Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials.

Abstract

BACKGROUND\nIn international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes.\n\n\nMETHODS\nWe assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions.\n\n\nRESULTS\nThe estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n=12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n=12,515, HR 0.95, 95% CI 0.83- 1.09) and in Europe (SGLT2Is n=19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n=22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n=15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n=17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28. Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (p=0.0094). The effect of SGLT2Is was significantly smaller in Europe (n=18,653, HR 0∙86, 95% CI 0∙78-0∙95) than in the ROW (n= 12,463, HR 0∙68, 95% CI 0∙61-0∙76, p=0.0024). The smaller effect in North America (n= 9776, HR 0∙76, 95% CI 0∙66-0.87) did not differ significantly from that in the ROW (p=0.2370).\n\n\nCONCLUSIONS\nThe effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1Ras by geographical regions.