BEYOND GLYCEMIC CONTROL AND WEIGHT REDUCTION: PLEIOTROPIC EFFECTS OF GLP-1 RECEPTOR AGONISTS ON HUMAN PHYSIOLOGY - A NARRATIVE REVIEW

Matylda Król; Aleksandra Woźniak; Aleksandra Straszewska; Patrycja Sobantka; Szymon Mokrzecki; Anna Mamach; Katarzyna Aleksandrowicz; Zofia Grodzka; Mateusz Meszka; Ewa Bełc; Karolina Brzezińska

doi:10.31435/ijitss.2(50).2026.6208

Authors

Matylda Król Copernicus Memorial Hospital, Pabianicka ST. 62, 93-513 Lodz, Poland https://orcid.org/0009-0000-7759-4933
Aleksandra Woźniak Norbert Barlicki University Clinical Hospital No. 1 in Łódź, Stefan Kopcinski 22 Street, 90-153: Łódź, Poland https://orcid.org/0009-0003-5382-1451
Aleksandra Straszewska Central Teaching Hospital of Medical University of Lodz, Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0003-6293-9689
Patrycja Sobantka Central Teaching Hospital of Medical University of Lodz, Poland https://orcid.org/0009-0004-3128-5181
Szymon Mokrzecki Norbert Barlicki University Clinical Hospital No. 1 in Łódź, Stefan Kopcinski 22 Street, 90-153: Łódź, Poland https://orcid.org/0009-0005-8228-2711
Anna Mamach Norbert Barlicki University Clinical Hospital No. 1 in Łódź, Stefan Kopciński 22 Street, 90-153: Łódź, Poland https://orcid.org/0009-0004-5934-8674
Katarzyna Aleksandrowicz Medical University of Lodz: Lodz, Łódź Voivodeship, Poland https://orcid.org/0009-0008-5935-8265
Zofia Grodzka Independent Public Health Care Complex named after Marshal Józef Piłsudski in Płońsk (SPZZOZ): Płońsk, Poland https://orcid.org/0009-0002-0904-810X
Mateusz Meszka Central Teaching Hospital of Medical University of Lodz, Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0001-6147-7000
Ewa Bełc Intern doctor, USK nr 2, Medical Univerity of Lodz, Żeromskiego ST. 113, 90-549 Lodz, Poland https://orcid.org/0009-0004-0224-8162
Karolina Brzezińska Medical University of Lodz: Lodz, Łódź Voivodeship, Poland https://orcid.org/0009-0008-4403-6060

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.6208

Keywords:

GLP-1 Receptor Agonists, Semaglutide, Tirzepatide, Cardiovascular Disease, Chronic Kidney Disease, MASLD, Neuroprotection

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as one of the most important therapeutic advances in the management of type 2 diabetes mellitus and obesity. Originally developed to enhance glucose-dependent insulin secretion and improve glycemic control, these agents have demonstrated a broad spectrum of effects extending beyond traditional metabolic indications. The widespread expression of GLP-1 receptors throughout multiple organ systems provides a biological basis for their pleiotropic actions, which include modulation of inflammatory, vascular, metabolic, and neurohormonal pathways. This narrative review summarizes current evidence regarding the systemic effects of GLP-1RAs beyond diabetes and obesity. Recent landmark clinical trials have demonstrated significant reductions in major adverse cardiovascular events, improvements in heart failure-related outcomes, and slower progression of chronic kidney disease. Emerging evidence also supports beneficial effects in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), with improvements observed in hepatic steatosis, inflammation, and fibrosis. In addition, growing interest has focused on the neuroprotective properties of GLP-1RAs, including their potential role in neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Modulation of central reward pathways has further raised the possibility of their application in addiction medicine. Additional findings suggest favorable effects in obesity-associated obstructive sleep apnea and reproductive disorders, particularly polycystic ovary syndrome. Observational studies have also explored potential associations with reduced cancer risk and healthy aging, although evidence in these areas remains preliminary. Despite their favorable safety profile and expanding clinical utility, several emerging indications require further validation through large randomized controlled trials. Overall, current evidence supports the view that GLP-1 receptor agonists should be regarded as multisystem therapeutic agents with clinically meaningful effects extending far beyond glycemic control and weight reduction, highlighting their potential to reshape the management of numerous chronic diseases.

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