Cardiorenal Protection in Type 2 Diabetes: A Systematic Review Comparing Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors
Abstract
Type 2 diabetes mellitus (T2DM) is associated with substantial cardiovascular and renal morbidity and premature mortality. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiorenal events beyond their glucose-lowering effects. This systematic review compared cardiovascular, heart failure, kidney, mortality, metabolic, and safety outcomes of the two classes of medications and evaluated evidence for complementary use. Randomized controlled trials, systematic reviews and meta-analyses, and large comparative observational studies of adults with type 2 diabetes reporting relevant cardiovascular, renal, mortality, metabolic, or safety outcomes were eligible. Glycemia-only studies without relevant clinical outcomes, pediatric and preclinical studies, case reports, editorials, and noninformative reports were excluded. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from January 2010 through August 30, 2026, supplemented by Google Scholar and backward and forward citation searching. Risk of bias was assessed using RoB 2 for randomized trials, ROBINS-I for nonrandomized comparative studies, and AMSTAR 2 for systematic reviews and meta-analyses. Certainty of evidence was assessed at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Because of heterogeneity across populations, interventions, outcomes, and study designs, results were evaluated using a…
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