Combination therapy with GLP‐1 receptor agonist and SGLT2 inhibitor

• Published in: Diabetes, obesity & metabolism Vol. 19; no. 10; pp. 1353 - 1362
• Main Author: DeFronzo, Ralph A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2017; Wiley Subscription Services, Inc
• Subjects: cardiovascular disease; Combination therapy; Creatinine; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - pathology; Diabetic Nephropathies - prevention & control; Disease Progression; Drug Therapy, Combination - methods; End-stage renal disease; GLP-1 receptor agonists; GLP‐1 receptor agonist; Glucagon; Glucagon-Like Peptide-1 Receptor - agonists; glycaemic control; Health risk assessment; Humans; Hypoglycemic Agents - administration & dosage; Inflammation; Kidney diseases; Kidney Failure, Chronic - etiology; Kidney Failure, Chronic - prevention & control; Kidney transplantation; SGLT2i inhibitor; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; type 2 diabetes mellitus; type 2 diabetes mellitus; cardiovascular disease; SGLT2i inhibitor; glycaemic control; GLP-1 receptor agonist
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.12982

The SGLT2 inhibitors (SGLTi) and glucagon‐like‐1 receptor agonists (GLP‐1 RAs) effectively reduce HbA1c, but via very different mechanisms, making them an effective duet for combination therapy. Recently, drugs in both of these antidiabetic classes have been shown to reduce cardiovascular events, most probably by different mechanisms. SGLT2i appear to exert their CV protective actions by haemodynamic effects, while GLP‐1 RAs work via anti‐atherogenic/anti‐inflammatory mechanisms, raising the possibility that combined therapy with these 2 classes may produce additive CV benefits. The SGLT2i and GLP‐1 RAs also reduced macroalbuminuria, decreased the time for doubling of serum creatinine, and slowed the time to end‐stage renal disease. In this perspective, we review the potential benefit of combination SGLT2i/GLP‐1 RA therapy on metabolic‐cardiovascular‐renal disease in patients with type 2 diabetes mellitus.