Diabetes & Metabolism Journal

Original Articles

Pharmacotherapy
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

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Abstract PDF Supplementary Material PubReader 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.

Drug/Regimen
Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Sunir J. Garg, Kuan-Jen Chen, Je-Ho Kang, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang; Diabetes Metab J. 2023;47(3):394-404. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0221

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Background
To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care.
Methods
This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR.
Results
There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70).
Conclusion
Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

Citations

Citations to this article as recorded by

Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications
Ehsan Rahimy, Euna B. Koo, Karen M. Wai, Cassie A. Ludwig, Andrea L. Kossler, Prithvi Mruthyunjaya
American Journal of Ophthalmology.2025; 270: 93. CrossRef
Incretin‐based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta‐analysis of observational studies
Samuel Igweokpala, Naheemot Olaoluwa Sule, Antonios Douros, Oriana H. Y. Yu, Kristian B. Filion
Diabetes, Obesity and Metabolism.2024; 26(2): 721. CrossRef
Association of sodium–glucose cotransporter‐2 inhibitors and the risk of retinal vascular occlusion: A real‐world retrospective cohort study in Taiwan
Tzu‐Yi Lin, Eugene Yu‐Chuan Kang, Shih‐Chieh Shao, Edward Chia‐Cheng Lai, Nan‐Kai Wang, Sunir J. Garg, Kuan‐Jen Chen, Je‐Ho Kang, Wei‐Chi Wu, Chi‐Chun Lai, Yih‐Shiou Hwang
Diabetes/Metabolism Research and Reviews.2024;[Epub] CrossRef
Risk of rotator cuff tear and rotator cuff repair surgery comparison between sodium-glucose cotransporter 2 inhibitors and glucagon like peptide-1 receptor agonists: A real-world study
Yu-Chi Su, Pei-Chun Hsieh, Edward Chia-Cheng Lai, Yu-Ching Lin
Diabetes & Metabolism.2024; 50(2): 101522. CrossRef
Optimising renal risk parameters in type 2 diabetes mellitus: Perspectives from a retinal viewpoint
Sarita Jacob, George I. Varughese
Clinical Medicine.2024; 24(2): 100031. CrossRef
Risk of diabetic retinopathy and diabetic macular oedema with sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database
Aikaterini Eleftheriadou, David Riley, Sizheng S. Zhao, Philip Austin, Gema Hernández, Gregory Y. H. Lip, Timothy L. Jackson, John P. H. Wilding, Uazman Alam
Diabetologia.2024; 67(7): 1271. CrossRef
Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study
Karen M. Wai, Kapil Mishra, Euna Koo, Cassie Ann Ludwig, Ravi Parikh, Prithvi Mruthyunjaya, Ehsan Rahimy
American Journal of Ophthalmology.2024; 265: 39. CrossRef
Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy
Andrew J. Barkmeier, Jeph Herrin, Kavya Sindhu Swarna, Yihong Deng, Eric C. Polley, Guillermo E. Umpierrez, Rodolfo J. Galindo, Joseph S. Ross, Mindy M. Mickelson, Rozalina G. McCoy
Ophthalmology Retina.2024; 8(10): 943. CrossRef
Association Between Pentoxifylline Use and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multi-Institutional Cohort Study
Tzu-Yi Lin, Eugene Yu-Chuan Kang, Nan-Kai Wang, Je-Ho Kang, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang
Biomedical Journal.2024; : 100771. CrossRef
Association between sodium-glucose cotransporter 2 inhibitors and eye disorders: a systematic review and meta-analysis
Bo Xu, Bo Kang, Fan Tang, Jiecan Zhou, Zunbo He
Expert Review of Clinical Pharmacology.2024; 17(10): 949. CrossRef
Impact of glucagon‐like peptide‐1 receptor agonists on diabetic retinopathy: A meta‐analysis of clinical studies emphasising retinal changes as a primary outcome
Ishani Kapoor, Swara M. Sarvepalli, David A. D'Alessio, Majda Hadziahmetovic
Clinical & Experimental Ophthalmology.2024;[Epub] CrossRef
Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data
Masaya Koshizaka, Tomoaki Tatsumi, Fumiko Kiyonaga, Yoshinori Kosakai, Yoko Yoshinaga, Mami Shintani-Tachi
Diabetes Therapy.2024; 15(11): 2401. CrossRef
NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY
Rithwick Rajagopal, Janet B. McGill
Retina.2024; 44(11): 1851. CrossRef
SGLT2 inhibitors and diabetic retinopathy: Insights from the management of nephropathy
Maria S. Varughese, Lakshminarayanan Varadhan
Eye.2024;[Epub] CrossRef
Mechanism and therapeutic targets of circulating immune cells in diabetic retinopathy
Bowen Zhao, Yin Zhao, Xufang Sun
Pharmacological Research.2024; 210: 107505. CrossRef
Diabetes Renders Photoreceptors Susceptible to Retinal Ischemia-Reperfusion Injury
David A. Antonetti, Cheng-Mao Lin, Sumathi Shanmugam, Heather Hager, Manjing Cao, Xuwen Liu, Alyssa Dreffs, Adam Habash, Steven F. Abcouwer
Investigative Ophthalmology & Visual Science.2024; 65(13): 46. CrossRef
Multi-omics in exploring the pathophysiology of diabetic retinopathy
Xinlu Li, XiaoJing Dong, Wen Zhang, Zhizhou Shi, Zhongjian Liu, Yalian Sa, Li Li, Ninghua Ni, Yan Mei
Frontiers in Cell and Developmental Biology.2024;[Epub] CrossRef
Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Yih-Shiou Hwang
Diabetes & Metabolism Journal.2023; 47(4): 573. CrossRef
Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
Jihee Ko, Sun Joon Moon
Diabetes & Metabolism Journal.2023; 47(4): 571. CrossRef
Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes
Fu-Shun Yen, James Cheng-Chung Wei, Teng-Shun Yu, Yu-Tung Hung, Chih-Cheng Hsu, Chii-Min Hwu
JAMA Network Open.2023; 6(12): e2348431. CrossRef

Complications
Effect of the Glucagon-Like Peptide-1 Receptor Agonists on Autonomic Function in Subjects with Diabetes: A Systematic Review and Meta-Analysis: Carla Greco, Daniele Santi, Giulia Brigante, Chiara Pacchioni, Manuela Simoni; Diabetes Metab J. 2022;46(6):901-911. Published online April 12, 2022; DOI: https://doi.org/10.4093/dmj.2021.0314

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Background
In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes.
Methods
According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs).
Results
In the studies enrolled, HR significantly increased after treatment (P<0.001), whereas low frequency/high frequency ratio did not differ (P=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (P=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed.
Conclusion
The meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function.

Citations

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Heart and health behavior responses to GLP-1 receptor agonists: a 12-wk study using wearable technology and causal inference
Gregory J. Grosicki, Jeongeun Kim, Finn Fielding, Summer R. Jasinski, Christopher Chapman, William von Hippel, Kristen E. Holmes
American Journal of Physiology-Heart and Circulatory Physiology.2025; 328(2): H235. CrossRef
Liraglutide does not increase heart rate of diabetic patients during acute myocardial infarction
Qianyi Li, Chunxuan Wu, Shiqun Sun, Lingchao Yang, Yanyan Li, Yixin Niu, Li Zhang, Wei Li, Ying Yu
Journal of Diabetes.2024;[Epub] CrossRef
A randomized, double‐blind trial assessing the efficacy and safety of two doses of dulaglutide in Japanese participants with type 2 diabetes (AWARD‐JPN)
Tomoaki Morioka, Masakazu Takeuchi, Akichika Ozeki, Masanori Emoto
Diabetes, Obesity and Metabolism.2024; 26(8): 3167. CrossRef
Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management
Aikaterini Eleftheriadou, Vincenza Spallone, Abd A. Tahrani, Uazman Alam
Diabetologia.2024; 67(12): 2611. CrossRef
Autonomic Nervous System: A Therapeutic Target for Cardiac End-Organ Damage in Hypertension
Lisa A. Gottlieb, Felix Mahfoud, Stavros Stavrakis, Thomas Jespersen, Dominik Linz
Hypertension.2024; 81(10): 2027. CrossRef
Effect of the glucagon‐like peptide‐1 receptor agonists on diabetic peripheral neuropathy: A meta‐analysis
Shujin Fan, Yue Qiu, Jing Liu, Tianxin Zhu, Chuan Wang, Dan Liu, Li Yan, Meng Ren
Journal of Neurochemistry.2024;[Epub] CrossRef
Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics
Anthony J. Evans, Yu-Long Li
International Journal of Molecular Sciences.2024; 25(22): 12464. CrossRef
Hormonal Gut–Brain Signaling for the Treatment of Obesity
Eun Roh, Kyung Mook Choi
International Journal of Molecular Sciences.2023; 24(4): 3384. CrossRef
Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis
Yi-lin Huang, Xiao-zhuo Xu, Jing Liu, Pin-yao Wang, Xue-li Wang, Hong-lin Feng, Cheng-jiang Liu, Xu Han
BMC Cardiovascular Disorders.2023;[Epub] CrossRef
Obesity and hypertension: Obesity medicine association (OMA) clinical practice statement (CPS) 2023
Tiffany Lowe Clayton, Angela Fitch, Harold Edward Bays
Obesity Pillars.2023; 8: 100083. CrossRef
Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy
Jonathan Goldney, Jack A. Sargeant, Melanie J. Davies
Diabetologia.2023; 66(10): 1832. CrossRef
Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis
Susumu Z. Sudo, Tadeu L. Montagnoli, Bruna de S. Rocha, Aimeé D. Santos, Mauro P. L. de Sá, Gisele Zapata-Sudo
Biomedicines.2022; 10(12): 3258. CrossRef

Short Communication

Drug/Regimen
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study: Hwi Seung Kim, Taekwan Yoon, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2022;46(4):658-662. Published online November 8, 2021; DOI: https://doi.org/10.4093/dmj.2021.0232

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Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m², and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P<0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; P<0.001) after 1 year. Over 1 year, the bodyweight change was −2.8 kg (95% CI, −4.21 to −1.47; P<0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

Citations

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Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies
Aftab Ahmad, Hani Sabbour
Cardiovascular Diabetology.2024;[Epub] CrossRef
Sodium–Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome
Fernando Cortés-Camacho, Oscar René Zambrano-Vásquez, Elena Aréchaga-Ocampo, Jorge Ismael Castañeda-Sánchez, José Guillermo Gonzaga-Sánchez, José Luis Sánchez-Gloria, Laura Gabriela Sánchez-Lozada, Horacio Osorio-Alonso
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SGLT2i and GLP1RA effects in patients followed in a hospital diabetology consultation
António Cabral Lopes, Olga Lourenço, Manuel Morgado
Expert Review of Clinical Pharmacology.2024; 17(11): 1081. CrossRef
Hormonal Gut–Brain Signaling for the Treatment of Obesity
Eun Roh, Kyung Mook Choi
International Journal of Molecular Sciences.2023; 24(4): 3384. CrossRef
All‐cause mortality and cardiovascular outcomes with sodium‐glucose Co‐transporter 2 inhibitors, glucagon‐like peptide‐1 receptor agonists and with combination therapy in people with type 2 diabetes
David R. Riley, Hani Essa, Philip Austin, Frank Preston, Isatu Kargbo, Gema Hernández Ibarburu, Ramandeep Ghuman, Daniel J. Cuthbertson, Gregory Y. H. Lip, Uazman Alam
Diabetes, Obesity and Metabolism.2023; 25(10): 2897. CrossRef
The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
Chen Li, Jie Luo, Mingyan Jiang, Keke Wang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
Hwi Seung Kim, Woo Je Lee
Diabetes & Metabolism Journal.2022; 46(4): 665. CrossRef
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
Tomoyuki Kawada
Diabetes & Metabolism Journal.2022; 46(4): 663. CrossRef
Durability of glucose-lowering effect of dulaglutide in patients with type 2 diabetes mellitus: A real-world data study
Hwi Seung Kim, Yun Kyung Cho, Myung Jin Kim, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee
Frontiers in Endocrinology.2022;[Epub] CrossRef

Reviews

Complications
Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet: Vincenza Spallone; Diabetes Metab J. 2019;43(1):3-30. Published online November 2, 2018; DOI: https://doi.org/10.4093/dmj.2018.0259

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Abstract PDF PubReader

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.

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Exploring heart rate variability in polycystic ovary syndrome: implications for cardiovascular health: a systematic review and meta-analysis
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Predicting the dynamics of heart rate variability in patients with type 1 diabetes against improving glycemic control
N.O. Pertseva, K.I. Moshenets
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Neurophysiological assessment of peripheral neuropathy through whole plantar nerve conduction in type 2 diabetes mellitus and healthy control subjects
Dario Ricciardi, Raffaele Galiero, Vincenzo Todisco, Gioacchino Tedeschi, Giuseppe Loffredo, Alfredo Caturano, Luca Rinaldi, Giovanni Cirillo, Ferdinando Carlo Sasso
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INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2024; 20(4): 225. CrossRef
2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang
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Diabetologia.2024; 67(12): 2611. CrossRef
Prevalence of cardiovascular autonomic neuropathy in an admixed population of patients with type 1 diabetes. Lessons from a pioneer multicentre study in Brazil
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Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy
Triantafyllos Didangelos, Eleni Karlafti, Evangelia Kotzakioulafi, Parthena Giannoulaki, Zisis Kontoninas, Anastasia Kontana, Polykarpos Evripidou, Christos Savopoulos, Andreas L. Birkenfeld, Konstantinos Kantartzis
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Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics
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The impact of working night shifts on cardiac autonomic nervous regulation during the six-minute walk test in nurses
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BMC Nursing.2024;[Epub] CrossRef
D1S-Neuro Program: Frequency and Risk Factors for the Development of Diabetic Neuropathy in Pediatric Patients with Type 1 Diabetes Mellitus, a Single Center Study
Marco Piccoli, Joaquin Gutierrez de Rubalcava Doblas, Patrizia Furlan, Silvia Cocchio, Alessandro Zamberlan, Gloria Panzeri, Vincenzo Baldo, Carlo Moretti
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Mortality risk factors in newly diagnosed diabetic cardiac autonomic neuropathy
Bruce A. Chase, Sylwia Pocica, Roberta Frigerio, Katerina Markopoulou, Demetrius M. Maraganore, Navamon Aunaetitrakul, Alexander Epshteyn, Alexandru C. Barboi
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Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy
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Functional and morphometric assessment of small-fibre damage in late-onset hereditary transthyretin amyloidosis with polyneuropathy: the controversial relation between small-fibre-related symptoms and diagnostic test findings
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In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes: A cross‐sectional 68 Ga‐RGD‐PET study
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Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors
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Vinni Faber Rasmussen, Mathilde Thrysøe, Páll Karlsson, Esben Thyssen Vestergaard, Kurt Kristensen, Ann-Margrethe Rønholt Christensen, Jens Randel Nyengaard, Astrid Juhl Terkelsen, Christina Brock, Klaus Krogh
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Clinical Immunology.2023; 250: 109319. CrossRef
A Nonrandomized Trial of the Effects of Passive Simulated Jogging on Short-Term Heart Rate Variability in Type 2 Diabetic Subjects
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The Retinal Nerve Fiber Layer Thickness Is Associated with Systemic Neurodegeneration in Long-Term Type 1 Diabetes
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The Use of Empirical Mode Decomposition on Heart Rate Variability Signals to Assess Autonomic Neuropathy Progression in Type 2 Diabetes
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Topical Capsaicin for the Management of Painful Diabetic Neuropathy: A Narrative Systematic Review
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A three-month physical training program improves cardiovascular autonomic function in patients with metabolic syndrome with and without diabetes – a pilot study
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In Ischemic Heart Disease, Reduced Sensitivity to Pressure at the Sternum Accompanies Lower Mortality after Five Years: Evidence from a Randomized Controlled Trial
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Carvedilol improves heart rate variability indices, biomarkers but not cardiac nerve density in streptozotocin-induced T2DM model of diabetic cardiac autonomic neuropathy
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Cardiovascular autonomic neuropathy and incident diabetic kidney disease in patients with type 2 diabetes
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Kardiovaskuläre Risiken in der 4.–6. Lebensdekade mit Diabetes mellitus Typ 1
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Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants
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Comparison of Risk Assessment Strategies for Patients with Diabetes Mellitus and Stable Chest Pain: A Coronary Computed Tomography Angiography Study
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BOND study: a randomised double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy
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The relationship between vitamin B12 levels and electrocardiographic ventricular repolarization markers
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Clinical Diabetes & Therapeutics
Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association: Hyun Jin Kim, Seok O Park, Seung-Hyun Ko, Sang Youl Rhee, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Byung-Wan Lee, Jin Hwa Kim, Kyung Mook Choi; Diabetes Metab J. 2017;41(6):423-429. Published online December 19, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.6.423

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Abstract PDF PubReader

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.

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Islet Studies and Transplantation
An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass: Suk Chon, Jean-François Gautier; Diabetes Metab J. 2016;40(2):99-114. Published online April 25, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.2.99

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Abstract PDF PubReader

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.

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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
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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

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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.

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Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park
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Frontiers in Endocrinology.2022;[Epub] CrossRef
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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
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The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic β-Cells: Itaru Kojima, Yuko Nakagawa; Diabetes Metab J. 2011;35(5):451-457. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.451

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The sweet taste receptor is expressed in taste cells located in taste buds of the tongue. This receptor senses sweet substances in the oral cavity, activates taste cells, and transmits the taste signals to adjacent neurons. The sweet taste receptor is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. Recent studies have shown that this receptor is also expressed in the extragustatory system, including the gastrointestinal tract, pancreatic β-cells, and glucose-responsive neurons in the brain. In the intestine, the sweet taste receptor regulates secretion of incretin hormones and glucose uptake from the lumen. In β-cells, activation of the sweet taste receptor leads to stimulation of insulin secretion. Collectively, the sweet taste receptor plays an important role in recognition and metabolism of energy sources in the body.

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The Incretins and Pancreatic β-Cells: Use of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide to Cure Type 2 Diabetes Mellitus: Mi-Hyun Kim, Moon-Kyu Lee; Korean Diabetes J. 2010;34(1):2-9. Published online February 28, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.1.2

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Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide. The complications associated with T2DM result in increased mortality and financial cost for those affected. T2DM has long been known to be associated with insulin resistance in peripheral tissues and a relative degree of insulin deficiency. However, the concept that insulin secretion and insulin sensitivity are not linked through a hyperbolic relationship in T2DM has continuously been demonstrated in many clinical trials. Thus, in order to prevent and treat T2DM, it is necessary to identify the substance(s) that will improve the function and survival of the pancreatic β-cells in both normal and pathologic conditions, so that production and secretion of insulin can be enhanced. Incretin hormones, such as glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP), have been shown to lower the postprandial and fasting glucose and the glycated hemoglobin levels, suppress the elevated glucagon level, and stimulate glucose-dependent insulin synthesis and secretion. In this report, we will review the biological actions and mechanisms associated with the actions of incretin hormones, GLP-1 and GIP, on β-cell health and compare the differences between GLP-1 and GIP.

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