Empagliflozin reduces mortality in real-world type 2 diabetes patients, including those excluded from pivotal trials

• Empagliflozin was associated with significantly lower all-cause mortality compared with DPP-4 inhibitors across the full study population (adjusted HR 0.76, 95% CI 0.69 to 0.83).
• The mortality benefit was consistent regardless of whether patients met EMPA-REG RCT eligibility criteria (p-interaction=0.27), supporting broader real-world use.
• Sensitivity analyses using IPTW and E-values confirmed the robustness of findings against potential unmeasured confounding.

These findings apply to adults with type 2 diabetes who are candidates for SGLT2 inhibitor therapy, including those without established cardiovascular disease. The results are most relevant to patients managed in primary care settings similar to the UK healthcare system, given the use of THIN database data from 2014 to 2022.

This was not a randomized trial - it used statistical methods to try to replicate what an RCT would find. The active comparator design (DPP-4 inhibitors vs placebo) helps reduce bias, but unmeasured factors like frailty could still affect results. The study did not examine safety outcomes or other SGLT2 inhibitors besides empagliflozin.

• Observational design means residual confounding is possible despite rigorous methods.
• Cause-specific mortality data were not available, so only all-cause mortality could be assessed.
• The study used UK primary care data, so results may not apply to all healthcare settings.
• Safety outcomes were not assessed in this analysis.