Diabetes, Obesity and Metabolism: Published on November, 2024

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This review synthesizes the available evidence on the use of SGLT2i (Empagliflozin, Dapagliflozin, Canagliflozin, Ertugliflozin) and GLP-1 (Semaglutide, Liraglutide, Dulaglutide, Exenatide) based therapies for T2D and provides a rationale for their combination.

The review examines the impact of GLP-1 RAs and SGLT2is on glycemic control and cardiovascular–renal risk factors and data regarding the cardiovascular protective benefits associated with these treatments.

Furthermore, it highlights the renal protective advantages of SGLT2is and GLP-1 RAs, including dual GIP/GLP-1 RAs, and evaluates the safety profile of combination therapy. Insights from current guidelines regarding the use of combination therapy are also included.

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 cardio renal 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 favorable safety profiles.

Finally, weight loss with combination therapy may have disease-modifying effects that may reverse T2D progression.

Early combination therapy with SGLT2i + GLP-1 RA or Dual GIP/GLP-1 RA offers superior glycemic control, weight loss, and cardiovascular/renal protection in type 2 diabetes.

Authors recommend that this combination of SGLT2i with GLP-1 RA or dual GIP/GLP-1 RA should be considered in people with T2D regardless of treatment with Metformin.

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