Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes

Abstract

<b>Objective: </b>To assess associations between current use of SGLT2i, GLP-1RA and their combination and risk for MACCE and heart failure (HF) in people with type 2 diabetes. <p><b>Research Design and Methods:<strong> In three nested case-control studies involving people with </strong></b>type 2 diabetes<strong> in England and Wales (primary care data from CPRD and SAIL Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 controls.</strong><b> </b>Adjusted odds ratios for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens vs other combinations were estimated using conditional logistic regression and<strong> pooled using random-effects meta-analysis.</strong></p> <p><b>Results:<strong> Among 336,334 people with </strong></b>type 2 diabetes<strong> and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. 17,451 (4.2%) experienced a HF event in a cohort of 411,206 with </strong>type 2 diabetes<strong> and without HF. Compared with other combination regimens, the adjusted pooled odds ratio and 95% confidence interval (CI) for MACCE associated with SGLT2i regimens was </strong>0<strong>.</strong>82 (95% CI 0<strong>.</strong>73-0<strong>.</strong>92); with <strong>GLP-1RA regimens 0.93 (95% CI 0.81-1.06), and with the SGLT2i/GLP-1RA combination </strong>0<strong>.</strong>70 (95% CI 0<strong>.</strong>50-0<strong>.</strong>98)<strong>.</strong> Corresponding data for HF were: SGLT2i, 0<strong>.</strong>49 (95% CI 0<strong>.</strong>42-0<strong>.</strong>58); GLP-1RA, 0<strong>.</strong>82 (95% CI 0<strong>.</strong>71-0<strong>.</strong>95); <strong>and SGLT2i/GLP-1RA combination, </strong>0<strong>.</strong>43 (95% CI 0<strong>.</strong>28-0<strong>.</strong>64).</p> <p><b>Conclusions:</b> SGLT2i and <strong>SGLT2i/GLP-1RA</strong> combination regimens may be beneficial in primary prevention of MACCE and heart failure and GLP-1RA for heart failure. These data call for primary prevention trials using these agents and their combination.</p>

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