Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors, and Glucagon-Like Peptide-1 Receptor Agonists Among Patients with Type 2 Diabetes Varying Non-Alcoholic Fatty Liver Disease Status

Abstract

Importance: non-alcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in T2D patients with concomitant NAFLD remains uncertain.

Objective: to investigate the effectiveness of SGLT-2i and GLP-1RA among patients with type 2 diabetes varied by the presence or absence of NAFLD.

Design: retrospective, population-based, nationwide cohort study using an active-comparator new-user design.

Setting: South Korea (January 2013 to December 2020).

Participants: two distinct new-user active-comparator cohorts of patients aged 40+ years who initiated SGLT-2i or GLP-1RA and were; propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). After 1:1 PS matching, 140,438 patients were retrieved in the first cohort (mean age 57.5 [SD 10.3]; male 56.7%) and 34,886 patients were identified in the second cohort (mean age 59.5 [SD10.5]; male 51.3%.

Main outcome measures: 1) major adverse cardiovascular events (MACE), a composite endpoint of hospitalisation for myocardial infarction, hospitalisation for stroke, and cardiovascular death; and 2) hospitalisation for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HR). Wald’s test was applied to assess the effect of heterogeneity by NAFLD. Data analysis was performed from October 2022 to March 2023.

Results: compared with DPP-4i, SGLT-2i were associated with a lower risk of MACE (HR 0.78, 95%CI 0.71-0.85) and HHF (0.62, 95%CI 0.48-0.81). GLP-1RA were associated with a decreased risk of MACE (0.49, 95% CI 0.39-0.62) but demonstrated statistically insignificant findings regarding HHF (0.64, 95% CI 0.39-1.07). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE, with NAFLD: 0.73, 95%CI 0.62-0.86 vs without NAFLD: 0.81, 95%CI 0.72-0.91; HHF, with NAFLD: 0.76, 95%CI 0.49-1.17 vs without NAFLD: 0.56, 95%CI 0.40-0.78) and for GLP-1RA (MACE, with NAFLD: 0.49, 95%CI 0.32- 0.77 vs without NAFLD: 0.49, 95%CI 0.37-0.65; HHF, with NAFLD: 0.82, 95%CI 0.38-1.76 vs without NAFLD: 0.54, 95%CI 0.27-1.06).

Conclusions and relevance: in this population-based cohort study, SGLT-2i showed a decreased risk of MACE and HHF, while GLP-1RA decreased the risk of MACE among patients with T2D irrespective of baseline NAFLD status.

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Identifiers

ORCID for Chris Byrne: orcid.org/0000-0001-6322-7753

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