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Cited by 98Diabetes Treatment and ManagementLiver Disease and TransplantationHeart Failure Treatment and Management

Glucagon-like peptide-1 receptor agonists and hepatic decompensation events in patients with cirrhosis and diabetes

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Simon, Tracey G., Patorno, Elisabetta, Schneeweiss, Sebastian·2022·Clinical Gastroenterology and Hepatology
DOI 10.1016/j.cgh.2021.07.010PMC PMC8743301
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Abstract

Background & aims The study sought to compare the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in reducing decompensation events, among patients with cirrhosis and type 2 diabetes.Methods This population-based, retrospective cohort study included patients with type 2 diabetes and cirrhosis, in a commercial healthcare database (IBM MarketScan). We constructed 3 pairwise, 1:1 propensity score (PS)-matched cohorts of adults initiating GLP-1RAs or a comparator medication (ie, DPP-4 inhibitors [2006-2020], sulfonylurea [2005-2020], or SGLT-2 inhibitors [2013-2020]). Patients were followed in an as-treated approach for decompensation events (ie, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, or esophageal variceal hemorrhage). Within each PS-matched cohort, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), controlling for >90 baseline characteristics.Results Over 132 days of median follow-up (interquartile range, 73-290 days), PS-matched rates of any decompensation were significantly lower among GLP-1RA initiators, versus DPP-4 inhibitor initiators (105.2 vs 144.0 per 1000 person-years [PY]; HR, 0.68; 95% CI, 0.53-0.88; n = 1431 pairs), and versus sulfonylureas (97.3 vs 144.0 per 1000 PY; HR, 0.64; 95% CI, 0.48-0.84; n = 1246 pairs). Similar, inverse associations were found for individual decompensation events, including ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome (HR, 0.66; 95% CI, 0.45-0.97; and HR, 0.66; 95% CI, 0.46-0.94, respectively); esophageal variceal hemorrhage (HR, 0.62 [95% CI, 0.41-0.92; and HR, 0.59; 95% CI, 0.37-0.92, respectively); and hepatic encephalopathy (HR, 0.76; 95% CI, 0.55-1.06; and HR, 0.60; 95% CI, 0.39-0.92, respectively). Results persisted in subgroups of patients with and without previously decompensated cirrhosis. In contrast, decompensation rates were similar when GLP-1RAs and SGLT-2 inhibitors were directly compared (103.5 vs 112.8 per 1000 PY; HR, 0.89; 95% CI, 0.62-1.28).Conclusions Among cirrhotic patients with type 2 diabetes, we find high rates of decompensation, consistent with previous reports; these rates were substantially lower among GLP-1RA initiators compared with DPP-4 inhibitors or sulfonylureas.

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  • Case-control studies have suggested that exposure to GLP1RAs or SGLT2 inhibitors in people with T2D is associated with a reduction in liver-related outcomes.

    “Case-control studies have suggested that exposure to GLP1RAs or SGLT2 inhibitors in people with T2D is associated with a reduction in liver-related outcomes 409,410”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [409]

    The Discussion reports lower hepatic decompensation rates with GLP-1RAs and suggests possible hepatoprotective benefits from SGLT2 inhibitors. But the Methods describe a retrospective cohort study—not a case-control study—and the findings concern people with both type 2 diabetes and cirrhosis, not people with type 2 diabetes generally. (LLM, conf=0.88)

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  1. [34]Patorno E, Pawar A, Franklin JM, Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care. Circulation 2019; 139(25): 2822– 30. doi: 10.1161/CIRCULATIONAHA.n8.039177 [ published Online First: 2019/04/09] 30955357 PMC6594384 · DOI

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Authors
Simon, T. G., Patorno, E., & Schneeweiss, S.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Simon, Tracey G.
ORCID
Venue
Clinical Gastroenterology and Hepatology
Publisher
Elsevier BV
Published
2022-06
Volume
20
Issue
6
Pages
1382-1393.e19
ISSN
1542-3565 (ISSN-L)
DOI
10.1016/j.cgh.2021.07.010
PMC
PMC8743301
OpenAlex
W3178974444
Cited by
98
References
35
Citations by year
2026: 18 · 2025: 29 · 2024: 22 · 2023: 19 · 2022: 8 · 2021: 2
FWCI
9.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Gastroenterology and Hepatology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Harvard University Center for AIDS Research
  • Dana-Farber/Harvard Cancer Center
  • National Institutes of Health (K23 DK122104)
  • National Institute on Aging (K08AG055670)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords
GLP-1 receptor agonists, liver cirrhosis, type 2 diabetes, hepatic decompensation, DPP-4 inhibitors, sulfonylureas, SGLT2 inhibitors, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, esophageal variceal bleeding, antidiabetic drug comparison
MeSH terms
Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Ascites, Diabetes Mellitus, Type 2, Esophageal and Gastric Varices, Female, Gastrointestinal Hemorrhage, Hepatic Encephalopathy, Hepatorenal Syndrome, Humans, Liver Cirrhosis, Male, Peritonitis, Retrospective Studies, Dipeptidyl-Peptidase IV Inhibitors

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