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

Objective: 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.

Research Design and Methods: In three nested case-control studies involving people with type 2 diabetes 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. 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 pooled using random-effects meta-analysis.

Results: Among 336,334 people with type 2 diabetes 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 type 2 diabetes 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 0.82 (95% CI 0.73-0.92); with GLP-1RA regimens 0.93 (95% CI 0.81-1.06), and with the SGLT2i/GLP-1RA combination 0.70 (95% CI 0.50-0.98). Corresponding data for HF were: SGLT2i, 0.49 (95% CI 0.42-0.58); GLP-1RA, 0.82 (95% CI 0.71-0.95); and SGLT2i/GLP-1RA combination, 0.43 (95% CI 0.28-0.64).

Conclusions: SGLT2i and SGLT2i/GLP-1RA 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.