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Combination cardiometabolic therapy in type 2 diabetes: optimizing SGLT2 inhibitor and GLP‑1 receptor agonist use

Laura R Porterfield1, Saad Nadeem2, Dallin Swanson3

  • 1Department of Family Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, USA.

Current Atherosclerosis Reports
|July 18, 2026
PubMed
Abstract

Insights

Combined sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer complementary benefits for type 2 diabetes patients. A phenotype-guided approach optimizes their use for managing cardiometabolic risk.

Area of Science:

  • Cardiology
  • Endocrinology
  • Nephrology

Background:

  • Type 2 diabetes (T2D) management requires addressing significant cardiometabolic risk.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are key pharmacotherapies.
  • Understanding their combined effects is crucial for optimizing patient outcomes.

Purpose of the Study:

  • To review evidence on combined SGLT2i and GLP-1RA therapy in T2D.
  • To focus on cardiometabolic outcomes and practical treatment strategies.
  • To evaluate the synergistic potential of these drug classes.

Main Methods:

  • Review of cardiovascular outcomes trials (CVOTs).
  • Analysis of real-world evidence.
  • Examination of randomized data on drug class interactions.

Main Results:

  • SGLT2is and GLP-1RAs provide complementary, non-redundant benefits for cardiovascular, kidney, and metabolic health.
  • SGLT2is excel in reducing heart failure hospitalizations and slowing kidney disease progression.
  • GLP-1RAs are more effective in reducing atherosclerotic events, particularly stroke, with expanding roles in CKD and HFpEF.

Conclusions:

  • Combined SGLT2i and GLP-1RA therapy addresses multiple risk domains via complementary mechanisms.
  • A phenotype-guided approach, aligning therapy with dominant comorbidities (ASCVD, HF, CKD, obesity), is emerging as optimal.
  • Combination therapy is most effective for individuals with overlapping high-risk phenotypes, despite remaining residual risk.
Keywords:
Cardiovascular diseaseCombination therapyDiabetesGLP-1 receptor agonistsKidney diseaseSGLT2 inhibitors

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