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Clinical Trial
. 2024 Apr 1;184(4):375-383.
doi: 10.1001/jamainternmed.2023.8029.

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Heejoon Jang  1 , Yeonjin Kim  2 , Dong Hyeon Lee  1 , Sae Kyung Joo  1 , Bo Kyung Koo  3 , Soo Lim  4 , Woojoo Lee  2 , Won Kim  1
Affiliations
Clinical Trial

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Heejoon Jang et al. JAMA Intern Med. .

Abstract

Importance: Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking.

Objective: To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).

Design, setting, and participants: This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD.

Exposures: Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days.

Main outcomes and measures: The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks.

Results: In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas.

Conclusions and relevance: The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr W. Kim reported personal fees from Ildong, GSK, Hanmi, Standigm, PharmaKing, KOBIOLABS, Novo Nordisk, Novo Nordisk, Olix Pharma, TSD Life Sciences; grants from Daewoong, GSK, Novartis, Pfizer, Roche, Springbank, Ildong, Dicerna, Celgene, Hanmi, Galmed, Enyo, KOBIOLABS; stock options from KOBIOLABS and Lepidyne; and founding Remedygen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Participant Inclusion and Attrition Flow Diagram
GLP-1 indicates glucagonlike peptide-1; NAFLD, nonalcoholic fatty liver disease; and T2D, type 2 diabetes. aThe 4 classes of oral antidiabetic drugs assessed were sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas. bThese drugs included amiodarone, corticosteroids, methotrexate, tamoxifen, synthetic estrogen, valproic acid, and intravenous tetracycline.
Figure 2.
Figure 2.. Weighted Cumulative Incidence Function According to Oral Antidiabetic Drug Class
Sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with greater rates of nonalcoholic fatty liver disease (NAFLD) regression compared with other oral antidiabetic drug classes. Less adverse liver-related outcomes (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) were also observed for the SGLT2 inhibitor class. DPP-4 indicates dipeptidyl peptidase-4.
See this image and copyright information in PMC

References

    1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18(4):223-238. doi:10.1038/s41575-020-00381-6 - DOI - PMC - PubMed
    1. Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin S. Nonalcoholic steatohepatitis: a review. JAMA. 2020;323(12):1175-1183. doi:10.1001/jama.2020.2298 - DOI - PubMed
    1. Cho Y, Lim SK, Joo SK, et al. . Nonalcoholic steatohepatitis is associated with a higher risk of advanced colorectal neoplasm. Liver Int. 2019;39(9):1722-1731. doi:10.1111/liv.14163 - DOI - PubMed
    1. Targher G, Corey KE, Byrne CD, Roden M. The complex link between NAFLD and type 2 diabetes mellitus—mechanisms and treatments. Nat Rev Gastroenterol Hepatol. 2021;18(9):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(4):793-801. doi:10.1016/j.jhep.2019.06.021 - DOI - PubMed

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