Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2025 Jan 17;74(2):284-294.
doi: 10.1136/gutjnl-2024-332687.

Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease

Sungho Bea #  1   2 , Hwa Yeon Ko #  2 , Jae Hyun Bae  3 , Young Min Cho  4 , Yoosoo Chang  5 , Seungho Ryu  6 , Christopher D Byrne  7 , Ju-Young Shin  8
Affiliations
Comparative Study

Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease

Sungho Bea et al. Gut. .

Abstract

Objective: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Design: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs.

Results: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69)).

Conclusions: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA.

Keywords: DIABETES MELLITUS; FATTY LIVER.

PubMed Disclaimer

Conflict of interest statement

Competing interests: J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, UCB, SK bioscience and Pfizer, outside the submitted work.

Figures

Figure 1
Figure 1. Hepatic decompensation events in 1:1 propensity score-matched initiators of (A) SGLT-2i versus GLP-1RA and (B) SGLT-2i versus TZD. GLP-1RA, glucagon-like peptide-1 receptor agonist; IR, incidence rate; PY, person-year; RD, rate difference; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; TZD, thiazolidinedione.
Figure 2
Figure 2. Cumulative incidence of hepatic decompensation events in 1:1 propensity score-matched initiators of (A) SGLT-2i versus GLP-1RA and (B) SGLT-2i versus TZD. GLP-1RA, glucagon-like peptide-1 receptor agonist; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; TZD, thiazolidinedione.
Figure 3
Figure 3. Results of subgroup analyses for hepatic decompensation events in 1:1 propensity score-matched initiators of (A) SGLT-2i versus GLP-1RA and (B) SGLT-2i versus TZD. GLP-1RA, glucagon-like peptide-1 receptor agonist; SGLT-2i, sodium-glucose cotransporter-2 inhibitor; TZD, thiazolidinedione.
See this image and copyright information in PMC

References

    1. Stefan N, Cusi K. A global view of the interplay between non-alcoholic fatty liver disease and diabetes. Lancet Diabetes Endocrinol. 2022;10:284–96. doi: 10.1016/S2213-8587(22)00003-1. - DOI - PubMed
    1. Targher G, Corey KE, Byrne CD, et al. The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments. Nat Rev Gastroenterol Hepatol. 2021;18:599–612. doi: 10.1038/s41575-021-00448-y. - DOI - PubMed
    1. Younossi ZM, Golabi P, de Avila L, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol. 2019;71:793–801. doi: 10.1016/j.jhep.2019.06.021. - DOI - PubMed
    1. Loria P, Lonardo A, Anania F. Liver and diabetes. A vicious circle. Hepatol Res. 2013;43:51–64. doi: 10.1111/j.1872-034X.2012.01031.x. - DOI - PMC - PubMed
    1. Mantovani A, Petracca G, Beatrice G, et al. Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals. Gut. 2021;70:962–9. doi: 10.1136/gutjnl-2020-322572. - DOI - PubMed

Publication types

MeSH terms

Substances