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- Title
Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status.
- Authors
Bea, Sungho; Jeong, Han Eol; Filion, Kristian B.; Yu, Oriana HY; Cho, Young Min; Lee, Bon Hyang; Chang, Yoosoo; Byrne, Christopher D.; Shin, Ju-Young
- Abstract
Key Points: Question: Are sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) associated with reduced cardiovascular risk in patients with type 2 diabetes and concomitant nonalcoholic fatty liver disease (NAFLD)? Findings: In this population-based cohort study, GLP-1RA and SGLT-2i therapy were associated with reduced risk of major adverse cardiovascular events in patients with T2D and across baseline NAFLD status. Moreover, SGLT-2i therapy was associated with reduced risk of hospitalization for heart failure. Meaning: These results support the current guidelines that recommend GLP-1RA as the first-line of therapy for patients with T2D and NAFLD and highlight the potential of SGLT-2i as a promising option for cardiovascular disease prevention regardless of NAFLD status. This cohort study investigates the outcomes of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among patients with type 2 diabetes in South Korea, by the presence or absence of nonalcoholic fatty liver disease (NAFLD). 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.
- Subjects
SOUTH Korea; GLUCAGON-like peptide 1; MAJOR adverse cardiovascular events; NON-alcoholic fatty liver disease; HYPOGLYCEMIC agents; RETROSPECTIVE studies; ACQUISITION of data; TYPE 2 diabetes; TREATMENT effectiveness; COMPARATIVE studies; MEDICAL records; DESCRIPTIVE statistics; RESEARCH funding; SODIUM-glucose cotransporter 2 inhibitors; DATA analysis software; LONGITUDINAL method; HEART failure; ENZYME inhibitors; POISSON distribution; EVALUATION; DISEASE complications
- Publication
JAMA Network Open, 2023, Vol 6, Issue 12, pe2349856
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2023.49856