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

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.