Cardiovascular Outcomes of Insulin Degludec Versus Insulin Glargine in Trial-Eligible and Ineligible Populations: A DEVOTE-Inspired Target Trial Emulation Using the Swedish National Diabetes Register.

Abstract

Aims: To compare cardiovascular outcomes associated with the initiation of insulin degludec versus insulin glargine using a target trial emulation approach in nationwide real-world data.

Materials and methods: We conducted a nationwide observational cohort study using Swedish health registers, including the National Diabetes Register. Individuals with type 2 diabetes initiating insulin degludec or insulin glargine between 2012 and 2022 were included. Two complementary approaches were applied: a trial-eligible emulation cohort reflecting the eligibility criteria of the DEVOTE trial, and a trial-ineligible emulation cohort representing routine clinical practice. The primary outcome was major adverse cardiovascular events (MACE, i.e., myocardial infarction, stroke and cardiovascular mortality). Secondary outcomes included the individual components of MACE, all-cause mortality and heart failure. Average treatment effects were estimated using longitudinal targeted minimum loss-based estimation.

Results: Among 96 731 individuals identified, 44 890 met the study eligibility criteria and were included in the analyses. In the trial-eligible cohort, degludec was associated with a similar risk of MACE compared with glargine (risk ratio: 1.10; 95% CI: 0.91-1.34; p = 0.34), but a significantly lower risk of all-cause mortality (risk ratio: 0.75; 95% CI: 0.62-0.92; p = 0.002). In the trial-ineligible emulation cohort, degludec was associated with lower risks of MACE (risk ratio: 0.80; 95% CI: 0.67-0.95; p = 0.004) as well as reduced risks of all-cause mortality, cardiovascular mortality, non-fatal stroke and heart failure.

Conclusions: In this nationwide study, degludec was associated with a lower risk of all-cause mortality compared with glargine, consistently observed in both trial-eligible and trial-ineligible populations, despite similar cardiovascular risk in the trial-eligible cohort.