The sodium–glucose cotransporter 2 inhibitor empagliflozin was associated with lower all-cause mortality compared with dipeptidyl peptidase-4 inhibitors among patients with type 2 diabetes in an observational analysis designed to emulate a randomized clinical trial, according to research published in BMJ Open Diabetes Research & Care.
Investigators used UK primary care electronic health records to conduct a trial-emulation study of 62,503 adults with type 2 diabetes who initiated either empagliflozin or a dipeptidyl peptidase-4 (DPP-4) inhibitor between January 1, 2014, and December 31, 2022. The analysis evaluated whether the mortality benefit reported in the EMPA-REG randomized trial might also be observed in a broader, real-world population that included patients who would not have met the trial’s eligibility criteria.
Among the 13,239 patients who initiated empagliflozin, 11,011 (83%) would not have qualified for the original EMPA-REG trial. Overall, only 20.8% of the full cohort met the randomized trial’s eligibility criteria.
In total, 13,239 patients initiated empagliflozin and 49,264 initiated a DPP-4 inhibitor, which served as the active comparator. During follow-up of up to 9.6 years—representing 200,646 person-years—death occurred in 551 patients receiving empagliflozin (4.2%) and in 6,589 patients receiving DPP-4 inhibitors (13.4%).
After adjustment for demographic and clinical variables, initiation of empagliflozin was associated with a lower risk of all-cause mortality compared with DPP-4 inhibitors, with an adjusted hazard ratio of 0.76.
The investigators estimated a 3-year absolute mortality risk reduction of approximately 2 percentage points for patients treated with empagliflozin, corresponding to a number needed to treat of 47 to prevent one death over 3 years.
Unlike the EMPA-REG trial, which enrolled patients with type 2 diabetes and established cardiovascular disease, the observational analysis included adults aged 18 years or older with type 2 diabetes who newly initiated empagliflozin or a DPP-4 inhibitor in routine clinical practice.
Despite the broader inclusion criteria, mortality results were similar among patients who would have met EMPA-REG eligibility criteria and those who would not have qualified.
“Our findings confirm that the mortality benefits of empagliflozin observed in the EMPA-REG randomized clinical trial are realized in real-world practice,” wrote lead author David K. Ryan of the Institute of Health Informatics at University College London and colleagues.
Because the study was observational rather than randomized, the findings demonstrate an adjusted association between empagliflozin use and lower mortality rather than establishing causation.
Disclosures can be found in the study.
