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

Nov 28, 2024Diabetes & metabolism

Heart and kidney effects of combining GLP-1 receptor drugs with SGLT2 inhibitors in real-world studies

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Abstract

Nine observational studies indicate that a GLP-1RA/SGLT2i combination is associated with a greater reduction in major adverse cardiovascular events compared to either GLP-1RA or SGLT2i monotherapy.

The combination therapy is linked to reduced hospitalization for heart failure and lower all-cause mortality.
No significant differences were observed between the two monotherapies in terms of heart failure outcomes.
The findings are consistent across various patient populations, including those with atherosclerotic cardiovascular disease and/or heart failure.
Three studies provided data on renal outcomes, showing greater benefits of the combination therapy over monotherapies.

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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.

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

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