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Cardiovascular and renal protection of SGLT2i in early-stage type 2 diabetes: the DIAB-CV-AP study

Jorge Pablo-Ortega1, Manuel Portela-Romero2, Pilar Mazón-Ramos3

  • 1Centro de Salud de Potosi, Madrid Health Service, Potosi street, 7, Madrid, 28016, Spain.

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD
|August 21, 2026
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduced cardiovascular and renal events in type 2 diabetes mellitus (T2DM) patients. This study confirms SGLT2i benefits in primary care settings, showing reduced mortality and robust findings.

Area of Science:

  • Cardiovascular Medicine
  • Nephrology
  • Endocrinology
  • Real-world evidence

Background:

  • Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular (CV) and renal benefits in clinical trials.
  • Type 2 diabetes mellitus (T2DM) patients often require treatment intensification beyond metformin monotherapy.
  • Evaluating SGLT2i's real-world impact on CV and renal outcomes in this population is crucial.

Purpose of the Study:

  • To analyze the preventive effect of SGLT2i on cardiovascular and renal events.
  • To assess SGLT2i's impact on all-cause mortality in primary care T2DM patients.
  • To evaluate the robustness of these findings against unmeasured confounding factors.

Main Methods:

  • Retrospective cohort study utilizing the Spanish National Health System primary care database (BIFAP).
  • Patients with T2DM on metformin initiating a second non-insulin antidiabetic drug (NIAD) were classified as SGLT2i or other NIAD users.
  • Propensity score matching and Cox regression were employed to analyze CV events, renal events, and mortality, with E-values assessing confounding.

Main Results:

  • SGLT2i use was associated with a significantly lower risk of renal events (HR 0.303; p < 0.001) and cardiovascular events (HR 0.702; p < 0.001).
  • A substantial reduction in all-cause mortality was observed in the SGLT2i group (HR 0.285; p < 0.001).
  • Robust E-values indicated the findings were resilient to unmeasured confounding, and no increase in adverse events was noted.

Conclusions:

  • In primary care T2DM patients needing treatment intensification, SGLT2i significantly reduces cardiovascular events, renal progression, and all-cause mortality.
  • The observed benefits are substantial and supported by robust statistical measures against confounding.
  • SGLT2i represents a valuable therapeutic option for managing T2DM in real-world primary care settings.
Keywords:
Cardiovascular riskDiabetes mellitusKidney failureSGLT2i

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