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

Abstract

ImportanceSeveral 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.ObjectiveTo investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).Design, Setting, and ParticipantsThis 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.ExposuresReceiving 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 MeasuresThe 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.ResultsIn 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 RelevanceThe 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.

Correspondence on Letter regarding “Prognosis of biopsy-confirmed MASLD: A sub-analysis of the CLIONE study”

“…Recent studies have demonstrated the usefulness of the diabetes mellitus drugs sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) for treatment of MASLD. Thus, their potential as therapeutic agents is expanding [ 10 - 12 ], and in actual clinical practice, there are many MASH/MASLD patients already taking SGLT-2i and GLP-1RA. In addition, the United States Food and Drug Administration recently approved the first oral thyroid hormone receptor-beta selective agonist [ 13 ] for MASH/MASLD treatment.…”

Metabolic Dysfunction–Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options

“…As a result, although the use of metformin alone in treating subjects with liver steatosis is not convincingly supported, so far, a number of ongoing trials oriented to the management of the steatotic liver include the use of metformin together with other anti-diabetic drugs as SGLT-2 inhibitors, pioglitazone, liraglutide, gliclazide, sitagliptin [ 262 ]. In a recent Korean retrospective, nonrandomized interventional cohort study in patients with T2DM classified as NAFLD, SGLT2 inhibitors, thiazolidinediones, and DPP-4 inhibitors, each combined with metformin, have been associated with a clinical regression of NAFLD, when compared with the combination metformin- sulfonylureas [ 263 ].…”