Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Search

Page Path
HOME > Search
5 "Glucagon-like peptide-1 receptor agonists"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Reviews
Pharmacotherapy
Article image
Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
Jung A Kim, Hye Jin Yoo
Diabetes Metab J. 2025;49(4):525-541.   Published online July 1, 2025
DOI: https://doi.org/10.4093/dmj.2025.0242
  • 37,071 View
  • 1,439 Download
  • 13 Web of Science
  • 26 Crossref
AbstractAbstract PDFPubReader   ePub   
Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated considerable efficacy in the treatment of diabetes and obesity, it is essential to recognize that their use is associated with certain intrinsic risks that must not be disregarded. The incidence of adverse effects, particularly gastrointestinal complications, psychiatric disorders, and ocular problems, highlights the critical need for thorough patient assessment and continuous monitoring to ensure both the safety and effectiveness of treatment. Despite the possibility of adverse events, GLP-1 RAs continue to represent a crucial therapeutic modality for metabolic disturbances. This highlights the significance of ongoing research initiatives aimed at optimizing their safe utilization and refining current treatment protocols to improve patient outcomes. This review summarizes updated research findings regarding the adverse effects of GLP-1 RAs, their mechanisms of action, and guidelines for clinical application.

Citations

Citations to this article as recorded by  
  • Seizure recurrence after GLP‐1 receptor agonist initiation in adults with epilepsy
    Majd A. AbuAlrob, Abdullah Hussein, Rand Abdellatif, Adham Itbaisha, Khaled Zammar, Boulenouar Mesraoua
    Epilepsia.2026; 67(3): 1246.     CrossRef
  • Engineered exosomal delivery of semaglutide activates SIRT1–FOXO3a–miR-124 signaling and protects against cortical neuroinflammation
    Elsayed A. Elmorsy, Sameh Saber, Ahmed Y. Kira, Manal Mohamed Hatem, Mohammed Alorini, Suzan Awad AbdelGhany Morsy, Hamad Alsaykhan, Abdulaziz A. Alsalloom, Nahla B. Mohamed, Norah Suliman Alsoqih, Rabab S. Hamad, Youssef El-Sayed, Nagwa Mahmoud Ramadan,
    Journal of Drug Delivery Science and Technology.2026; 118: 108078.     CrossRef
  • Gastrointestinal Adverse Effects of GLP-1 and Dual GLP-1/GIP Receptor Agonists: A Comprehensive Update in Diabetic and Obese Populations
    Nimet Yılmaz, Mehmet Bastemir
    Diabetes, Metabolic Syndrome and Obesity.2026; Volume 19: 1.     CrossRef
  • Glucagon-Like Peptide-1 Receptor Agonists and Acute Pancreatitis: Current Evidence and Clinical Implications
    Kwang Hyun Chung, Jaihwan Kim
    The Korean Journal of Pancreas and Biliary Tract.2026; 31(1): 1.     CrossRef
  • Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review
    Claudia Reytor-González, Martín Campuzano-Donoso, Gerardo Sarno, Martha Montalvan, Raquel Horowitz, Gianluca Rossetti, Vincenzo Pilone, Luigi Barrea, Giovanna Muscogiuri, Luigi Schiavo, Daniel Simancas-Racines
    Nutrients.2026; 18(4): 553.     CrossRef
  • Oral Administration of Crocus sativus Tepals Extract Restores High‐Fat Diet‐Induced Gut Dysbiosis and Modulates Intestinal Inflammation and Hepatic Lipid Metabolism
    Biljana Bursać, Miloš Vratarić, Ljupka Gligorovska, Luisa Bellachioma, Ana Teofilović, Danijela Vojnović Milutinović, Camilla Morresi, Elisabetta Damiani, Tiziana Bacchetti, Ana Djordjevic
    BioFactors.2026;[Epub]     CrossRef
  • A Rare Case of Semaglutide-Associated Small Bowel Obstruction Complicated by Acute Kidney Injury Requiring Dialysis
    Suhasini Rallabandi, Mansi Sharma, Krishnamraju Kosuru, Rahul Kashyap
    Cureus.2026;[Epub]     CrossRef
  • The pancreatic signal of GLP‐1 receptor agonists: A biliary phenomenon rather than direct toxicity
    Andro Koren, Luciana Koren
    British Journal of Clinical Pharmacology.2026;[Epub]     CrossRef
  • Anti‐Obesity Pharmacotherapy and Emerging Multimodal Interventions for Obstructive Sleep Apnea
    Anish Preshy, Cornelius J. Fernandez, Mohammad Hamid Nedai, Joseph M. Pappachan
    Chronic Diseases and Translational Medicine.2026;[Epub]     CrossRef
  • Practical management of glucagon-like peptide-1 receptor agonists in gastroenterology: a position paper by the Italian Society of Gastroenterology (SIGE)
    Antonio Facciorusso, Edoardo G Giannini, Matteo Tacelli, Alberto Zanetto, Cristiano Spada, Ivo Boskoski, Manuele Furnari, Grazia Pennisi, Gabriele Capurso, Alessandro Vitello, Giovanni Marasco, Giovanni Sarnelli, Luca Frulloni, Marcello Maida
    Digestive and Liver Disease.2026;[Epub]     CrossRef
  • Adverse effects of GLP-1 receptor agonists: Clinical Implications, regulatory perspectives, and future directions
    Riad Mohammed Abdelrahman, Taha Hussein Musa, Ismail Adam Arbab, Eltieb Omer Ahmed, Sahar Ibrahim Gasmallah, Mohammed Jalal, Chiamaka Linda Mgbechidinma, Wafaa Ramadan Ahmed
    Obesity Medicine.2026; 61: 100699.     CrossRef
  • New generation anti-obesity drugs and bone health in postmenopausal women
    Jana Tomasová Studýnková
    Vnitřní lékařství.2026; 72(2): 104.     CrossRef
  • Re-establishing alliances: “Old Friends” confronting obesity, inflammation, and stress-related psychiatric disorders
    Luke W. Desmond, Christopher A. Lowry
    Brain Behavior and Immunity Integrative.2026; 15: 100166.     CrossRef
  • A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Limosilactobacillus fermentum K8-Lb1 Postbiotic on Weight Management and Metabolic Health Outcomes
    Ekaterina Papazova, Susanne Mitschke, Christiane Laue, Jürgen Schrezenmeir
    Nutrients.2026; 18(8): 1174.     CrossRef
  • Appetite Regulation and Gastric Emptying of Semaglutide in Non-Diabetic Obese Adults: A Systematic Review
    Uchechukwu Bethel Abioke, Isaac Baiden, Obiageri Ihuarulam Okeoma, Victoria Partey-Newman, Temitope Oluwatosin Adewale, Shadrach Oluchi Onyekezini, Ijeoma Linda Okwuowulu
    Epidemiology and Health Data Insights.2026; 2(3): ehdi035.     CrossRef
  • Assessment of knowledge, attitude, and practices towards the usage of antidiabetic drugs for weight loss among Lebanese population
    Dima Kreidieh, Rouba Ballout, Rana Abutaima, Samer A. Kharroubi, Fatima A. Saleh
    BMC Public Health.2026;[Epub]     CrossRef
  • A Narrative Review of Weight Management Strategies: From Lifestyle Interventions to Emerging Pharmacotherapies
    Iman Saad Ahmed, Sara Luay Tapponi, Hala Malek Manaa, Amina Soltani, Elzahraa Shehata Hussein, Fatemeh Ali Parvaresh, Zahid Hussain, Jasbir Arora (RSS)
    Journal of Obesity.2026;[Epub]     CrossRef
  • The case for primary prevention of obesity in the era of GLP-1 therapies
    Søren Holm, Manuel Tena-Sempere, Dimitrios Koutsouris, George V. Dedoussis, Karl-Heinz Wagner, Sara Arranz, Philippe Froguel, Torsten Bohn, Paulo J. Oliveira, Jeroen Lakerveld, Aakruti Kaikini, Achim Kramer, Adam Selamnia, Adina Weinberger, Adrian Jauch,
    The Lancet Regional Health - Europe.2026; : 101679.     CrossRef
  • Response to comment on “Efficacy and safety of GLP-1 receptor agonists in the management of obstructive sleep apnea in individuals without diabetes: A systematic review and meta-analysis of randomized, placebo-controlled trials”
    Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam
    Sleep Medicine.2025; 134: 106709.     CrossRef
  • Emerging Frontiers in GLP-1 Therapeutics: A Comprehensive Evidence Base (2025)
    Shikha Patel, Sarfaraz K. Niazi
    Pharmaceutics.2025; 17(8): 1036.     CrossRef
  • GLP-1 Receptor Agonists in Mood Disorders: A Psychiatric Perspective
    Pietro Carmellini, Alessandro Cuomo, Maria Beatrice Rescalli, Andrea Fagiolini
    Life.2025; 15(9): 1422.     CrossRef
  • Development of a risk prediction model for gastrointestinal adverse events associated with semaglutide administration in patients with type 2 diabetes mellitus
    Deyong Yue, Xuesheng Hua, Ling Zhu, Jun Wang, Lihua Gu, Zhengxia Yuan, Wenle Jian, Yirong Chen, Guoliang Meng
    Frontiers in Endocrinology.2025;[Epub]     CrossRef
  • Bridging Efficacy and Adherence in Glucagon-Like Peptide-1 Receptor Agonist Therapy: The Emerging Role of Oral Agents
    Sherry Yun Wang, Ryan Stofer, Hao Wang, Gregory A. Brent, Lu Shi, Yu Cai, Moom Roosan, Tannaz Moin
    Diabetes & Metabolism Journal.2025; 49(6): 1331.     CrossRef
  • Semaglutide from Bench to Bedside: The Experimental Journey Towards a Transformative Therapy for Diabetes, Obesity and Metabolic Liver Disorders
    Ralf Weiskirchen, Amedeo Lonardo
    Medical Sciences.2025; 13(4): 265.     CrossRef
  • Nutrient-Stimulated Hormone-Based Therapies: Transforming Obesity Management
    Ki Hoon Kwak, Chang Hee Jung
    Endocrinology and Metabolism.2025; 40(6): 879.     CrossRef
  • Research Progress of GLP-1 Receptor Agonists in the Treatment of Alzheimer’s Disease
    琳娜 勾
    Advances in Clinical Medicine.2025; 15(12): 2047.     CrossRef
Pharmacotherapy
Article image
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application
Jae Hyun Bae
Diabetes Metab J. 2025;49(3):386-402.   Published online May 1, 2025
DOI: https://doi.org/10.4093/dmj.2025.0220
  • 26,853 View
  • 1,620 Download
  • 27 Web of Science
  • 29 Crossref
AbstractAbstract PDFPubReader   ePub   
Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and significantly increases cardiovascular risk and mortality. Despite conventional therapies, including renin-angiotensin-aldosterone system inhibitors, substantial residual risk remains. The emergence of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists has reshaped DKD management. Beyond glycemic control, these agents provide distinct and complementary cardiorenal benefits through mechanisms such as hemodynamic modulation, anti-inflammatory effects, and metabolic adaptations. Landmark trials, including CREDENCE, DAPA-CKD, EMPA-KIDNEY, and FLOW, have demonstrated their efficacy in preserving kidney function and reducing adverse outcomes. SGLT2 inhibitors appear more effective in mitigating glomerular hyperfiltration and lowering heart failure risk, whereas GLP-1 receptor agonists are particularly beneficial in reducing albuminuria and atherosclerotic cardiovascular events. Although indirect comparisons suggest that SGLT2 inhibitors may offer greater protection against kidney function decline, direct head-to-head trials are lacking. Combination therapy holds promise, however further studies are needed to define optimal treatment strategies. This review synthesizes current evidence, evaluates comparative effectiveness, and outlines future directions in DKD management, emphasizing precision medicine approaches to enhance clinical outcomes. The integration of these therapies represents a paradigm shift in diabetes care, expanding treatment options for people with diabetes mellitus at risk of kidney failure.

Citations

Citations to this article as recorded by  
  • Trends in nephrology: kidney metabolism as a therapeutic target
    Jessica S Kleer, Markus M Rinschen
    Nephrology Dialysis Transplantation.2026; 41(2): 193.     CrossRef
  • Renoprotective effect of dulaglutide in L-NAME-induced hypertensive nephropathy in rats: insight into the roles of PPAR-gamma and VEGF
    Nermeen Bastawy, Aliaa E. M. K. El-Mosallamy, Rabab Ahmed Rasheed, A. S. Sadek, R. T. Khattab, Esraa Ali, Randa A. Zaghloul, Wael B. A. Ghaly, Amy F. Boushra
    Hypertension Research.2026; 49(3): 816.     CrossRef
  • Sodium‐glucose cotransporter 2 inhibitor ameliorates thiazolidinedione‐induced fluid retention through vascular leakage reduction in white adipose tissue
    Ji Yoon Kim, Hye‐Min Jang, Hye‐Jin Lee, Ah Hyeon Lee, Dong‐Hoon Kim, Sin Gon Kim, Nam Hoon Kim
    Diabetes, Obesity and Metabolism.2026; 28(3): 1764.     CrossRef
  • Age disparities in SGLT2 inhibitor prescription among people with type 2 diabetes: The role of frailty and sex
    Changyuan Yang, Petra Denig, Lynne Chepulis, Ryan G. Paul, Jung‐Im Shin, Ron T. Gansevoort, Priya Vart
    Diabetes, Obesity and Metabolism.2026; 28(3): 2265.     CrossRef
  • Diabetic kidney disease: integrating multi-omics insights, artificial intelligence, and novel therapeutics for precision medicine
    Tao Li, Kaili Chen, Yiting Sun, Linqi Zhang
    Frontiers in Genetics.2026;[Epub]     CrossRef
  • Nobiletin Ameliorated the Development of Diabetic Kidney Disease via Modulating Ferroptosis and Epithelial–Mesenchymal Transition Involving Gut–Kidney Axis
    Tingting Zhao, Chuyun Zhao, Qian Xiang, Xi Zhang, Kin-Fong Hong, Peiyu Liu, Zhongyan Sun, Yadi Liu, Ruiting Huang, Yiran Li, Hio-Fai Cheong, Yuwei Wu, Yingqiu Mo, Yiduo Xu, Yingxi Zhao, Qiruo Huang, Ying Xie, Youhua Xu
    The American Journal of Chinese Medicine.2026; 54(01): 303.     CrossRef
  • Bridging Innovation and Practice in Type 2 Diabetes Mellitus: Novel Antidiabetic Therapies and the Expanding Role of Community Pharmacists
    Marios Spanakis, Agapi Fournaraki, Frantzeska Nimee, Christos Kontogiorgis, Emmanouil K. Symvoulakis
    Pharmaceuticals.2026; 19(2): 271.     CrossRef
  • Diabetic kidney disease in northwest Ethiopia: Prevalence and determinants among adults with type 2 diabetes
    Workagegnehu Hailu, Tadesse Asmamaw Dejene, Markeshaw Tiruneh, Meseret Derbew Molla, Eshetie Melese Birru, Shitaye Alemu, Tadesse Awoke, Francesca D'Addio
    PLOS One.2026; 21(2): e0343210.     CrossRef
  • The Role of Non-Coding RNAs in the Pathogenesis and Progression of Diabetic Kidney Disease
    Yinfeng Guo, Yonghao Feng, Henglan Wu, Huanqing Gao
    International Journal of Molecular Sciences.2026; 27(5): 2352.     CrossRef
  • Association between cardiovascular-kidney-metabolic syndrome stages and risk of all-cause mortality in U.S. adults: a cross-sectional survey based on NHANES
    Yuanze Du, Wenxue Sun, Jiaqi Zhang, Jinfeng Wang, Kai Deng, Xiaowei Qiao, Jie Zhang, Xiaofang Zhang, Yueyuan Li, Xinyu Zhang, Xin Yang, Fangyu Cheng, Zongshuai Wang, Chunping Wang
    BMC Cardiovascular Disorders.2026;[Epub]     CrossRef
  • Integrated discovery of SBLR876: a potent RAGE inhibitor mitigating AGE–RAGE–NF-κB-mediated cytotoxicity and inflammation in diabetic kidney disease
    Mesfer Mohammad AL Shahrani, Mohammad Abohassan, Ayed A. Dera, Sivakumar Vijayaraghavalu, Prasanna Rajagopalan
    Biochemical and Biophysical Research Communications.2026; 811: 153540.     CrossRef
  • Glucagon-like peptide-1 receptor agonist and lupus nephritis in systemic lupus erythematosus with type 2 diabetes
    Muhammad Hanif, Jai S. Nagarajan, Ryan Murphy, Shiva P. Sah, Shuang Ye, Andras Perl, Cynthia C. Taub
    The American Journal of Medicine.2026;[Epub]     CrossRef
  • Impact of a structured nurse-delivered multi component SGLT2 inhibitor initiation and optimization pathway on kidney function and clinical outcomes in type 2 diabetes and chronic kidney disease: a real-world retrospective study
    Liang Huang, Yi Muhui
    BMC Nephrology.2026;[Epub]     CrossRef
  • Інгібітори натрій-глюкозного котранспортера 2-го типу в контексті кардіоренально-метаболічної коморбідності. Частина 2: метаболомічні аспекти нефропротекції
    Vira V. Zlatkina, Andriy O. Nesen, Nadiia V. Demikhova
    Ukrainian Journal of Nephrology and Dialysis.2026; (1(89)): 94.     CrossRef
  • Special Issue “Molecular Therapeutics for Diabetes and Related Complications”
    Kota V. Ramana
    International Journal of Molecular Sciences.2025; 26(12): 5585.     CrossRef
  • Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation
    Wenfeng Wang, Bi Ke, Chen Wang, Xiaojing Xiong, Xiuyuan Feng, Hua Yan
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular–Kidney–Metabolic Syndrome
    Aryan Gajjar, Arvind Kumar Raju, Amani Gajjar, Mythili Menon, Syed Asfand Yar Shah, Sourbha Dani, Andrew Weinberg
    Biomedicines.2025; 13(8): 1924.     CrossRef
  • Comparative analysis on renal and cardiovascular outcomes of antidiabetic treatment in chronic kidney disease patients—A systematic review and network meta‐analysis
    Peter Bramlage, Anjaly Vijayan, Treesa P. Varghese, Deepthy Melepurakkal Sadanandan, Stefanie Lanzinger, Carmen Ferrero Rodriguez
    Diabetes, Obesity and Metabolism.2025; 27(11): 6254.     CrossRef
  • Type 2 Diabetes and the Multifaceted Gut-X Axes
    Hezixian Guo, Liyi Pan, Qiuyi Wu, Linhao Wang, Zongjian Huang, Jie Wang, Li Wang, Xiang Fang, Sashuang Dong, Yanhua Zhu, Zhenlin Liao
    Nutrients.2025; 17(16): 2708.     CrossRef
  • Nutriomics and artificial intelligence nutrition obesity cohort (NAINOC): a design paper for a prospective cohort for nutrition and obesity research
    Minyoung Lee, Sungha Park, Soo-Hyun Park, Ho-Young Park, Yu Ra Lee, Min-Sun Kim, Miso Nam, Jangho Lee, Hyein Seo, Yong-ho Lee, Chan Joo Lee, Jae-Ho Park, Hye Hyun Yoo, Hyun-Jin Kim, Kyong-Oh Shin, Yoshikazu Uchida, Kyungho Park
    Clinical Hypertension.2025;[Epub]     CrossRef
  • Microvascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review of Retinopathy and Nephropathy Evidence
    Atia Arif, Sanu Lama, Bhavna Singla, Shivam Singla, Sunita Kumawat, Anusha Tharwani, Muhammad Usman, Hamna Khalid, Venkata Madusudana Rao Kanukollu, Osatohanmwen Ekomwereren, Shabir Khan
    Cureus.2025;[Epub]     CrossRef
  • Integrating UHPLC-QE-MS and Bioinformatics with Experimental Validation Reveals MAPK/FOS-Mediated Podocyte Apoptosis as the Key Mechanism of Alpiniae oxyphyllae and Saposhnikovia divaricata in Treating Diabetic Kidney Disease
    Xian Wang, Lin Zhang, Rongxin Tang, Wenlong Zhang, Yiqiang Xie, Kai Li
    Pharmaceuticals.2025; 18(10): 1449.     CrossRef
  • GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity
    Mark E. Cooper, Daniël H. van Raalte
    Journal of Clinical Investigation.2025;[Epub]     CrossRef
  • Short-Term Laboratory Outcomes of SGLT2 Inhibitor Use in Type 2 Diabetic Patients: A Retrospective Analysis
    Hamood AlSudais, Turky AlSulaiman, Badi A. Alotaibi, Abdulrahman Alshalani, Abdulaziz M. Almuqrin, Rehab B. Albakr, Jehad A. Aldali
    Journal of Clinical Medicine.2025; 14(22): 7985.     CrossRef
  • Chronic cardiorenal syndrome: cardio-renal protective effect of SGLT2i
    Yixin Zhu, Chenxi Lv, Hanqi Yang, Qian Lu, XuChen Wang, Yueqi Zhang, Maojuan Guo, Bo Yang
    Renal Failure.2025;[Epub]     CrossRef
  • FGF4-FGFR1 signaling promotes podocyte survival and glomerular function to ameliorate diabetic kidney disease in male mice
    Jie Zhou, Shuxin Wang, Jiaxin Lou, Beibin Pan, Min Zhao, Qian Li, Jing Zhou, Yali Du, Shuodan Ding, Meiling Yu, Jingjing Zhou, Xinwei Chen, Lingwei Jin, Xinyi Wang, Yepeng Hu, Zhe Wang, Xiaokun Li, Chao Zheng, Jian Sun, Zhifeng Huang
    Nature Communications.2025;[Epub]     CrossRef
  • Food‐Herb Dual‐Function in Astragali Radix‐Poria‐Rheum: Network Pharmacology and Database Mining for Diabetic Kidney Disease Mechanisms Exploration
    Meizi Wang, Weizhong Li, Qiong Cheng, Jiayu Sun, Cheng Cheng, Nana Wang, Ping Zhou, Min Zha, Yufeng Yang
    Food Science & Nutrition.2025;[Epub]     CrossRef
  • Інгібітори натрій-глюкозного котранспортера 2-го типу в контексті кардіоренально-метаболічної коморбідності. Частина 1: основи патофізіології та ключові клінічні дослідження
    Vira V. Zlatkina, Andriy O. Nesen, Nadiia V. Demikhova
    Ukrainian Journal of Nephrology and Dialysis.2025; (4(88)): 88.     CrossRef
  • GLP-1 Receptor Agonists and Blood Pressure: A State-of-the-Art Review of Mechanisms, Evidence, and Clinical Implications
    Areesha Moiz, Tetiana Zolotarova, Kristian B Filion, Mark J Eisenberg
    American Journal of Hypertension.2025;[Epub]     CrossRef
Basic and Translational Research
Article image
Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies
Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi
Diabetes Metab J. 2025;49(3):333-347.   Published online May 1, 2025
DOI: https://doi.org/10.4093/dmj.2025.0106
  • 10,153 View
  • 439 Download
  • 14 Web of Science
  • 19 Crossref
AbstractAbstract PDFPubReader   ePub   
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)—a key GLP-1RA target—mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

Citations

Citations to this article as recorded by  
  • Semaglutide beyond weight loss: Mechanistic insights and functional paradoxes from the SEMALEAN study
    Shambo S. Samajdar, Shashank Joshi
    Diabetes, Obesity and Metabolism.2026; 28(1): 779.     CrossRef
  • An expert narrative review on the brain-kidney axis in diabetic kidney disease: Mechanisms and therapeutic insights
    Zongrui Zhang, Rangzi Yi, Shihong Xiong, Yushu Zhang, Xuebin Cao, Wenqi Zhen, Yang Yang, Na Gong
    Diabetes Research and Clinical Practice.2026; 233: 113055.     CrossRef
  • Impaired Brain Incretin and Gut Hormone Expression in Human Alcohol-Related Brain Damage: Opportunities for Therapeutic Targeting
    Suzanne M. de la Monte, Ming Tong, Rolf I. Carlson, Greg Sutherland
    Biomolecules.2026; 16(1): 99.     CrossRef
  • Plasma GLP-1 (Glucagon-like Peptide-1) Depletion Is Correlated with Dysregulation of Adipocytokine in Type 2 Diabetic Patients With or Without Metabolic-Associated Fatty Liver Disease (MAFLD): A Cross-Sectional Study Related to Gender-Sex Disparities
    Houda Zoubiri, Wassila Saiah, Amel Otmane, Hamza Saidi, Mohamed Makrelouf, Samir Ait Abderrhmane, Ali El Mahdi Haddam, Elhadj-Ahmed Koceir
    International Journal of Molecular Sciences.2026; 27(3): 1218.     CrossRef
  • The Enterolimbic Axis: Gut-Brain Affective Circuits at the Crossroad of Metabolism, Emotion, and Behavior
    Antonio Gasbarrini, Francesca Sofia Galli, Gianluca Ianiro, Francesca Ponziani, Emanuele Rinninella
    American Journal of Gastroenterology.2026;[Epub]     CrossRef
  • Micronutrient Deficiencies in the Era of Second-Generation Incretin-Based Therapies for Obesity
    Andrijana Koceva, Andrej Janež, Tajda Pečko, Mojca Jensterle
    Nutrients.2026; 18(4): 677.     CrossRef
  • National Consensus on Semaglutide in Cardiology: From Clinical Evidence to Clinical Translation
    HK Chopra, Ashwani Mehta, CK Ponde, Navin C Nanda, GS Wander, Abraham Oomman, Prafulla Kerkar, SN Routray, GP Ratnaparkhi, Prashant Advani, Rituparna Shinde, Rajeev Agarwal, Ajay Mahajan, Jay Shah, Gaurav Verma, Sanjay Mittal, Dorairaj Prabhakar, D Ramesh
    Journal of The Association of Physicians of India.2026; 74(2): e8.     CrossRef
  • Polysaccharides from Acanthopanax senticosus (Rupr. et Maxim.) Harms: Molecular Messengers Linking the Traditional Efficacy of Fortifying the Spleen, Replenishing Qi, and Calming the Spirit to Gut-Immune Axis Regulation
    Bichun Hu, Deyong Zeng, Junli Liu, Weiping Wang, Shuaimin Hu, Weihong Lu
    Journal of Future Foods.2026;[Epub]     CrossRef
  • Obestatin: canonical and unexpected functions
    Icia Santos-Zas, Uxia Gurriaran-Rodriguez, Tania Cid-Diaz, Saul Leal-Lopez, Felipe F. Casanueva, Yolanda Pazos-Randulfe, Jesus P. Camiña
    Reviews in Endocrine and Metabolic Disorders.2026;[Epub]     CrossRef
  • The efficacy and safety of novel antidiabetic agents in polycystic ovary syndrome: a network meta-analysis
    Junjie Lin, Rongtao Yang, Jiacheng Zhuang, Wenbo Zhang, Qiang Tong, Jiahui Liu, Ye Kang, Yuan Yuan
    Journal of Ovarian Research.2026;[Epub]     CrossRef
  • Hypothalamus-liver talks: whispers in the language of metabolism
    Vitor Ferreira, Iara Fernández-González, Jane Jose Vattathara, Amanda Rodríguez-Díaz, Paola Fernández-Sanmartín, Carlos Diéguez
    Reviews in Endocrine and Metabolic Disorders.2026;[Epub]     CrossRef
  • Disproportionality Analysis of Tirzepatide vs. Semaglutide and Liraglutide: System Organ Class-Level Post-Marketing Reporting Patterns in EudraVigilance
    Ruxandra Cristina Marin, Cosmin Mihai Vesa, Delia Mirela Tit, Andrei-Flavius Radu, Gabriela S. Bungau
    International Journal of Molecular Sciences.2026; 27(7): 2988.     CrossRef
  • Hijacked Brain in Modern Obesity: Cue, Habit, Addiction, Emotion, and Restraint as Targets for Personalized Digital Therapy and Electroceuticals
    Taesung Lee, Seeun Park, Seokhyun Lee, Areum Hwangbo, HanGyeol Bae, Yumin Lee, Hyung Jin Choi
    Journal of Obesity & Metabolic Syndrome.2025; 34(3): 196.     CrossRef
  • Long-Term Efficacy Trajectories of GLP-1 Receptor Agonists: A Systematic Review and Network Meta-Analysis
    Zixuan Li, Zhoubo Han, Rong Sun, Xiuping Xuan, Chenghu Huang
    Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 3611.     CrossRef
  • The LEPR gene: A multifaceted regulator of energy homeostasis, obesity pathogenesis, and metabolic health
    Isar Sharma, Nishutosh, Kritika Bakshi, Ritu Mahajan, Nisha Kapoor
    Human Gene.2025; 46: 201486.     CrossRef
  • Glucagon-Like Peptide-1 Receptor Agonists Are Promising for the Treatment of Brain Diseases: an Outlook from the Perspective of Integrative Physiology
    N. V. Gulyaeva
    Journal of Evolutionary Biochemistry and Physiology.2025; 61(5): 1326.     CrossRef
  • Beyond Weight Loss: GLP-1 Usage and Appetite Regulation in the Context of Eating Disorders and Psychosocial Processes
    Isabel Krug, An Binh Dang, Jade Portingale, Yakun Li, Ying Qing Won
    Nutrients.2025; 17(23): 3735.     CrossRef
  • A personalized, evidence-based approach to obesity therapy using clinical algorithms: semaglutide or tirzepatide
    E. A. Troshina, M. B. Antsiferov, A. S. Ametov, G. R. Galstyan, T. N. Markova, T. I. Romantsova, N. V. Mazurina, O. M. Koteshkova
    Problems of Endocrinology.2025; 71(5): 19.     CrossRef
  • Tirzepatide and Obesity: A Narrative Review
    Arya Singh, Rahnuma Ahmad, Kona Chowdhury, Mahendra Narwaria, Mainul Haque
    Advances in Human Biology.2025;[Epub]     CrossRef
Original Article
Pharmacotherapy
Article image
Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus
Mijin Kim, Seung Chan Kim, Jinmi Kim, Bo Hyun Kim
Diabetes Metab J. 2025;49(1):49-59.   Published online October 24, 2024
DOI: https://doi.org/10.4093/dmj.2024.0105
  • 9,366 View
  • 409 Download
  • 13 Web of Science
  • 18 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes mellitus (T2DM) given their extra-pancreatic effects. However, there are concerns about carcinogenesis in the pancreas and thyroid gland. We aimed to evaluate the site-specific incidence of cancer in patients with T2DM-treated GLP-1 RAs using a nationwide cohort.
Methods
This study included data obtained from the Korean National Health Insurance Service (between 2004 and 2021). The primary outcome was newly diagnosed cancer, and the median follow-up duration for all participants was 8 years.
Results
After propensity score matching, 7,827 participants were analyzed; 2,609 individuals each were included in the GLP-1 RA, diabetes mellitus (DM) control, and non-DM control groups. The incidence rate ratio (IRR) of subsequent cancer in patients with T2DM was 1.73, which was higher than that of individuals without DM, and it increased in both men and women. Analysis of patients with T2DM showed no increased cancer risk associated with the use of GLP-1 RA, and similar results were observed in both men and women. The IRRs of pancreatic cancer (0.74), thyroid cancer (1.32), and medullary thyroid cancer (0.34) did not significantly increase in the GLP-1 RA group compared with those in the DM control group.
Conclusion
There was a 73% higher risk of cancer in patients with T2DM compared with the general population. However, among patients with T2DM, there was no association between the use of GLP-1 RAs and new-onset cancers, including pancreatic and medullary thyroid cancers.

Citations

Citations to this article as recorded by  
  • Implications of Glucagon-like Peptide-1 Receptor Agonists on Thyroid Function and Thyroid Nodules: A Drug Target Mendelian Randomization and Cohort Study
    Zhijun Zhang, Jingyun Yang, Ling Gao
    Endocrine Practice.2026; 32(1): 60.     CrossRef
  • Insulin resistance and metabolic dysfunction in thyroid nodules and differentiated thyroid cancer
    Stefano Iuliano, Maria Mirabelli, Stefania Giuliano, Antonio Brunetti
    Current Opinion in Oncology.2026; 38(1): 1.     CrossRef
  • Assessment of thyroid cancer risk associated with glucagon‐like peptide 1 receptor agonist use
    Tina Vilsbøll, Michael Stellfeld, Vanita R. Aroda, Sune Dandanell, Jens‐Peter David, Ceyda T. P. Kristiansen, Søren Rasmussen, Fiona L. Roberts, Laszlo Hegedüs
    Diabetes, Obesity and Metabolism.2026; 28(2): 1499.     CrossRef
  • Safety and Tolerability of Glucagon-Like Peptide-1 Receptor Agonists: A State-of-the-Art Narrative Review
    Setor K. Kunutsor, Samuel Seidu
    Drugs.2026; 86(1): 11.     CrossRef
  • Glucagon-like Peptide-1 Receptor Agonist Use and Pancreatic Cancer Risk in Patients with Chronic Pancreatitis
    Sarina Ailawadi, Jennifer E. Murphy, Michael H. Storandt, Amit Mahipal
    Cancers.2026; 18(2): 179.     CrossRef
  • Mechanisms in diabetes mellitus: Relationships to metabolism and/or neoplasia
    John A. D'Elia, Bijan Roshan, Larry A. Weinrauch
    Journal of Diabetes and its Complications.2026; 40(4): 109289.     CrossRef
  • Glucagon-like peptide-1 receptor agonists and the risk of obesity-related cancers: a systematic review and meta-analysis
    Yousef A. Ateiwi, Rahil Mahmood, Hon Jen Wong, Chen Ee Low, Chun En Yau, Ainsley Ryan Yan Bin Lee, Pei Chia Eng, Matilda Lee, Mark Y. Chan, Ching-Hui Sia
    Diabetes Research and Clinical Practice.2026; 234: 113158.     CrossRef
  • Practical management of glucagon-like peptide-1 receptor agonists in gastroenterology: a position paper by the Italian Society of Gastroenterology (SIGE)
    Antonio Facciorusso, Edoardo G Giannini, Matteo Tacelli, Alberto Zanetto, Cristiano Spada, Ivo Boskoski, Manuele Furnari, Grazia Pennisi, Gabriele Capurso, Alessandro Vitello, Giovanni Marasco, Giovanni Sarnelli, Luca Frulloni, Marcello Maida
    Digestive and Liver Disease.2026;[Epub]     CrossRef
  • GLP‐1 receptor agonists and the risk for cancer: A meta‐analysis of randomized controlled trials
    Giovanni Antonio Silverii, Christian Marinelli, Costanza Bettarini, Gloria Giovanna Del Vescovo, Matteo Monami, Edoardo Mannucci
    Diabetes, Obesity and Metabolism.2025; 27(8): 4454.     CrossRef
  • Evaluating Thyroid Cancer Risk in Glucagon-like Peptide-1 Analog Users With Thyroid Nodules
    Sanjana Balachandra, Rohma Syed, Zhixing Song, Julia Kasmirski, Andrea Gillis, Jessica Fazendin, Brenessa Lindeman, Herbert Chen
    Journal of Surgical Research.2025; 312: 104.     CrossRef
  • Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
    Jung A Kim, Hye Jin Yoo
    Diabetes & Metabolism Journal.2025; 49(4): 525.     CrossRef
  • Association between Cancer and Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review of Retrospective Cohort Studies
    Hyun Jin Park, Si Yoon Lee
    Research in Clinical Pharmacy.2025; 3(1): 28.     CrossRef
  • GLP-1 Receptor Agonists Initiation and Risk of Acute Pancreatitis and Pancreatic Cancer: A Real-World Comparative Study
    Omar Faour, Moheb Boktor, Hanford Yau, Mustafa Kinaan, Ishak A Mansi
    American Journal of Medicine Open.2025; 14: 100114.     CrossRef
  • Semaglutide and weight management in the Arab countries: Focus on the United Arab Emirates
    Sabina Semiz
    Health Sciences Review.2025; 17: 100244.     CrossRef
  • GLP-1 receptor agonists and cancer: current clinical evidence and translational opportunities for preclinical research
    Estefania Valencia-Rincón, Rajani Rai, Vishal Chandra, Elizabeth A. Wellberg
    Journal of Clinical Investigation.2025;[Epub]     CrossRef
  • GLP-1 Receptor Agonists in Solid Tumour Therapy: Exploring Their Anticancer Potential and Underlying Molecular Pathways
    Daniela Lucente, Stefania Bellino, Anna La Salvia
    Genes.2025; 16(11): 1352.     CrossRef
  • Bridging Efficacy and Adherence in Glucagon-Like Peptide-1 Receptor Agonist Therapy: The Emerging Role of Oral Agents
    Sherry Yun Wang, Ryan Stofer, Hao Wang, Gregory A. Brent, Lu Shi, Yu Cai, Moom Roosan, Tannaz Moin
    Diabetes & Metabolism Journal.2025; 49(6): 1331.     CrossRef
  • Joint Society Statement From the Society for Endocrinology (SfE), the British Thyroid Association (BTA) and the British Association of Endocrine and Thyroid Surgeons (BAETS) Regarding the Association of GLP‐1 Agonists and Thyroid Cancer
    Emma Watts, Jonathan Wadsley, Neil Sharma, Kristien Boelaert
    Clinical Endocrinology.2025;[Epub]     CrossRef
Review
The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea
Seungjoon Oh, Suk Chon, Kyu Jeong Ahn, In-Kyung Jeong, Byung-Joon Kim, Jun Goo Kang
Diabetes Metab J. 2015;39(3):177-187.   Published online June 15, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.3.177
  • 8,703 View
  • 63 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

Citations

Citations to this article as recorded by  
  • Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study
    Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park
    Diabetes & Metabolism Journal.2024; 48(3): 418.     CrossRef
  • Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy
    Youngsook Kim, Ji Hye Huh, Minyoung Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
    Diabetes & Metabolism Journal.2017; 41(5): 337.     CrossRef
  • Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
    The Korean Journal of Internal Medicine.2017; 32(6): 947.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer
TOP