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Cardiometabolic Benefits and Risks of Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitor and Glucagon-Like Peptide-1

Dalia Tantawy1, Maram Rabih Musa Rabih2, Razan Seifeldin Ibrahim Mohamed3

  • 1General Medicine, George Eliot Hospital, West Midlands, GBR.

Cureus
|November 10, 2025
PubMed

Insights

Combining sodium-glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offers significant cardiometabolic protection for type 2 diabetes patients. This combination therapy enhances cardiovascular health, improves glycemic control, and promotes weight loss without substantial safety concerns.

Area of Science:

  • Endocrinology
  • Cardiology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) management increasingly prioritizes cardiometabolic protection.
  • Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) possess complementary mechanisms for managing T2DM.
  • Combination therapy with SGLT2is and GLP-1 RAs presents a promising strategy for enhanced patient outcomes.

Purpose of the Study:

  • To systematically review the cardiometabolic benefits and risks associated with SGLT2i and GLP-1 RA combination therapy in T2DM patients.
  • To evaluate the impact of this combination on cardiovascular, renal, glycaemic, and safety outcomes.
  • To assess the synergistic effects of combining these two drug classes.

Main Methods:

  • A systematic literature search was performed across PubMed, Scopus, Embase, and Web of Science.
  • Included randomized controlled trials (RCTs) published between 2020 and 2025, adhering to PRISMA guidelines.
  • Data extraction focused on cardiovascular, renal, glycaemic, and safety outcomes, with quality assessed using the Cochrane RoB 2 tool.

Main Results:

  • Combination therapy demonstrated additive cardioprotective effects and superior glycaemic control (HbA1c reduction).
  • GLP-1 RAs reduced MACE and heart failure hospitalizations irrespective of SGLT2i use; SGLT2i benefits were maintained with GLP-1 RAs.
  • The combination led to significant reductions in weight and systolic blood pressure compared to monotherapy, with a manageable safety profile.

Conclusions:

  • The combination of SGLT2is and GLP-1 RAs offers synergistic benefits for cardiovascular risk reduction, glycaemic control, weight management, and blood pressure in T2DM.
  • The safety profile is consistent with individual drug classes, with no new significant adverse events identified.
  • This combination therapy is a potent strategy for high-risk T2DM patients, although further prospective trials specifically designed for combination therapy are warranted.
Keywords:
cardiovascular outcomescombination therapyglp-1 receptor agonistsglt2 inhibitorsystematic reviewtype 2 diabetes

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