Cardiovascular and renal effects of the combination therapy of a GLP-1 receptor agonist and an SGLT2 inhibitor in observational real-life studies

BACKGROUND: Combining a glucagon-like peptide-1 receptor agonist (GLP-1RA) and an sodium-glucose cotransporter 2 inhibitor (SGLT2i) improved cardiovascular (and renal) prognosis compared to either monotherapy in several post-hoc exploratory analyses of randomized controlled trials (RCTs) versus placebo carried out in patients with type 2 diabetes (T2DM) and high cardiovascular/renal risk. The aim of the present work is to verify if such a benefit of the combined therapy is also present in real-life clinical practice. METHODS: An extended search of the literature was performed to select observational retrospective studies that compared cardiovascular and/or renal outcomes in patients with T2DM treated with a GLP-1RA/SGLT2i combination versus patients treated with either GLP-1RA monotherapy or SGLT2i monotherapy, in addition to standard of care therapy. RESULTS: Nine observational studies showed that a GLP-1RA/SGLT2i combination is associated with a greater reduction in major adverse cardiovascular events (MACEs), hospitalization for heart failure and all-cause-mortality when compared to either GLP-1RA alone or SGLT2i alone, without obvious differences between the two monotherapies, including regarding heart failure. Results were obtained in different populations, including patients with atherosclerotic cardiovascular disease and/or heart failure. Only three observational studies gave information on renal outcomes, with a greater benefit when the GLP-1RA/SGLT2i combination was compared with GLP-1RA alone or SGLT2i alone. CONCLUSION: In real-life conditions, the GLP-1RA/SGLT2i combination reduced cardiovascular and renal outcomes compared with both GLP-1RA monotherapy and SGLT2i monotherapy. Overall, observational studies confirm the results reported in post-hoc exploratory analyses of RCTs versus placebo.