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

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.