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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
  • 36,967 View
  • 391 Download
  • 10 Web of Science
  • 7 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
  • Disease burden and symptom management in type 2 diabetic patients: A phenomenological study
    Sevgi Demir Çam, Sevda Uzun
    Public Health Nursing.2024; 41(6): 1291.     CrossRef
  • Comparing dual oral agents plus insulin vs. Triple oral agents in uncontrolled type II diabetes: A pilot study
    Nadia Gul, Inayat Ur Rehman, Yasar shah, Arbab Muhammad Ali, Zahid Ali, Omer Shehzad, Khang Wen Goh, Long Chiau Ming, Amal K. Suleiman, Nimesh Lageju
    PLOS ONE.2024; 19(11): e0311435.     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
Response
Response: Association between Diabetic Polyneuropathy and Chronic Complications in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:390-6)
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Diabetes Metab J. 2011;35(6):640-641.   Published online December 26, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.6.640
  • 2,924 View
  • 28 Download
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Original Articles
Association between Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Diabetes Metab J. 2011;35(4):390-396.   Published online August 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.4.390
  • 4,063 View
  • 39 Download
  • 11 Crossref
AbstractAbstract PDFPubReader   
Background

Diabetes mellitus is a major independent risk factor for cardiovascular disease (CVD), but high cardiovascular risk in diabetes mellitus patients is not completely explained by clustering traditional risk factors. Recently, associations between diabetic polyneuropathy (DPN) and macrovasculopathy have been suggested. We aimed to assess associations between DPN and cardiovascular complications in type 2 diabetic patients.

Methods

Microvascular and cardiovascular complications were evaluated in 1,041 type 2 diabetic patients.

Results

In patients with DPN, the age, prevalence of hypertension, diabetes duration, systolic blood pressure, pulse pressure, and hemoglobin glycation (HbA1c) levels were significantly higher, while the high density lipoprotein cholesterol (HDL-C) levels were lower than in those without DPN. The prevalence of CVD was higher in patients with DPN. In multivariate analysis, DPN was independently associated with CVD (odds ratio, 1.801; 95% confidence interval, 1.009 to 3.214).

Conclusion

Our results showed that DPN was associated with a high prevalence of cardiovascular disease in type 2 diabetic patients, but further studies are needed to investigate the causative nature of associations between DPN and CVD.

Citations

Citations to this article as recorded by  
  • Assessment of subclinical LV myocardial dysfunction in T2DM patients with diabetic peripheral neuropathy: a cardiovascular magnetic resonance study
    Xue-Ming Li, Ke Shi, Li Jiang, Jing Wang, Wei-Feng Yan, Yue Gao, Meng-Ting Shen, Rui Shi, Ge Zhang, Xiao-Jing Liu, Ying-Kun Guo, Zhi-Gang Yang
    Cardiovascular Diabetology.2024;[Epub]     CrossRef
  • The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes
    Tae Jung Oh, Han Song, Youngil Koh, Sung Hee Choi
    Endocrinology and Metabolism.2022; 37(2): 243.     CrossRef
  • Diabetic Peripheral Neuropathy Is Associated With Higher Systolic Blood Pressure in Adults With Type 2 Diabetes With and Without Hypertension in the Chinese Han Population
    Lingning Huang, Yongze Zhang, Yunmin Wang, Ximei Shen, Sunjie Yan
    Canadian Journal of Diabetes.2020; 44(7): 615.     CrossRef
  • Characterizing distal peripheral neuropathy in type 2 diabetes mellitus in a semi-urban community setting in Peru
    Meera F Iyengar, Antonio Bernabe-Ortiz
    Journal of Global Health Reports.2019;[Epub]     CrossRef
  • Cardiovascular disease predicts diabetic peripheral polyneuropathy in subjects with type 2 diabetes: A 10-year prospective study
    Juan Ybarra-Muñoz, Jeronimo Jurado-Campos, Maria Garcia-Gil, Edurne Zabaleta-del-Olmo, Teresa Mir-Coll, Adelaida Zabalegui, Josep Vidal, June H Romeo
    European Journal of Cardiovascular Nursing.2016; 15(4): 248.     CrossRef
  • Diabetic polyneuropathy and the risk of developing diabetic retinopathy: a nationwide, population‐based study
    I‐Chan Lin, Yuan–Hung Wang, Cheng‐Li Lin, Yen‐Jung Chang, Shwu‐Huey Lee, I‐Jong Wang
    Acta Ophthalmologica.2015; 93(8): 713.     CrossRef
  • Diabetic Peripheral Neuropathy in Ambulatory Patients with Type 2 Diabetes in a General Hospital in a Middle Income Country: A Cross-Sectional Study
    María de los Angeles Lazo, Antonio Bernabé-Ortiz, Miguel E. Pinto, Ray Ticse, German Malaga, Katherine Sacksteder, J. Jaime Miranda, Robert H. Gilman, Leighton R. James
    PLoS ONE.2014; 9(5): e95403.     CrossRef
  • The co-occurrence of myocardial dysfunction and peripheral insensate neuropathy in a streptozotocin-induced rat model of diabetes
    Maria N Marangoni, Scott T Brady, Shamim A Chowdhury, Mariann R Piano
    Cardiovascular Diabetology.2014;[Epub]     CrossRef
  • Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox
    Paulo Zoé Costa, Raquel Soares
    Life Sciences.2013; 92(22): 1037.     CrossRef
  • Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea
    Seung-Hyun Ko, Bong-Yun Cha
    Diabetes & Metabolism Journal.2012; 36(1): 6.     CrossRef
  • Epidemiology of Micro- and Macrovascular Complications of Type 2 Diabetes in Korea
    Jung Hee Kim, Dae Jung Kim, Hak Chul Jang, Sung Hee Choi
    Diabetes & Metabolism Journal.2011; 35(6): 571.     CrossRef
Chronic Complications in Adult Diabetic Patients with and without GAD Antibody.
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Korean Diabetes J. 2009;33(2):124-133.   Published online April 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.2.124
  • 2,422 View
  • 20 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Although the majority of diabetes mellitus (DM) patients diagnosed as adults have non-autoimmune forms of the disease, islet autoimmunity is encountered in some patients initially thought to have type 2 DM. The phenotype of DM patients with glutamic acid decarboxylase (GAD) antibodies is different from that of patients with GAD antibody-negative type 2 DM, with features such as relative leanness and hyperglycemia which may influence the development of complications. We sought to compare the prevalence of chronic complications in patients with and without the GAD antibody. METHODS: We recruited 427 patients (M: 218, F: 209) that were clinically diagnosed with type 2 DM after the age of 35 years. We measured GAD antibody and assessed the factors associated with chronic microvascular and macrovascular complications. RESULTS: Of these patients, 26 were GAD antibody-positive. The patients with GAD antibody had lower systolic blood pressure, higher high-density lipoprotein cholesterol value, and lower level of fasting and stimulated C-peptide than patients without GAD antibody (P < 0.05). Also, the patients with GAD antibody had lower prevalence of retinopathy compared with the patients without GAD antibody (19.2 vs. 47.9%; P < 0.05). The prevalence of nephropathy, peripheral neuropathy and cardiovascular autonomic neuropathy did not differ between the groups. In addition, the prevalence of coronary heart disease, cerebrovascular disease and peripheral arterial disease did not differ between the two groups. CONCLUSION: This study suggests that diabetic patients with GAD antibody have a lower risk for the development of retinopathy compared with patients without GAD antibody.

Citations

Citations to this article as recorded by  
  • Relationship between β-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults
    Tomislav Bulum, Marijana Vučić Lovrenčić, Jadranka Knežević Ćuća, Martina Tomić, Sandra Vučković-Rebrina, Lea Duvnjak
    Biomedicines.2023; 11(9): 2561.     CrossRef

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