Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome

Ravić, Marko P.; Srejović, Ivan M.; Andjić, Marijana M.; Murić, Maja D.; Sretenović, Jasmina Z.; Jeremić, Nevena S.; Milosavljević, Isidora M.; Vuletić, Miona Lj.; Murić, Nemanja N.; Ravić, Katarina R.; Bolevich, Sergey B.; Sergeeva, Svetlana P.; Gorbunov, Alexander A.; Bolevich, Stefani S.; Jakovljević, Vladimir Lj.; Novaković, Jovana N.

doi:10.3390/medsci14050590

Open AccessArticle

Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome

by

Marko P. Ravić

^1,2

,

Ivan M. Srejović

^2,3,4,*

,

Marijana M. Andjić

^1,2,

Maja D. Murić

^2,3

,

Jasmina Z. Sretenović

^2,3

,

Nevena S. Jeremić

^1,2,5

,

Isidora M. Milosavljević

^1,2

,

Miona Lj. Vuletić

⁶,

Nemanja N. Murić

^7,8

,

Katarina R. Ravić

⁹,

Sergey B. Bolevich

¹⁰

,

Svetlana P. Sergeeva

¹⁰,

Alexander A. Gorbunov

⁴

,

Stefani S. Bolevich

^4,10,

Vladimir Lj. Jakovljević

^2,3,10,11

and

Jovana N. Novaković

^1,2

¹

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia

²

Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia

³

Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia

⁴

Department of Pharmacology, First Moscow State Medical University I.M. Sechenov, Trubetskaya Street 8, Str. 2, Moscow 119991, Russia

⁵

A.P. Neyubin Institute of Pharmacy, First Moscow State Medical University I.M. Sechenov, Moscow 119435, Russia

⁶

Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia

⁷

Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia

⁸

Psychiatric Clinic, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia

⁹

Department for Nuclear Medicine, University Clinical Center Kragujevac, 34000 Kragujevac, Serbia

¹⁰

Department of Pathophysiology, First Moscow State Medical University I.M. Sechenov, Moscow 119435, Russia

¹¹

Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina

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^*

Author to whom correspondence should be addressed.

Med. Sci. 2026, 14(5), 590; https://doi.org/10.3390/medsci14050590 (registering DOI)

Submission received: 3 August 2026 / Revised: 11 September 2026 / Accepted: 15 September 2026 / Published: 19 September 2026

(This article belongs to the Section Endocrinology and Metabolic Diseases)

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Abstract

Background/Objectives: Metabolic syndrome (MetS) increases susceptibility to myocardial ischemia/reperfusion (I/R) injury through metabolic disturbance, hypertension, and oxidative stress. This study aimed to compare the effects of liraglutide and semaglutide on post-ischemic cardiac function, oxidative stress, and histomorphological changes in rats with MetS. Methods: MetS was induced in male Wistar rats by a high-fat diet followed by low-dose streptozotocin. After confirmation of MetS, animals were treated with saline, liraglutide, or semaglutide for 6 weeks. Blood pressure, glycemia, oral glucose tolerance, and lipid profile were assessed during the protocol. In vivo cardiac function was evaluated by echocardiography, whereas ex vivo I/R injury was induced using the Langendorff technique. Cardiodynamic parameters, coronary flow, oxidative stress markers, and histological changes in the heart, liver, and pancreas were analyzed. Results: Both liraglutide and semaglutide improved the cardiometabolic profile of MetS rats, with semaglutide showing a more evident effect on body weight control. In the Langendorff model, both treatments improved post-ischemic recovery of myocardial contractility and relaxation during reperfusion. Treated animals also showed a more favorable oxidative stress profile, particularly lower superoxide anion levels and enhanced antioxidant defense. Histologically, both agents attenuated myocardial hypertrophy and collagen deposition, improved hepatic architecture by reducing inflammatory changes, and preserved pancreatic structure with less lipid accumulation and tissue injury. Conclusions: Liraglutide and semaglutide exerted significant cardioprotective and tissue-protective effects in experimental MetS complicated by myocardial I/R injury. These findings support their potential in limiting post-ischemic cardiac dysfunction and multiorgan damage in metabolically compromised conditions.

Keywords: metabolic syndrome; myocardial ischemia/reperfusion; cardioprotection; liraglutide; semaglutide; cardiac remodeling; oxidative stress

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MDPI and ACS Style

Ravić, M.P.; Srejović, I.M.; Andjić, M.M.; Murić, M.D.; Sretenović, J.Z.; Jeremić, N.S.; Milosavljević, I.M.; Vuletić, M.L.; Murić, N.N.; Ravić, K.R.; et al. Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome. Med. Sci. 2026, 14, 590. https://doi.org/10.3390/medsci14050590

AMA Style

Ravić MP, Srejović IM, Andjić MM, Murić MD, Sretenović JZ, Jeremić NS, Milosavljević IM, Vuletić ML, Murić NN, Ravić KR, et al. Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome. Medical Sciences. 2026; 14(5):590. https://doi.org/10.3390/medsci14050590

Chicago/Turabian Style

Ravić, Marko P., Ivan M. Srejović, Marijana M. Andjić, Maja D. Murić, Jasmina Z. Sretenović, Nevena S. Jeremić, Isidora M. Milosavljević, Miona Lj. Vuletić, Nemanja N. Murić, Katarina R. Ravić, and et al. 2026. "Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome" Medical Sciences 14, no. 5: 590. https://doi.org/10.3390/medsci14050590

APA Style

Ravić, M. P., Srejović, I. M., Andjić, M. M., Murić, M. D., Sretenović, J. Z., Jeremić, N. S., Milosavljević, I. M., Vuletić, M. L., Murić, N. N., Ravić, K. R., Bolevich, S. B., Sergeeva, S. P., Gorbunov, A. A., Bolevich, S. S., Jakovljević, V. L., & Novaković, J. N. (2026). Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome. Medical Sciences, 14(5), 590. https://doi.org/10.3390/medsci14050590

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Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome

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