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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
  • 35,348 View
  • 367 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
Letter
Editorial
Technology/Device
The Potential Role of MicroRNA in Diabetic Cardiomyopathy
Jin Hwa Kim
Diabetes Metab J. 2020;44(1):54-55.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0019
  • 3,635 View
  • 73 Download
  • 2 Web of Science
  • 2 Crossref
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Citations

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    Xiaokun Lou, Yuanyuan Zhang, Junfeng Guo, Lina Gao, Yingying Ding, Xinyu Zhuo, Qingqing Lei, Jing Bian, Rumei Lei, Wenyan Gong, Xingwei Zhang, Qibin Jiao
    Heart Failure Reviews.2023; 29(1): 1.     CrossRef
  • MiR-29a regulates cardiomyocyte apoptosis by targeting Bak1 in diabetic cardiomyopathy
    Xiaoyan Wang, Zhitao Zhang, Mei Wang
    The Journal of Biochemistry.2022; 171(6): 663.     CrossRef
Letters
Letter: Increased Serum Angiopoietin-Like 6 Ahead of Metabolic Syndrome in a Prospective Cohort Study (Diabetes Metab J 2019;43:521-9)
Jin Hwa Kim
Diabetes Metab J. 2019;43(5):727-728.   Published online October 24, 2019
DOI: https://doi.org/10.4093/dmj.2019.0172
  • 3,513 View
  • 34 Download
  • 1 Crossref
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Citations

Citations to this article as recorded by  
  • Angiopoietin-like proteins in atherosclerosis
    Yi-Zhang Liu, Chi Zhang, Jie-Feng Jiang, Zhe-Bin Cheng, Zheng-Yang Zhou, Mu-Yao Tang, Jia-Xiang Sun, Liang Huang
    Clinica Chimica Acta.2021; 521: 19.     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 Metab J. 2018;42(4):348-349.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0135
  • 3,368 View
  • 41 Download
  • 1 Crossref
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Citations

Citations to this article as recorded by  
  • PCSK9 gene participates in the development of primary dyslipidemias
    D Matías-Pérez, AD Pérez-Santiago, MA Sánchez Medina, JJ Alpuche Osorno, IA García-Montalvo
    Balkan Journal of Medical Genetics.2021; 24(1): 5.     CrossRef
Reviews
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
  • 5,798 View
  • 71 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   

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.

Citations

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  • Anti-inflammatory effect of glucagon-like Peptide-1 receptor agonist on the neurosensory retina in an acute optic nerve injury rat model
    Yeon Woong Chung, Ji Young Lee, Hyun Hee Ju, Jin A. Choi
    European Journal of Pharmacology.2022; 933: 175269.     CrossRef
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    Yang Liu, Zhaoxiang Yu, Yunlong Yang, Zhihan Lv
    Journal of Healthcare Engineering.2021; 2021: 1.     CrossRef
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    Doo Soo Jeon
    Cardiovascular Prevention and Pharmacotherapy.2020; 2(1): 11.     CrossRef
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    Ju-Ming Lu
    Advances in Therapy.2019; 36(4): 798.     CrossRef
  • A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes
    Irene Romera, Ana Cebrián-Cuenca, Fernando Álvarez-Guisasola, Fernando Gomez-Peralta, Jesús Reviriego
    Diabetes Therapy.2019; 10(1): 5.     CrossRef
  • 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
    The Journal of Korean Diabetes.2018; 19(1): 35.     CrossRef
Clinical Diabetes & Therapeutics
Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
Diabetes Metab J. 2017;41(5):367-373.   Published online October 24, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.367
  • 7,423 View
  • 220 Download
  • 7 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

Citations

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    Korean Journal of Family Medicine.2021; 42(4): 269.     CrossRef
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Clinical Diabetes & Therapeutics
Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon, Kyu-Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
Diabetes Metab J. 2017;41(5):357-366.   Published online October 24, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.357
  • 7,615 View
  • 150 Download
  • 17 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   

The Korean Diabetes Association (KDA) recently updated the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not changed from those of the 2015 KDA guidelines. The Committee on Clinical Practice Guidelines of the KDA has extensively reviewed and discussed the results of meta-analyses and systematic reviews of effectiveness and safety of OHAs and many clinical trials on Korean patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the patient's clinical characteristics and the efficacy, side effects, mechanism of action, risk of hypoglycemia, effect on body weight, patient preference, and combined comorbidity. In this review, we address the results of meta-analyses and systematic reviews, comparing the effectiveness and safety among OHAs. It will help to choose the appropriate drug for an individual patient with T2DM.

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Clinical Diabetes & Therapeutics
Monotherapy in Patients with Type 2 Diabetes Mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim
Diabetes Metab J. 2017;41(5):349-356.   Published online October 19, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.349
  • 5,644 View
  • 70 Download
  • 12 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   

In order to improve the quality of life and to prevent chronic complications related to diabetes mellitus, intensive lifestyle modification and proper medication are needed from the early stage of diagnosis of type 2 diabetes mellitus (T2DM). When using the first medication for diabetic patients, the appropriate treatment should be selected considering the clinical characteristics of the patient, efficacy of the drug, side effects, and cost. In general, the use of metformin as the first treatment for oral hypoglycemic monotherapy is recommended because of its excellent blood glucose-lowering effect, relatively low side effects, long-term proven safety, low risk of hypoglycemia, and low weight gain. If metformin is difficult to use as a first-line treatment, other appropriate medications should be selected in view of the clinical situation. If the goal of achieving glycemic control is not achieved by monotherapy, a combination therapy with different mechanisms of action should be initiated promptly.

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Clinical Diabetes & Therapeutics
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 Metab J. 2017;41(5):337-348.   Published online October 17, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.337
  • 7,107 View
  • 64 Download
  • 38 Web of Science
  • 45 Crossref
AbstractAbstract PDFPubReader   

In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.

Citations

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    Clinical Nursing Research.2022; 31(7): 1241.     CrossRef
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    Diabetes, Obesity and Metabolism.2022; 24(10): 2051.     CrossRef
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  • Increasing Individual Target Glucose Levels to Prevent Hypoglycemia in Patients with Diabetes
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    Korean Journal of Family Medicine.2021; 42(4): 269.     CrossRef
  • Phase III, randomized, double‐blind, placebo‐controlled study to evaluate the efficacy and safety of teneligliptin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise
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    Journal of Diabetes Investigation.2021; 12(4): 537.     CrossRef
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    Journal of Diabetes Investigation.2021; 12(9): 1594.     CrossRef
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    All Life.2021; 14(1): 333.     CrossRef
  • Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial
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    Research Journal of Pharmacy and Technology.2021; : 3471.     CrossRef
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    Diabetes & Metabolism Journal.2020; 44(2): 248.     CrossRef
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    Diabetes Care.2019; 42(11): 2057.     CrossRef
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  • Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
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Editorial
Complications
Serum Prolactin and Cardiac Remodeling in Subjects with Prediabetes
Jin Hwa Kim
Diabetes Metab J. 2017;41(3):168-169.   Published online June 21, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.3.168
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Letter
Letter: Effects of Rebamipide on Gastrointestinal Symptoms in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2016;40:240-7)
Jin Hwa Kim
Diabetes Metab J. 2016;40(4):334-335.   Published online August 18, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.4.334
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Diabetes Metab J : Diabetes & Metabolism Journal