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2 "Hyewon Nam"
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Cardiovascular Risk/Epidemiology
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Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus
Seung Eun Lee, Hyewon Nam, Han Seok Choi, Hoseob Kim, Dae-Sung Kyoung, Kyoung-Ah Kim
Diabetes Metab J. 2022;46(4):567-577.   Published online February 8, 2022
  • 6,050 View
  • 370 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.


Citations to this article as recorded by  
  • Similar incidence of stroke with SGLT2 inhibitors and GLP-1 receptor agonists in real-world cohort studies among patients with type 2 diabetes
    André J. Scheen
    Diabetes Epidemiology and Management.2024; 13: 100179.     CrossRef
  • Diabetes and Stroke: Impact of Novel Therapies for the Treatment of Type 2 Diabetes Mellitus
    Inês Henriques Vieira, Tânia Santos Carvalho, Joana Saraiva, Leonor Gomes, Isabel Paiva
    Biomedicines.2024; 12(5): 1102.     CrossRef
  • Key results from observational studies and real‐world evidence of sodium‐glucose cotransporter‐2 inhibitor effectiveness and safety in reducing cardio‐renal risk
    Thomas Nyström
    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
  • Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
    Jung-Joon Cha, Soon Jun Hong, Subin Lim, Ju Hyeon Kim, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Do-Sun Lim, Jang Young Kim, Jin-Ok Jeong, Jeong-Hun Shin, Chi Young Shim, Jong-Young Lee, Young-Hyo Lim, Sung Ha Park, Eun Joo Cho, Hasung Kim, Jungkuk
    Korean Circulation Journal.2024;[Epub]     CrossRef
  • Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
    Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke ? Discordance between randomised controlled trials and observational studies
    André J. Scheen
    Diabetes & Metabolism.2023; 49(5): 101474.     CrossRef
Article image
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
  • 8,363 View
  • 408 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.


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    Biomedicines.2023; 11(8): 2292.     CrossRef
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    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
    Tiantian Han, Shaodi Ma, Chenyu Sun, Huimei Zhang, Guangbo Qu, Yue Chen, Ce Cheng, Eric L. Chen, Mubashir Ayaz Ahmed, Keun Young Kim, Raveena Manem, Mengshi Chen, Zhichun Guo, Hongru Yang, Yue Yan, Qin Zhou
    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
    Carlos K.H. Wong, David T.W. Lui, Angel Y.C. Lui, Ashley C.Y. Kwok, Marshall C.H. Low, Kristy T.K. Lau, Ivan C.H. Au, Xi Xiong, Matthew S.H. Chung, Eric H.Y. Lau, Benjamin J. Cowling
    Diabetes & Metabolism.2022; 48(1): 101307.     CrossRef
  • 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
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  • Glucose-Lowering Agents and COVID-19
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    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
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    Diabetologia.2021; 64(7): 1480.     CrossRef
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  • 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
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