Key result
SGLT2 inhibitors linked to ~22% lower risk of death, MI, or stroke vs. DPP-4 inhibitors.
Why the study?
Head-to-head comparisons of SGLT2 inhibitors versus DPP-4 inhibitors remain limited in East Asian populations with type 2 diabetes.
Does SGLT2 inhibitor therapy reduce the composite risk of all-cause death, myocardial infarction, or stroke compared to DPP-4 inhibitors in East Asian adults with type 2 diabetes on combination therapy?
Cohort (n=89,554)
Does SGLT2 inhibitor therapy reduce the composite risk of all-cause death, myocardial infarction, or stroke compared to DPP-4 inhibitors in East Asian adults with type 2 diabetes on combination therapy?
Hazard Ratio: 0.78 (95% CI 0.72–0.84)
Absolute Event Rate: 3.42% vs 4.38%
p-value: p=<0.001
In a nationwide observational cohort of Korean adults with type 2 diabetes, initiating SGLT2 inhibitors as part of combination therapy was associated with a significant reduction in the composite of death, MI, or stroke compared to DPP-4 inhibitors, driven primarily by lower all-cause mortality.
May inform preferential SGLT2 inhibitor use over DPP-4 inhibitors in type 2 diabetes; leaves open confirmation by randomized trials.
Head-to-head comparisons of sodium–glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors remain limited in East Asian populations. We compared outcomes in Korean adults with type 2 diabetes entering combination oral therapy. Using the Korean National Health Insurance Service database (2013–2023), adults aged ≥ 39 years with newly treated type 2 diabetes between 2015 and 2019 who reached combination therapy of ≥ 2 antidiabetic classes including an SGLT2 or DPP-4 inhibitor, with ≥ 90 consecutive days of prescription coverage, were identified; the primary analysis used a day-90 landmark, with 1:1 matching among patients event-free at that landmark; marginal Cox models with pair-clustered variance were fitted. Among 44,777 matched pairs, SGLT2 inhibitors were associated with a lower risk of the composite of all-cause death, myocardial infarction, or stroke (5-year cumulative incidence 3.42% vs. 4.38%; HR 0.78, 95% CI 0.72–0.84; p < 0.001), driven by all-cause death (2.08% vs. 2.95%; HR 0.69, 0.62–0.76; p < 0.001). Neither stroke (HR 0.90, 0.79–1.04) nor myocardial infarction (HR 1.02, 0.82–1.27) differed. Safety events per 1,000 person-years (DPP-4 inhibitor vs. SGLT2 inhibitor) were: genital infection 34.0 vs. 55.4; acute kidney injury 6.4 vs. 5.0; hypovolaemia 10.8 vs. 10.8; diabetic ketoacidosis 0.71 vs. 0.73. In this nationwide cohort, SGLT2 inhibitors were associated with a lower risk of the composite of all-cause death, myocardial infarction, or stroke, driven mainly by lower all-cause mortality; neither cardiovascular component differed significantly. The associations were consistent in sensitivity analyses and showed moderate robustness in the E-value assessment, and should be interpreted within the limits of observational data.
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Cha et al. (2026) conducted a cohort in Type 2 diabetes (n=89,554). SGLT2 inhibitors vs. DPP-4 inhibitors was evaluated on Composite of all-cause death, myocardial infarction, or stroke (HR 0.78, 95% CI 0.72-0.84, p=<0.001). SGLT2 inhibitors were associated with a 22% lower risk of the composite of all-cause death, myocardial infarction, or stroke compared to DPP-4 inhibitors (HR 0.78).
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