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. 2023 Dec 1;6(12):e2349856.
doi: 10.1001/jamanetworkopen.2023.49856.

Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status

Sungho Bea  1 , Han Eol Jeong  1   2 , Kristian B Filion  3   4 , Oriana Hy Yu  4   5 , Young Min Cho  6   7 , Bon Hyang Lee  6 , Yoosoo Chang  2   8   9   10 , Christopher D Byrne  11   12 , Ju-Young Shin  1   2   10
Affiliations

Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status

Sungho Bea et al. JAMA Netw Open. .

Abstract

Importance: Nonalcoholic 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) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain.

Objective: To investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD.

Design, setting, and participants: This retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023.

Main outcomes and measures: The main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD.

Results: After 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79 633 [56.7%] male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17 894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06]).

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

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bea reported receiving grants from the Korea Health Industry Development Institute (KHIDI) outside the submitted work. Prof Yu reported serving on the advisory board of Novo Nordisk Canada outside the submitted work. Prof Shin reported receiving grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, Daiichi Sankyo, GlaxoSmithKline, Celltrion, SK Bioscience, and Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Outcomes for the 1:1 Propensity Score–Matched Cohort of New Users of Sodium Glucose Cotransporter-2 Inhibitors (SGLT-2i) and New Users of Dipeptidyl Peptidase 4 Inhibitors (DPP-4i), by Nonalcoholic Fatty Liver Disease (NAFLD) Status
CV indicates cardiovascular; HF, heart failure; and MACE, major adverse cardiovascular events.
Figure 2.
Figure 2.. Cumulative Incidence of Major Adverse Cardiovascular Events (MACE) and Hospitalization for Heart Failure (HHF) Among Patients With Diabetes, by Nonalcoholic Fatty Liver Disease (NAFLD) Status
DPP-4 indicates dipeptidyl peptidase 4; GLP-1RA, glucagon-like peptide-1 receptor agonists; HR, hazard ratio; and SGLT-2, sodium glucose cotransporter-2.
Figure 3.
Figure 3.. Outcomes for the 1:1 Propensity Score–Matched Cohort of New Users of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) vs New Users of Dipeptidyl Peptidase 4 Inhibitors (DPP-4i), by Nonalcoholic Fatty Liver Disease (NAFLD) Status
CV indicates cardiovascular; HF, heart failure; MACE, major adverse cardiovascular events; and NA, not applicable.
See this image and copyright information in PMC

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