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Early combination therapy with SGLT2i and GLP-1 RA or dual GIP/GLP-1 RA in type 2 diabetes

Catarina Vale1,2, Inês Mariana Lourenço1, Gabriela Jordan3

  • 1Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.

Diabetes, Obesity & Metabolism
|November 28, 2024
PubMed

Insights

Early combination therapy with sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) offers enhanced glycemic control and cardiorenal protection in type 2 diabetes (T2D). This approach addresses complementary mechanisms, potentially modifying disease progression.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Cardiology

Background:

  • Current type 2 diabetes (T2D) guidelines recommend sequential initiation of SGLT2 inhibitors (SGLT2i) or GLP-1 receptor agonists (GLP-1 RA).
  • Limited guidance exists on early combination therapy using SGLT2i, GLP-1 RA, or dual GIP/GLP-1 RA for T2D management.
  • Both SGLT2i and GLP-1 RA are established for glycemic control and reducing cardiovascular risk in T2D.

Purpose of the Study:

  • To review evidence supporting the combination of SGLT2i and GLP-1-based therapies in T2D.
  • To provide a rationale for utilizing early combination therapy in T2D management.
  • To explore the complementary pathophysiological mechanisms and enhanced efficacy of combined SGLT2i and GLP-1 RA therapy.

Main Methods:

  • Literature review synthesizing available evidence on SGLT2i and GLP-1-based therapies.
  • Analysis of mechanisms of action for individual drug classes and their combination.
  • Evaluation of evidence regarding cardiorenal protection and glycemic control.

Main Results:

  • Combination therapy enhances efficacy in achieving target HbA1c levels by addressing complementary pathophysiological mechanisms.
  • SGLT2i predominantly prevent kidney dysfunction and heart failure, while GLP-1 RA show a marked effect on atherosclerotic cardiovascular disease risk.
  • Both drug classes possess favorable safety profiles, and combination therapy promotes weight loss, potentially offering disease-modifying effects.

Conclusions:

  • Combination therapy with SGLT2i and GLP-1 RA or dual GIP/GLP-1 RA should be considered for most T2D patients without contraindications.
  • This combination offers superior glycemic control and cardiorenal benefits compared to monotherapy.
  • Early combination therapy may have disease-modifying potential, possibly reversing T2D progression.
Keywords:
GLP‐1 receptor agonistsSGLT2 inhibitorscombination therapydual GIP/GLP‐1 receptor agoniststype 2 diabetes

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