Empagliflozin reduces mortality in real-world type 2 diabetes patients, including those excluded from pivotal trials
Last updated May 4, 2026
Key finding
A trial emulation using UK primary care data from 62,503 people with type 2 diabetes found that empagliflozin reduced the risk of death by 24% compared with DPP-4 inhibitors, with consistent benefits in patients who would have been excluded from the original EMPA-REG trial.
Researchers used UK electronic health records to estimate how well empagliflozin works in real-world patients with type 2 diabetes, including the 83% who would not have qualified for the original EMPA-REG trial. Over up to 9.6 years of follow-up, empagliflozin reduced the risk of death by 24% compared with an older drug class, with consistent benefits across all patient groups.
Quick read
Study at a glance
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EvidenceScore™
Moderate
Study type
Cohort
Follow-up
Long-Term (> 12 mo)
Risk of bias
Some Concerns
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Plain-language summary
What this paper says
A plain-language read of the study’s main message and where it applies.
Study focus
A trial emulation using UK primary care data from 62,503 people with type 2 diabetes found that empagliflozin reduced the risk of death by 24% compared with DPP-4 inhibitors, with consistent benefits in patients who would have been excluded from the original EMPA-REG trial.
Published in
Journal Reference
Publication details and source links for this paper.
Ryan DK, Keogh RH, Williamson E, et al. Enhancing evidence-based care using trial emulation in electronic health records: real-world effects of empagliflozin in people with type 2 diabetes. BMJ Open Diabetes Res Care. 2026;14(1):e005672. doi:10.1136/bmjdrc-2025-005672
Main Effects
All-cause mortality ↓ by 24% with empagliflozin vs DPP-4 inhibitors (aHR 0.76)
Consistent benefit in RCT-ineligible patients (83% of real-world users)
NNT of 47 to prevent one death over 3 years
Evidence Suggest
- 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.
Who this applies to
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.
Keep in Mind
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.
Between the Lines
- 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.
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