Target trial emulation of cardiovascular outcome trials of medications used to treat type 2 diabetes using real-world data: a systematic review of observational studies.

BACKGROUND AND OBJECTIVES

Cardiovascular outcome trials are mandated by the US Food and Drug Administration to assess the cardiovascular safety of new antidiabetic medications before entering the market. However, these trials often involve highly selective populations and results may not generalize to routine practice.

METHODS

Our study aimed to synthesize observational studies to assess the generalizability of cardiovascular outcome trials to routine practice. We systematically reviewed observational studies that were target trial emulations of previous cardiovascular outcome trials for dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter-2 (SGLT-2) inhibitors among patients with type 2 diabetes. We searched the MEDLINE, EMBASE, and Cochrane databases for observational studies that focused on trial emulation or cross-sectional studies that reported the proportion of real-world patients eligible for completed trials.

RESULTS

Nineteen studies were included in our systematic review, including four cohort studies that were target trial emulations of previous randomized controlled trials (RCTs) and 15 cross-sectional studies that evaluated trial eligibility. Results between RCTs and real-world data (RWD) were concordant for all drug classes in finding noninferiority. The median eligibility percentage ranged from 13% to 31% for SGLT-2 inhibitor trials and 12% to 43% for GLP-1 receptor agonist trials.

CONCLUSION

These results suggest that, while RCTs and RWD are concordant in their estimates, the trials lack representativeness. More research is needed on the emulation of cardiovascular outcome trials using RWD to understand how different emulation methods may impact findings.