Meta-analyses of Results From Randomized Outcome Trials Comparing Cardiovascular Effects of SGLT2is and GLP-1RAs in Asian Versus White Patients With and Without Type 2 Diabetes

Abstract

BACKGROUND Results of cardiovascular outcome trials (CVOTs) suggest Asians may derive greater benefit than Whites from newer classes of antihyperglycemic medications. PURPOSE To provide summary hazard ratio (HR) estimates for cardiovascular efficacy of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) stratified by race (Asian vs. White). DATA SOURCES A systematic review performed in PubMed from 1 January 2015 to 8 December 2020. STUDY SELECTION Randomized placebo-controlled CVOTs of SGLT2is and GLP-1RAs that reported HRs (95% CIs) for 1) major adverse cardiovascular event (MACE) in patients with diabetes and 2) cardiovascular (CV) death/hospitalization for heart failure (HHF) in patients with HF and reduced ejection fraction (HFrEF). DATA EXTRACTION AND SYNTHESIS HRs (95% CIs) for selected outcomes in Asians and Whites were extracted from each trial, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects meta-analyses were performed to examine differences between the selected outcomes in Asians versus Whites. RESULTS In four SGLT2i trials in type 2 diabetes, the MACE outcome HR (95% CI) in 3,298 Asians versus 20,258 Whites was 0.81 (0.57, 1.04) vs. 0.90 (0.80, 1.00), respectively (Pinteraction = 0.46). In two SGLT2i trials in patients with HFrEF, the CV death/HHF outcome HR in 1,788 Asians versus 5,962 Whites was 0.60 (0.47, 0.74) vs. 0.82 (0.73, 0.92), respectively (Pinteraction = 0.01). In six GLP-1RA trials, the MACE outcome HR in 4,195 Asians versus 37,530 Whites was 0.68 (0.53, 0.84) vs. 0.87 (0.81, 0.94), respectively (Pinteraction = 0.03). LIMITATIONS Lack of individual patient–level data, relatively short duration of trial observation, and lack of granular categorization of race within broadly defined Asian subgroups. CONCLUSIONS Compared with Whites, Asians may derive greater CV death/HHF benefit from SGLT2is in patients with HFrEF, and MACE benefit from GLP-1RAs in patients with type 2 diabetes.