Denmark
BP

Björn Pasternak

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Sweden
PU

Peter Ueda

Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, Sweden