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Original Article
Drug/Regimen
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon
Diabetes Metab J. 2021;45(5):675-683.   Published online August 12, 2020
DOI: https://doi.org/10.4093/dmj.2020.0107
  • 35,277 View
  • 366 Download
  • 9 Web of Science
  • 5 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

Citations to this article as recorded by  
  • Estimating Type 2 Diabetes Prevalence: A Model of Drug Consumption Data
    Rita Oliveira, Matilde Monteiro-Soares, José Pedro Guerreiro, Rúben Pereira, António Teixeira-Rodrigues
    Pharmacy.2024; 12(1): 18.     CrossRef
  • Efficacy and safety of enavogliflozin versus dapagliflozin added to metformin plus gemigliptin treatment in patients with type 2 diabetes: A double-blind, randomized, comparator-active study: ENHANCE-D study
    Kyung-Soo Kim, Kyung Ah Han, Tae Nyun Kim, Cheol-Young Park, Jung Hwan Park, Sang Yong Kim, Yong Hyun Kim, Kee Ho Song, Eun Seok Kang, Chul Sik Kim, Gwanpyo Koh, Jun Goo Kang, Mi Kyung Kim, Ji Min Han, Nan Hee Kim, Ji Oh Mok, Jae Hyuk Lee, Soo Lim, Sang S
    Diabetes & Metabolism.2023; 49(4): 101440.     CrossRef
  • Effectiveness and safety of teneligliptin added to patients with type 2 diabetes inadequately controlled by oral triple combination therapy: A multicentre, randomized, double‐blind, and placebo‐controlled study
    Minyoung Lee, Woo‐je Lee, Jae Hyeon Kim, Byung‐Wan Lee
    Diabetes, Obesity and Metabolism.2022; 24(6): 1105.     CrossRef
  • A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
    Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
    Diabetes, Obesity and Metabolism.2022; 24(9): 1800.     CrossRef
  • Glycaemic control with add‐on thiazolidinedione or a sodium‐glucose co‐transporter‐2 inhibitor in patients with type 2 diabetes after the failure of an oral triple antidiabetic regimen: A 24‐week, randomized controlled trial
    Jaehyun Bae, Ji Hye Huh, Minyoung Lee, Yong‐Ho Lee, Byung‐Wan Lee
    Diabetes, Obesity and Metabolism.2021; 23(2): 609.     CrossRef
Short Communication
Epidemiology
Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes
Sung Woo Kim, Jae-Han Jeon, Jun Sung Moon, Eon Ju Jeon, Mi-Kyung Kim, In-Kyu Lee, Jung Beom Seo, Keun-Gyu Park
Diabetes Metab J. 2019;43(5):718-726.   Published online March 19, 2019
DOI: https://doi.org/10.4093/dmj.2018.0222
  • 4,300 View
  • 51 Download
  • 2 Web of Science
AbstractAbstract PDFSupplementary MaterialPubReader   

Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

Response
Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
Sung Woo Kim, Keun-Gyu Park
Diabetes Metab J. 2018;42(4):350-352.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0138
  • 3,641 View
  • 38 Download
  • 4 Web of Science
  • 4 Crossref
PDFPubReader   

Citations

Citations to this article as recorded by  
  • Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Inversely Associated with N-Terminal Pro B-Type Natriuretic Peptide in Older Men and Women
    Francesco Spannella, Federico Giulietti, Roberta Galeazzi, Anna Passarelli, Serena Re, Chiara Di Pentima, Massimiliano Allevi, Paolo Magni, Riccardo Sarzani
    Biomedicines.2022; 10(8): 1961.     CrossRef
  • PCSK9: Associated with cardiac diseases and their risk factors?
    Yanan Guo, Binjie Yan, Shi Tai, Shenghua Zhou, Xi-Long Zheng
    Archives of Biochemistry and Biophysics.2021; 704: 108717.     CrossRef
  • Gut Lactobacillus Level Is a Predictive Marker for Coronary Atherosclerotic Lesions Progress and Prognosis in Patients With Acute Coronary Syndrome
    Jing Gao, Jie Wang, Li-Li Zhao, Ting-Ting Yao, Yang Chen, Jing Ma, Xu Zhang, Jing-Xian Wang, Yuan Wang, Zhuang Cui, Yin Liu
    Frontiers in Cellular and Infection Microbiology.2021;[Epub]     CrossRef
  • Butein Synergizes with Statin to Upregulate Low-Density Lipoprotein Receptor ThroughHNF1α-Mediated PCSK9 Inhibition in HepG2 Cells
    Jin-Taek Hwang, Hyo Jin Kim, Hyo-Kyoung Choi, Jae-Ho Park, Sangwon Chung, Min-Yu Chung
    Journal of Medicinal Food.2020; 23(10): 1102.     CrossRef
Original Article
Complications
Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome
Kwi-Hyun Bae, Sung Woo Kim, Yeon-Kyung Choi, Jung Beom Seo, Namkyun Kim, Chang-Yeon Kim, Won Kee Lee, Sungwoo Lee, Jung Guk Kim, In-Kyu Lee, Jang Hoon Lee, Keun-Gyu Park
Diabetes Metab J. 2018;42(3):207-214.   Published online May 2, 2018
DOI: https://doi.org/10.4093/dmj.2017.0081
  • 4,861 View
  • 54 Download
  • 25 Web of Science
  • 23 Crossref
AbstractAbstract PDFPubReader   
Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.

Methods

From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.

Results

Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.

Conclusion

Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

Citations

Citations to this article as recorded by  
  • Clinical Significance of PCSK9 and Soluble P-selectin in Predicting Major Adverse Cardiovascular Events After Primary Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome
    Yao Yao, Qining Qiu, Xiaoye Li, Zi Wang, Shikun Xu, Qianzhou Lv
    Cardiovascular Innovations and Applications.2024;[Epub]     CrossRef
  • Stratification in Heterozygous Familial Hypercholesterolemia: Imaging, Biomarkers, and Genetic Testing
    Pablo Corral, Carlos A. Aguilar Salinas, María Gabriela Matta, Valeria Zago, Laura Schreier
    Current Atherosclerosis Reports.2023; 25(12): 899.     CrossRef
  • Relationship of sortilin and proprotein convertase subtilisin/kexin type 9 in blood serum with the severity of carotid and coronary atherosclerosis in hypertensive patients
    Yu. Yu. Vukolova, I. V. Gubareva
    Russian Journal of Cardiology.2022; 27(2S): 4903.     CrossRef
  • PCSK9 Inhibition could be Effective for Acute Myocardial Infarction
    Baris Gencer, François Mach
    Current Medicinal Chemistry.2022; 29(6): 1016.     CrossRef
  • Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study
    Lina S. Silva-Bermúdez, Andrea Vargas-Villanueva, Carlos A. Sánchez-Vallejo, Ana C. Palacio, Andrés F. Buitrago, Carlos O. Mendivil
    Lipids in Health and Disease.2022;[Epub]     CrossRef
  • Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Inversely Associated with N-Terminal Pro B-Type Natriuretic Peptide in Older Men and Women
    Francesco Spannella, Federico Giulietti, Roberta Galeazzi, Anna Passarelli, Serena Re, Chiara Di Pentima, Massimiliano Allevi, Paolo Magni, Riccardo Sarzani
    Biomedicines.2022; 10(8): 1961.     CrossRef
  • Sex difference in circulating PCSK9 and its clinical implications
    Fang Jia, Si-Fan Fei, De-Bing Tong, Cong Xue, Jian-Jun Li
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall
    Yanan Guo, Binjie Yan, Yu Gui, Zhihan Tang, Shi Tai, Shenghua Zhou, Xi‐Long Zheng
    Journal of Cellular Physiology.2021; 236(4): 2333.     CrossRef
  • PCSK9 levels do not predict severity and recurrence of cardiovascular events in patients with acute myocardial infarction
    Marianne Zeller, Gilles Lambert, Michel Farnier, Maud Maza, Brice Nativel, Luc Rochette, Catherine Vergely, Yves Cottin
    Nutrition, Metabolism and Cardiovascular Diseases.2021; 31(3): 880.     CrossRef
  • Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction
    Jing Gao, Ya-Nan Yang, Zhuang Cui, Si-Yuan Feng, Jing Ma, Chang-Ping Li, Yin Liu
    Lipids in Health and Disease.2021;[Epub]     CrossRef
  • Circulating Biomarkers for Cardiovascular Disease Risk Prediction in Patients With Cardiovascular Disease
    Yuen-Kwun Wong, Hung-Fat Tse
    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
  • Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis
    Jiahui Liu, Fangfang Fan, Xingyu Luo, Wenjun Ji, Yaokun Liu, Yan Zhang, Bo Zheng
    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
  • PCSK9 in acute coronary syndrome: analysis of associations with clinical and laboratory characteristics
    Yu. A. Drenina, K. Yu. Nikolaev
    Cardiovascular Therapy and Prevention.2020; 19(4): 2484.     CrossRef
  • Relation of Proprotein Convertase Subtilisin/Kexin Type 9 to Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention
    Ik Jun Choi, Sungmin Lim, Dongjae Lee, Won Jik Lee, Kwan Yong Lee, Mi-Jeong Kim, Doo Soo Jeon
    The American Journal of Cardiology.2020; 133: 54.     CrossRef
  • A Narrative Review and Expert Panel Recommendations on Dyslipidaemia Management After Acute Coronary Syndrome in Countries Outside Western Europe and North America
    Ashraf Reda, Wael Almahmeed, Idit Dobrecky-Mery, Po-Hsun Huang, Ursulo Juarez-Herrera, Naresh Ranjith, Tobias Sayre, Miguel Urina-Triana
    Advances in Therapy.2020; 37(5): 1754.     CrossRef
  • PCSK9 concentrations in different stages of subclinical atherosclerosis and their relationship with inflammation
    Štefan Tóth, Peter Olexa, Zdenka Hertelyová, Peter Štefanič, Ivan Kopolovets, Peter Berek, Vladimir Filip, Ryan Chakravarty, Monika Široká, Daniel Pella
    Open Chemistry.2020; 18(1): 1011.     CrossRef
  • Association of serum proprotein convertase subtilisin/kexin type 9 with early atherosclerosis in newly diagnosed type 2 diabetes mellitus
    Wen Guo, Yingyun Gong, Jie Li, Pei Qin, Jing Lu, Xiaona Li, Wenfang Zhu, Nianzhen Xu, Hongwen Zhou, Qun Zhang
    Nutrition, Metabolism and Cardiovascular Diseases.2019; 29(8): 815.     CrossRef
  • PCSK9 and atherosclerosis burden in the coronary arteries of patients undergoing coronary angiography
    Yunes Panahi, Mohsen Sadeghi Ghahrodi, Mohsen Jamshir, Mohammad Amin Safarpour, Vanessa Bianconi, Matteo Pirro, Maryam Moshkani Farahani, Amirhossein Sahebkar
    Clinical Biochemistry.2019; 74: 12.     CrossRef
  • Association of PCSK9 plasma levels with metabolic patterns and coronary atherosclerosis in patients with stable angina
    Chiara Caselli, Serena Del Turco, Rosetta Ragusa, Valentina Lorenzoni, Michiel De Graaf, Giuseppina Basta, Arthur Scholte, Raffaele De Caterina, Danilo Neglia
    Cardiovascular Diabetology.2019;[Epub]     CrossRef
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    Massimiliano Ruscica, Lale Tokgözoğlu, Alberto Corsini, Cesare R. Sirtori
    Atherosclerosis.2019; 288: 146.     CrossRef
  • Letter: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
    Jin Hwa Kim
    Diabetes & Metabolism Journal.2018; 42(4): 348.     CrossRef
  • Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
    Sung Woo Kim, Keun-Gyu Park
    Diabetes & Metabolism Journal.2018; 42(4): 350.     CrossRef
  • Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population
    Gaojun Cai, Lei Yu, Zhiying Huang, Li Li, Xingli Fu
    Lipids in Health and Disease.2018;[Epub]     CrossRef

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