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

Catarina Vale; Inês Mariana Lourenço; Gabriela Jordan; Ilya Golovaty; Hugo Torres; Tannaz Moin; Martin Buysschaert; João Sérgio Neves; Michael Bergman

doi:10.1111/dom.16077

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

Diabetes Obes Metab. 2024 Nov 27. doi: 10.1111/dom.16077. Online ahead of print.

Authors

Catarina Vale^{1

2}, Inês Mariana Lourenço¹, Gabriela Jordan³, Ilya Golovaty^{4

5}, Hugo Torres⁶, Tannaz Moin^{6

7}, Martin Buysschaert⁸, João Sérgio Neves^{1

9}, Michael Bergman¹⁰

Affiliations

¹ Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
² Department of Internal Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal.
³ Scripps Health in San Diego, San Diego, California, USA.
⁴ General Medicine Service, VA Puget Sound Health Care System, Seattle, Washington, USA.
⁵ Division of General Internal Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
⁶ David Geffen School of Medicine, University of California, Los Angeles, California, USA.
⁷ HSR&D Center for the Study of Healthcare Innovation, Implementation & Policy, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
⁸ Department of Endocrinology and Diabetology, Université Catholique de Louvain, University Clinic Saint-Luc, Brussels, Belgium.
⁹ Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal.
¹⁰ Holman Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Population Health, VA New York Harbor Healthcare System, New York University Grossman School of Medicine, New York, New York, USA.

PMID: 39604324
DOI: 10.1111/dom.16077

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-Like peptide-1 receptor agonists (GLP-1 RA) are recommended in people with type 2 diabetes (T2D) for glycaemic control and for people with high cardiovascular risk. However, current guidelines do not specifically address the role of initial early combination therapy with SGLT2i and GLP-1 RA or dual gastric inhibitory polypeptide (GIP)/GLP-1 RA, but rather sequential initiation with either in T2D. This review synthesizes the available evidence on the use of SGLT2i and GLP-1-based therapies for T2D and provides a rationale for their combination. The combination of SGLT2i with GLP-1-based therapies addresses complementary pathophysiological mechanisms and enhances efficacy in achieving target haemoglobin A1C (HbA1c) levels. SGLT2i and GLP-1 RA also have been shown to prevent complications of T2D. While both classes reduce adverse cardiorenal events, SGLT2i has a predominant effect on prevention of kidney dysfunction and heart failure, whereas GLP-1 RA has a more marked effect on the risk of atherosclerotic cardiovascular disease. Both drug classes have favourable safety profiles. Finally, weight loss with combination therapy may have disease-modifying effects that may reverse T2D progression. We propose that the combination of SGLT2i with GLP-1 RA or dual GIP/GLP-1 RA should be considered for most patients with T2D who do not have contraindications.

Keywords: GLP‐1 receptor agonists; SGLT2 inhibitors; combination therapy; dual GIP/GLP‐1 receptor agonists; type 2 diabetes.

Publication types

Review

Abstract

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