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Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis
Ji Soo Kim, Gyeongsil Lee, Kyung-Il Park, Seung-Won Oh
Diabetes Metab J. 2024;48(2):312-320.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2022.0421
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments.
Methods
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks.
Results
Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], –0.17; 95% confidence interval [CI], –0.27 to –0.07). In the network meta- analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively.
Conclusion
SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by  
  • Sodium-glucose cotransporter protein 2 inhibition, plasma proteins, and ischemic stroke: A mediation Mendelian randomization and colocalization study
    Zhiqing Chen, Hongmei Meng, Yujin Guo, Huaiyu Sun, Wuqiong Zhang, Yu Guo, Shuai Hou
    Journal of Stroke and Cerebrovascular Diseases.2025; 34(1): 108136.     CrossRef
  • SGLT2 Inhibitors and GLP-1 Agonists: A Beacon of Hope for Stroke Prevention in Diabetes
    Jae-Han Jeon
    Diabetes & Metabolism Journal.2024; 48(2): 213.     CrossRef
  • Reply to comment on: Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyser database
    Wolfgang Rathmann, Karel Kostev
    Acta Diabetologica.2024; 61(8): 1081.     CrossRef
  • Empagliflozin: Primus Inter Pares Among Sodium–Glucose Cotransporter-2 Inhibitors?
    Giuseppe Biondi-Zoccai, Giacomo Frati, Mariangela Peruzzi, George W. Booz
    Journal of Cardiovascular Pharmacology.2024; 84(3): 271.     CrossRef
  • Impact of GLP-1 Receptor Agonists on Psoriasis and Cardiovascular Comorbidities: A Narrative Review
    Kathryn Haran, Chandler Johnson, Payton Smith, Zoë Venable, Allison Kranyak, Tina Bhutani, Caleb Jeon, Wilson Liao
    Psoriasis: Targets and Therapy.2024; Volume 14: 143.     CrossRef
Drug Regimen
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The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study
Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won
Diabetes Metab J. 2023;47(6):818-825.   Published online November 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0171
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Citations

Citations to this article as recorded by  
  • Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes
    Ji-Kui Wang, Di Zhang, Jin-Feng Wang, Wan-Lin Lu, Jing-Yuan Wang, Shi-Feng Liang, Ran Liu, Jing-Xin Jiang, Hong-Tao Li, Xuan Yang
    World Journal of Diabetes.2025;[Epub]     CrossRef
  • Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
    Il Rae Park, Jun Sung Moon
    Diabetes & Metabolism Journal.2024; 48(3): 387.     CrossRef
  • Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials
    Aman Goyal, Muhammad Daoud Tariq, Hritvik Jain, Abhigan Babu Shrestha, Laveeza Fatima, Romana Riyaz, Hritik Raj Yadav, Darsh Safi, Abdul Qahar K. Yasinzai, Rozi Khan, Amir Humza Sohail, Mohamed Daoud, Abu Baker Sheikh
    Cardiovascular Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis
    Lingyan Liu, Yongkun Deng, Lei Li, Xingbiao Yang, Zhaoheng Yin, Yong Lai, Jaspinder Kaur
    PLOS ONE.2024; 19(11): e0310696.     CrossRef
Drug Regimen
Article image
Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension
Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon
Diabetes Metab J. 2023;47(6):808-817.   Published online September 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0387
  • 4,490 View
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study
    In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo
    Diabetes, Obesity and Metabolism.2024; 26(11): 5065.     CrossRef
Brief Report
Drug/Regimen
Article image
Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus
Soon-Jib Yoo, Sang-Ah Chang, Tae Seo Sohn, Hyuk-Sang Kwon, Jong Min Lee, Sungdae Moon, Pieter Proot, Päivi M Paldánius, Kun Ho Yoon
Diabetes Metab J. 2021;45(6):954-959.   Published online November 12, 2020
DOI: https://doi.org/10.4093/dmj.2020.0173
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

Citations

Citations to this article as recorded by  
  • Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
    Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon
    Diabetes & Metabolism Journal.2024; 48(5): 915.     CrossRef
  • 2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
    Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
    Diabetes & Metabolism Journal.2023; 47(5): 575.     CrossRef
  • 2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
    Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
    Diabetes & Metabolism Journal.2021; 45(4): 461.     CrossRef
Review
Metabolic Risk/Epidemiology
Article image
Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming
Soung Won Jeong
Diabetes Metab J. 2020;44(5):640-657.   Published online October 21, 2020
DOI: https://doi.org/10.4093/dmj.2020.0115
  • 13,454 View
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  • 17 Web of Science
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AbstractAbstract PDFPubReader   ePub   
The worldwide prevalence of non-alcoholic fatty liver disease is around 25%, and that of nonalcoholic steatohepatitis (NASH) ranges from 1.5% to 6.45%. Patients with NASH, especially those with fibrosis, are at higher risk for adverse outcomes such as cirrhosis and liver-related mortality. Although vitamin E, pioglitazone, and liraglutide improved liver histology in randomized trials, there are currently no Food and Drug Administration-approved drugs for NASH. Five pharmacologic agents—obeticholic acid, elafibranor, cenicriviroc, resmetirom, and aramchol—are being evaluated in large, histology-based phase 3 trials. Within 2 to 4 years, new and effective drugs for the treatment of NASH are expected. Additionally, many phase 2 trials are ongoing for various agents. Based on the results of phase 2 and 3 trials, combination treatments are also being investigated. Future treatment strategies will comprise drug combinations and precision medicine based on the different phenotypes of NASH and treatment response of the individual patient.

Citations

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  • Recent Progresses on Pathophysiology, Diagnosis, Therapeutic Modalities, and Management of Non-alcoholic Fatty Liver Disorder
    Mahdi Barazesh, Sajad Jalili, Morteza Akhzari, Fouzieyeh Faraji, Ebrahim Khorramdin
    Current Drug Therapy.2024; 19(1): 20.     CrossRef
  • Ameliorative role of bioactive phytoconstituents targeting obesity associated NAFLD by modulation of inflammation and lipogenesis pathways: a comprehensive review
    Pervej Alom Barbhuiya, Saikat Sen, Manash Pratim Pathak
    Phytochemistry Reviews.2024; 23(4): 969.     CrossRef
  • Update on the clinical applications of SGLTis: Insight to benefits beyond hypoglycemic and cardiorenal protection
    Shibing Tao, Shanlan Guo, Nanwei Tong
    Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy.2024; 44(8): 642.     CrossRef
  • Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
    Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
    Diabetes & Metabolism Journal.2023; 47(2): 220.     CrossRef
  • Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis
    Hye Jin Chun, Eun Ran Kim, Minyoung Lee, Da Hyun Choi, Soo Hyun Kim, Eugene Shin, Jin-Hong Kim, Jin Won Cho, Dai Hoon Han, Bong-Soo Cha, Yong-ho Lee
    Metabolism.2023; 145: 155612.     CrossRef
  • Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study
    Willy B Theel, Bianca M Boxma-de Klerk, Femme Dirksmeier-Harinck, Elisabeth FC van Rossum, Danny A Kanhai, Jan A Apers, Bas M van Dalen, Robert J De Knegt, Bojou Neecke, Ellen M van der Zwan, Diederick E Grobbee, Thomas Hankemeier, Janneke Wiebolt, Manuel
    BMJ Open.2023; 13(7): e070431.     CrossRef
  • Inflammatory and fibrotic mechanisms in NAFLD—Implications for new treatment strategies
    Youngmin A. Lee, Scott L. Friedman
    Journal of Internal Medicine.2022; 291(1): 11.     CrossRef
  • Efficacy and safety of evogliptin in patients with type 2 diabetes and non‐alcoholic fatty liver disease: A multicentre, double‐blind, randomized, comparative trial
    Eugene Han, Ji Hye Huh, Eun Y. Lee, Ji C. Bae, Sung W. Chun, Sung H. Yu, Soo H. Kwak, Kyong S. Park, Byung‐Wan Lee
    Diabetes, Obesity and Metabolism.2022; 24(4): 752.     CrossRef
  • Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
    Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
    Obesity.2022; 30(6): 1279.     CrossRef
  • Thyroid diseases and new approaches for their treatment
    E. A. Fokina, A. O. Shpakov
    The Siberian Journal of Clinical and Experimental Medicine.2022; 37(3): 90.     CrossRef
  • Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction
    Giang Nguyen, So Young Park, Dinh Vinh Do, Dae-Hee Choi, Eun-Hee Cho
    Endocrinology and Metabolism.2022; 37(6): 918.     CrossRef
  • Inhibition of 11β-hydroxysteroid dehydrogenase 1 relieves fibrosis through depolarizing of hepatic stellate cell in NASH
    Su-Yeon Lee, Sanghwa Kim, Inhee Choi, Yeonhwa Song, Namjeong Kim, Hyung Chul Ryu, Jee Woong Lim, Hyo Jin Kang, Jason Kim, Haeng Ran Seo
    Cell Death & Disease.2022;[Epub]     CrossRef
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    Joel Yeh Siang Chen, Damien Chua, Carissa Odelia Lim, Wan Xi Ho, Nguan Soon Tan
    International Journal of Molecular Sciences.2022; 24(1): 158.     CrossRef
  • Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC
    Hyunmi Kim, Da Som Lee, Tae Hyeon An, Hyun-Ju Park, Won Kon Kim, Kwang-Hee Bae, Kyoung-Jin Oh
    International Journal of Molecular Sciences.2021; 22(9): 4495.     CrossRef
  • Allopurinol ameliorates high fructose diet induced hepatic steatosis in diabetic rats through modulation of lipid metabolism, inflammation, and ER stress pathway
    In-Jin Cho, Da-Hee Oh, Jin Yoo, You-Cheol Hwang, Kyu Jeung Ahn, Ho-Yeon Chung, Soung Won Jeong, Ju-Young Moon, Sang-Ho Lee, Sung-Jig Lim, In-Kyung Jeong
    Scientific Reports.2021;[Epub]     CrossRef
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    João Remí de Freitas Júnior, Igor Braga Ribeiro, Diogo Turiani Hourneaux de Moura, Vitor Massaro Takamatsu Sagae, Gabriel Mayo Vieira de Souza, Guilherme Henrique Peixoto de Oliveira, Sergio A Sánchez-Luna, Thiago Ferreira de Souza, Eduardo Turiani Hourne
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  • The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease
    Branka Filipovic, Snezana Lukic, Dragana Mijac, Marija Marjanovic-Haljilji, Marko Vojnovic, Jelena Bogdanovic, Tijana Glisic, Natasa Filipovic, Jamal Al Kiswani, Aleksandra Djokovic, Suncica Kapor, Slobodan Kapor, Zoran Bukumiric, Ana Starcevic
    International Journal of Molecular Sciences.2021; 22(24): 13219.     CrossRef
Original Articles
Drug/Regimen
Article image
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
  • 36,935 View
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  • 10 Web of Science
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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

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  • 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
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  • 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
Drug/Regimen
Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study
Jeong Mi Kim, Sang Soo Kim, Jong Ho Kim, Mi Kyung Kim, Tae Nyun Kim, Soon Hee Lee, Chang Won Lee, Ja Young Park, Eun Sook Kim, Kwang Jae Lee, Young Sik Choi, Duk Kyu Kim, In Joo Kim
Diabetes Metab J. 2020;44(1):67-77.   Published online July 11, 2019
DOI: https://doi.org/10.4093/dmj.2018.0274
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AbstractAbstract PDFPubReader   
Background

There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.

Methods

This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.

Results

Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).

Conclusion

Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Citations

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Clinical Diabetes & Therapeutics
Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Hae Kyung Yang, Seung-Hwan Lee, Juyoung Shin, Yoon-Hee Choi, Yu-Bae Ahn, Byung-Wan Lee, Eun Jung Rhee, Kyung Wan Min, Kun-Ho Yoon
Diabetes Metab J. 2019;43(3):287-301.   Published online December 20, 2018
DOI: https://doi.org/10.4093/dmj.2018.0054
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.

Methods

A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.

Results

The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups.

Conclusion

In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

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