Cardiovascular and renal outcomes of dual combination therapies with glucagon-like peptide-1 receptor agonists and sodium-glucose transport protein 2 inhibitors: a systematic review and meta-analysis
A synthesis of trial sub-analyses and large real-world cohorts found that combining a GLP-1 receptor agonist with an SGLT2 inhibitor (and in some cases finerenone) protects the heart and kidneys more than either drug alone in type 2 diabetes.
Background
SGLT2 inhibitors, GLP-1 receptor agonists, and the nonsteroidal MRA finerenone each reduce cardiovascular and kidney events through complementary mechanisms, raising the question of whether their combination yields additive benefit.
Study design
The review searched MEDLINE and Embase and included four post-hoc analyses of randomized trials and ten observational studies, using meta-regression for RCT interaction effects and random-effects meta-analysis for observational comparisons of combination versus monotherapy.
Key findings
Across RCTs, GLP-1 receptor agonist benefit on major adverse cardiac events, cardiovascular and all-cause mortality, heart failure hospitalization, and renal composite outcomes was consistent regardless of baseline SGLT2 inhibitor use. In observational data, GLP-1 RA plus SGLT2i combination reduced MACE (e.g., HR 0.59 vs SGLT2i monotherapy) and serious renal events (HR 0.43), and SGLT2i plus finerenone reduced all-cause mortality and major adverse kidney events versus either monotherapy.
Clinical implications
The findings support broader clinical use of dual-agent cardiorenal regimens in type 2 diabetes, while underscoring the need for prospective trials powered for hard outcomes to confirm the magnitude of additive benefit.
Category
Research
Source
Cardiovascular Diabetology
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