Combination Treatment of SGLT2 Inhibitors and GLP-1 Receptor Agonists: Symbiotic Effects on Metabolism and Cardiorenal Risk

Introduction: When treating type 2 diabetes, drugs that cause hypoglycemia and weight gain should, if possible, be avoided. In addition, due to the increased incidence and prevalence of cardiovascular disease, cardiac events and heart failure, as well as the accelerated renal decompensation that may occur with type 2 diabetes, hypoglycemic agents that have the potential to lower cardiac and renal risk should be utilized as early as possible in the course of the disease. Methods: This is a literature review of the efficacy of combined treatment with a glucagon-like peptide 1 (GLP-1) agonist and a sodium glucose cotransporter-2 (SGLT2) inhibitor in lowering glycated hemoglobin (HbA1c) level, cardiac risk, cardiac events and renal decompensation. Results: Evidence is presented which shows that the efficacy of combined SGLT2 inhibitor/GLP-1 receptor agonist therapy is additive in lowering HbA1c level, systolic blood pressure and body weight. This combined therapy also has the potential to cause further reductions in major cardiovascular events and renal decompensation than those achieved with either drug used as monotherapy or in combination with other hypoglycemic agents. Conclusion: The combination of a GLP-1 agonist and an SGLT2-inhibitor has additive effects on lowering HbA1c and systolic blood pressure, body weight and cardiac risk and has the potential to synergistically reduce cardiovascular events and decelerate renal decompensation. A large prospective study of this combination is needed to prove that this synergism, especially as it applies to cardiac risk factors, cardiac events and mortality and preservation of renal function, is proven.