Diabetes, obesity & metabolismNov 28, 2024

Early combined treatment with SGLT2 inhibitors and GLP-1 or dual GIP/GLP-1 receptor agonists in type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) may improve glycaemic control in individuals with type 2 diabetes (T2D).

The combination of SGLT2i and GLP-1 RA targets complementary disease mechanisms and may enhance the effectiveness of treatment.
Both SGLT2i and GLP-1 RA are associated with reduced risks of cardiorenal complications in T2D.
SGLT2i may be particularly effective in preventing kidney dysfunction and heart failure.
GLP-1 RA may have a stronger impact on reducing the risk of atherosclerotic cardiovascular disease.
Combination therapy may lead to weight loss, which could have effects that help reverse the progression of T2D.

Simplified

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.

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Early combined treatment with SGLT2 inhibitors and GLP-1 or dual GIP/GLP-1 receptor agonists in type 2 diabetes

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