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Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19
Sang Youl Rhee, Jeongwoo Lee, Hyewon Nam, Dae-Sung Kyoung, Dong Wook Shin, Dae Jung Kim
Diabetes Metab J. 2021;45(2):251-259.   Published online March 5, 2021
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  • 405 Download
  • 33 Web of Science
  • 34 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM).
As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset.
Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682).
This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.


Citations to this article as recorded by  
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  • Efficacy and Safety of Sitagliptin in the Treatment of COVID-19
    Ehab Mudher Mikhael, Siew Chin Ong, Siti Maisharah Sheikh Ghadzi
    Journal of Pharmacy Practice.2023; 36(4): 980.     CrossRef
  • DPP-4 Inhibitors as a savior for COVID-19 patients with diabetes
    Snehasish Nag, Samanwita Mandal, Oindrila Mukherjee, Suprabhat Mukherjee, Rakesh Kundu
    Future Virology.2023; 18(5): 321.     CrossRef
  • Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis
    Sabrina Schlesinger, Alexander Lang, Nikoletta Christodoulou, Philipp Linnerz, Kalliopi Pafili, Oliver Kuss, Christian Herder, Manuela Neuenschwander, Janett Barbaresko, Michael Roden
    Diabetologia.2023; 66(8): 1395.     CrossRef
  • ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAAS dysregulation in severe cases
    Raquel Leão Neves, Jéssica Branquinho, Júlia Galanakis Arata, Clarissa Azevedo Bittencourt, Caio Perez Gomes, Michelle Riguetti, Gustavo Ferreira da Mata, Danilo Euclides Fernandes, Marcelo Yudi Icimoto, Gianna Mastroianni Kirsztajn, João Bosco Pesquero
    Inflammation Research.2023; 72(8): 1719.     CrossRef
  • Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis
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    Archives of Medical Research.2022; 53(2): 186.     CrossRef
  • Use of DPP4i reduced odds of clinical deterioration and hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: Propensity score analysis of a territory-wide cohort in Hong Kong
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  • Dipeptidyl peptidase-4 (DPP-IV) inhibitor was associated with mortality reduction in COVID-19 — A systematic review and meta-analysis
    Ahmad Fariz Malvi Zamzam Zein, Wilson Matthew Raffaello
    Primary Care Diabetes.2022; 16(1): 162.     CrossRef
  • Mortality and Severity in COVID-19 Patients on ACEIs and ARBs—A Systematic Review, Meta-Analysis, and Meta-Regression Analysis
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    Frontiers in Medicine.2022;[Epub]     CrossRef
  • Short- and long-term prognosis of glycemic control in COVID-19 patients with type 2 diabetes
    K Zhan, X Zhang, B Wang, Z Jiang, X Fang, S Yang, H Jia, L Li, G Cao, K Zhang, X Ma
    QJM: An International Journal of Medicine.2022; 115(3): 131.     CrossRef
  • Decreased circulating dipeptidyl peptidase-4 enzyme activity is prognostic for severe outcomes in COVID-19 inpatients
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    Biomarkers in Medicine.2022; 16(5): 317.     CrossRef
  • Management von Diabetespatienten in der COVID-19-Pandemie
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  • Glucose-Lowering Agents and COVID-19
    Ah Reum Khang
    The Journal of Korean Diabetes.2022; 23(1): 1.     CrossRef
  • The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis
    Yidan Chen, Xingfei Lv, Sang Lin, Mohammad Arshad, Mengjun Dai
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Drug-Disease Severity and Target-Disease Severity Interaction Networks in COVID-19 Patients
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  • Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology
    Alba Sebastián-Martín, Belén G. Sánchez, José M. Mora-Rodríguez, Alicia Bort, Inés Díaz-Laviada
    Biomedicines.2022; 10(8): 2026.     CrossRef
  • Anti-Diabetic Drugs GLP-1 Agonists and DPP-4 Inhibitors may Represent Potential Therapeutic Approaches for COVID-19
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    Endocrine, Metabolic & Immune Disorders - Drug Targets.2022; 22(6): 571.     CrossRef
  • Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control
    Niya Narayanan, Dukhabandhu Naik, Jayaprakash Sahoo, Sadishkumar Kamalanathan
    World Journal of Virology.2022; 11(6): 399.     CrossRef
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    Xiao-Ce Dai, Zhuo-Yu An, Zi-Yang Wang, Zi-Zhen Wang, Yi-Ren Wang
    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
  • Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis
    Sabrina Schlesinger, Manuela Neuenschwander, Alexander Lang, Kalliopi Pafili, Oliver Kuss, Christian Herder, Michael Roden
    Diabetologia.2021; 64(7): 1480.     CrossRef
  • Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications
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    European Geriatric Medicine.2021; 12(4): 725.     CrossRef
  • Cardiometabolic Therapy and Mortality in Very Old Patients With Diabetes Hospitalized due to COVID-19
    Jose Manuel Ramos-Rincón, Luis M Pérez-Belmonte, Francisco Javier Carrasco-Sánchez, Sergio Jansen-Chaparro, Mercedes De-Sousa-Baena, José Bueno-Fonseca, Maria Pérez-Aguilar, Coral Arévalo-Cañas, Marta Bacete Cebrian, Manuel Méndez-Bailón, Isabel Fiteni Me
    The Journals of Gerontology: Series A.2021; 76(8): e102.     CrossRef
  • Managing diabetes in diabetic patients with COVID: where do we start from?
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    Acta Diabetologica.2021; 58(11): 1441.     CrossRef
  • The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data
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    Heliyon.2021; 7(8): e07665.     CrossRef
  • Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19 (Diabetes Metab J 2021;45:251-9)
    Sang Youl Rhee
    Diabetes & Metabolism Journal.2021; 45(4): 619.     CrossRef
  • Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19 (Diabetes Metab J 2021;45:251-9)
    Guntram Schernthaner
    Diabetes & Metabolism Journal.2021; 45(4): 615.     CrossRef
  • COVID-19 and metabolic disease: mechanisms and clinical management
    Charlotte Steenblock, Peter E H Schwarz, Barbara Ludwig, Andreas Linkermann, Paul Zimmet, Konstantin Kulebyakin, Vsevolod A Tkachuk, Alexander G Markov, Hendrik Lehnert, Martin Hrabě de Angelis, Hannes Rietzsch, Roman N Rodionov, Kamlesh Khunti, David Hop
    The Lancet Diabetes & Endocrinology.2021; 9(11): 786.     CrossRef
  • Diabetes, Obesity, and COVID-19
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    The Journal of Korean Diabetes.2021; 22(3): 174.     CrossRef
  • Sunlight Exposure and Phototherapy: Perspectives for Healthy Aging in an Era of COVID-19
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    International Journal of Environmental Research and Public Health.2021; 18(20): 10950.     CrossRef
  • Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-
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    Kardiologiia.2021; 61(9): 20.     CrossRef
  • Association of clinical characteristics, antidiabetic and cardiovascular agents with diabetes mellitus and COVID-19: a 7-month follow-up cohort study
    Marzieh Pazoki, Fatemeh Chichagi, Azar Hadadi, Samira Kafan, Mahnaz Montazeri, Sina Kazemian, Arya Aminorroaya, Mehdi Ebrahimi, Haleh Ashraf, Mojgan Mirabdolhagh Hazaveh, Mohammad Reza Khajavi, Reza Shariat Moharari, Seyed Hamidreza Sharifnia, Shahrokh Ka
    Journal of Diabetes & Metabolic Disorders.2021; 20(2): 1545.     CrossRef
  • COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy
    Lingli Xie, Ziying Zhang, Qian Wang, Yangwen Chen, Dexue Lu, Weihua Wu
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
  • The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence
    Tianli Zhang, Xiang Tong, Shijie Zhang, Dongguang Wang, Lian Wang, Qian Wang, Hong Fan
    Frontiers in Pharmacology.2021;[Epub]     CrossRef
Present and Future of Digital Health in Diabetes and Metabolic Disease
Sang Youl Rhee, Chiweon Kim, Dong Wook Shin, Steven R. Steinhubl
Diabetes Metab J. 2020;44(6):819-827.   Published online December 23, 2020
  • 8,497 View
  • 252 Download
  • 18 Web of Science
  • 18 Crossref
AbstractAbstract PDFPubReader   ePub   
The use of information and communication technology (ICT) in medical and healthcare services goes beyond everyday life. Expectations of a new medical environment, not previously experienced by ICT, exist in the near future. In particular, chronic metabolic diseases such as diabetes and obesity, have a high prevalence and high social and economic burden. In addition, the continuous evaluation and monitoring of daily life is important for effective treatment and management. Therefore, the wide use of ICTbased digital health systems is required for the treatment and management of these diseases. In this article, we compiled a variety of digital health technologies introduced to date in the field of diabetes and metabolic diseases.


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    International Journal of Behavioral Medicine.2023;[Epub]     CrossRef
  • Exploring the underlying mechanisms of obesity and diabetes and the potential of Traditional Chinese Medicine: an overview of the literature
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  • Stakeholders’ Perceptions Regarding Digital Therapeutics Reimbursement in South Korea: Qualitative Study
    Boram Sim, Jin Han Ju, Byungsoo Kim, Jin Yong Lee
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    Hong-Yan Sun, Xiao-Yan Lin
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  • Psychoeducational Interventions in Children and Adolescents with Type-1 Diabetes: A Systematic Review
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  • Blood Pressure Monitoring as a Digital Health Tool for Improving Diabetes Clinical Outcomes: Retrospective Real-world Study
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    Journal of Medical Internet Research.2022; 24(2): e32923.     CrossRef
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Original Article
Clinical Care/Education
Impact of Continuous Care on Health Outcomes and Cost for Type 2 Diabetes Mellitus: Analysis Using National Health Insurance Cohort Database
Ji Hyun Nam, Changwoo Lee, Nayoung Kim, Keun Young Park, Jeonghoon Ha, Jaemoon Yun, Dong Wook Shin, Euichul Shin
Diabetes Metab J. 2019;43(6):776-784.   Published online October 21, 2019
  • 5,076 View
  • 73 Download
  • 14 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   

The objective of the study was to determine the impact of continuous care on health outcomes and cost of type 2 diabetes mellitus (T2DM) in Korea.


A nationwide retrospective, observational case-control study was conducted. Continuity of treatment was measured using Continuity of Care (COC) score. Information of all patients newly diagnosed with T2DM in 2004 was retrieved from the National Health Insurance database for the period of 2002 to 2013. The study examined 2,373 patients after applying exclusion criteria, such as for patients who died from conditions not related to T2DM. Statistical analyses were performed using frequency distribution, simple analysis (t-test and chi-squared test), and multi-method analysis (simple linear regression, logistic regression, and survival analysis).


The overall COC score was 0.8±0.24. The average incidence of diabetic complications was 0.39 per patient with a higher COC score, whereas it was 0.49 per patient with a lower COC score. In both survival and logistic analyses, patients who had high COC score were significantly less likely to have diabetic complications (hazard ratio, 0.69; 95% confidence interval, 0.54 to 0.88). The average medical cost was approximately 3,496 United States dollar (USD) per patient for patients with a higher COC score, whereas it was 3,973 USD per patient for patients with a lower COC score during the 2006 to 2013 period, with a difference of around 477 USD, which is statistically significant after adjusting for other factors (β=−0.152).


Continuity of care for diabetes significantly reduced health complications and medical costs from patients with T2DM.


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  • Relationship between continuity of care and clinical outcomes in patients with dyslipidemia in Korea: a real world claims database study
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  • Association Between Team-Based Continuity of Care and Risk of Cardiovascular Diseases Among Patients With Diabetes: A Retrospective Cohort Study
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    Ye Seul Yang, Kyungdo Han, Tae Seo Sohn, Nam Hoon Kim
    The Korean Journal of Internal Medicine.2021; 36(5): 1049.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal