Risk of Hepatic Events Associated with Use of SGLT-2 Inhibitors Versus GLP-1RA, and Thiazolidinedione Among Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes

Wednesday, August 28, 2024

2:15 PM – 2:30 PM CEST

Location: Room II

Presenting Author(s)

HK

Hwa Yeon Ko, PharmD

PhD student
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea, Republic of Korea

Slides

Co-Author(s)

Sungho Bea, PharmD, PhD

Postdoctoral fellow
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States
YC

Young Min Cho, MD, PhD

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea, Republic of Korea
JB

Jae Hyun Bae, MD, PhD

Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea, Republic of Korea
YC

Yoosoo Chang

Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine, Seoul, South Korea, Republic of Korea
SR

Seungho Ryu

Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine, Seoul, South Korea, Republic of Korea
CB

Christopher D Byrne

National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom, United Kingdom
Ju-Young Shin, PhD

Associate Professor
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
Suwon, Republic of Korea

Background: Despite emerging evidence supporting the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with non-alcoholic fatty liver disease (NAFLD), no head-to-head comparisons with guideline-recommended glucose-lowering medications, such as glucagon-like peptide 1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD), have been undertaken.

Objectives: To examine the hepatic effectiveness of SGLT-2i through a head-to-head comparison with GLP-1RA and TZD in patients with NAFLD and type 2 diabetes (T2D).

Methods: Using health insurance claims data from South Korea, we established two pairwise 1:1 propensity score (PS)-matched cohorts who initiated SGLT-2i, GLP1-RA (cohort #1, median age=57 years, 60% male), or TZD (cohort #2, median age=57 years, 72% male) between January 2014 and December 2022. The primary outcome was a composite of hepatic decompensation events, including ascites, esophageal varices with bleeding, hepatic failure, or liver transplant. Patients were followed from the day after the initiation of cohort entry until the occurrence of a study outcome, censoring due to discontinuation (or switching) of the cohort entry-defining drug, death, or the end of the study period (31 December 2022), whichever came first. Within the 1:1 propensity score-matched cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% CIs for the risk of hepatic decompensation events associated with the use of SGLT-2i compared to guideline-recommended glucose-lowering medications. Secondary analyses examined the ingredient-specific effects of SGLT-2i and stratified on age, sex, history of cirrhosis, history of insulin use, and history of an endocrinologist visit.

Results: In cohort #1, compared to GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.92, 95% CI 0.76-1.12). In cohort #2, compared to TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (0.77, 0.72-0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: 0.86 [0.79-0.93]; female: 0.62 [0.56-0.69]), history of insulin use (insulin use: 0.66 [0.59-0.75]; no insulin use: 0.80 [0.74-0.86]), and history of an endocrinologist visit (endocrinologist visit: 0.67 [0.59-0.77]; no endocrinologist visit: 0.79 [0.74-0.86]).

Conclusions: Given the well-established connection between type 2 diabetes and liver disease, our findings provide real-world evidence endorsing the consideration of SGLT-2i as a plausible therapeutic approach for preventing hepatic deterioration among patients with NAFLD and T2D.