Beyond glycemic control: cardiovascular and kidney benefits of GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide: a narrative review
- 1Department of Internal Medicine – Ward B, Health Care Complex in Ostrów Wielkopolski, Inpatient Treatment
- 2Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences
- 3Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences
Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome reflects the complex interplay among cardiovascular disease, chronic kidney disease, type 2 diabetes, and obesity. GLP-1 receptor agonists and tirzepatide have emerged as important therapeutic options within CKM syndrome, although the strength and maturity of evidence differ across individual agents and cardiovascular and kidney outcomes. This narrative review summarizes current evidence on the cardiovascular and kidney effects of GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide. Large randomized controlled trials have established reductions in major adverse cardiovascular events with several GLP-1 receptor agonists, while dedicated evidence for clinically meaningful chronic kidney disease progression is currently strongest for semaglutide. Cardiovascular benefits of semaglutide have also been demonstrated in individuals with overweight or obesity without type 2 diabetes, supporting effects beyond glucose lowering. Tirzepatide provides substantial improvements in glycemic control and body weight, with expanding evidence supporting cardiovascular benefit, including particularly encouraging findings in obesity-related heart failure with preserved ejection fraction. In contrast, its kidney evidence remains less mature and is derived predominantly from secondary and post-hoc analyses rather than from a dedicated kidney outcome trial. Collectively, these findings support a phenotype-oriented and multimodal role for incretin-based therapies in CKM syndrome management while highlighting important differences in the maturity of outcome evidence.
Related
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BibTeX
@article{kierzkowski2026beyond,
title = {{Beyond glycemic control: cardiovascular and kidney benefits of GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide: a narrative review}},
author = {Filip Kierzkowski and Wiktoria Skrzypek and Wiesław Bryl and Anna Paczkowska and Karolina Hoffmann},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1977433},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1977433/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond glycemic control: cardiovascular and kidney benefits of GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide: a narrative review
AU - Filip Kierzkowski
AU - Wiktoria Skrzypek
AU - Wiesław Bryl
AU - Anna Paczkowska
AU - Karolina Hoffmann
PY - 2026
DA - 2026/10/16
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1977433
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1977433/full
AB - Cardiovascular-kidney-metabolic (CKM) syndrome reflects the complex interplay among cardiovascular disease, chronic kidney disease, type 2 diabetes, and obesity. GLP-1 receptor agonists and tirzepatide have emerged as important therapeutic options within CKM syndrome, although the strength and maturity of evidence differ across individual agents and cardiovascular and kidney outcomes. This narrative review summarizes current evidence on the cardiovascular and kidney effects of GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide. Large randomized controlled trials have established reductions in major adverse cardiovascular events with several GLP-1 receptor agonists, while dedicated evidence for clinically meaningful chronic kidney disease progression is currently strongest for semaglutide. Cardiovascular benefits of semaglutide have also been demonstrated in individuals with overweight or obesity without type 2 diabetes, supporting effects beyond glucose lowering. Tirzepatide provides substantial improvements in glycemic control and body weight, with expanding evidence supporting cardiovascular benefit, including particularly encouraging findings in obesity-related heart failure with preserved ejection fraction. In contrast, its kidney evidence remains less mature and is derived predominantly from secondary and post-hoc analyses rather than from a dedicated kidney outcome trial. Collectively, these findings support a phenotype-oriented and multimodal role for incretin-based therapies in CKM syndrome management while highlighting important differences in the maturity of outcome evidence.
SN - 1664-2392
ER -