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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, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators
Diabetes Metab J. 2024;48(5):915-928.   Published online April 23, 2024
DOI: https://doi.org/10.4093/dmj.2023.0259
  • 2,865 View
  • 271 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.
Drug/Regimen
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Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study
Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
Diabetes Metab J. 2021;45(3):339-348.   Published online May 28, 2020
DOI: https://doi.org/10.4093/dmj.2019.0203
  • 9,452 View
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  • 14 Web of Science
  • 17 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.

Methods

In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).

Results

At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P<0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%, P<0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL, P<0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.

Conclusion

Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.

Citations

Citations to this article as recorded by  
  • Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
    Yuanyuan Luo, Ruojing Bai, Wei Zhang, Guijun Qin
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Continuous Glucose Monitoring Profiles and Health Outcomes After Dapagliflozin Plus Saxagliptin vs Insulin Glargine
    Donald C Simonson, Marcia A Testa, Ella Ekholm, Maxwell Su, Tina Vilsbøll, Serge A Jabbour, Marcus Lind
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(12): e2261.     CrossRef
  • Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR‐Pooled analysis
    Khawaja M. Talha, Jennifer Green, Gerasimos Filippatos, Stuart Pocock, Faiez Zannad, Martina Brueckmann, Elke Schueler, Anne Pernille Ofstad, João Pedro Ferreira, Stefan D. Anker, Javed Butler, Julio Rosenstock, Milton Packer
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  • Dapagliflozin in heart failure and type 2 diabetes: Efficacy, cardiac and renal effects, safety
    Pei-Ling Yu, You Yu, Shuang Li, Bai-Chen Mu, Ming-Hua Nan, Min Pang
    World Journal of Diabetes.2024; 15(7): 1518.     CrossRef
  • Glycemic Variability in Pancreatogenic Diabetes Mellitus: characteristics, Risks, Potential Mechanisms, and Treatment Possibilities
    Yuyan Sun, Bing Lu, Yuanwen Hu, Yingqi Lv, Shao Zhong
    International Journal of General Medicine.2024; Volume 17: 4297.     CrossRef
  • Risk of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Treated with Dapagliflozin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
    Zhigui Zheng, Dongyuan He, Jianguo Chen, Xiaohui Xie, Yunan Lu, Binbin Wu, Xinxin Jiang
    Clinical Drug Investigation.2023; 43(4): 209.     CrossRef
  • Effect of SGLT2 Inhibitors and Metformin on Inflammatory and Prognostic Biomarkers in Type 2 Diabetes Patients
    Yang Cao, Ning Liang, Ting Liu, Jingai Fang, Xiaodong Zhang
    Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(4): 530.     CrossRef
  • What is Glycaemic Variability and which Pharmacological Treatment Options are Effective? A Narrative Review
    Juan Miguel Huertas Cañas, Maria Alejandra Gomez Gutierrez, Andres Bedoya Ossa
    European Endocrinology.2023; 19(2): 4.     CrossRef
  • La variabilité glycémique : un facteur de risque singulier à conjuguer au pluriel
    Louis Monnier, Claude Colette, Fabrice Bonnet, David Owens
    Médecine des Maladies Métaboliques.2022; 16(1): 15.     CrossRef
  • Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
    Min Jeong Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2022; 46(1): 49.     CrossRef
  • Effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on serum urate levels in patients with and without diabetes: a systematic review and meta-regression of 43 randomized controlled trials
    Alicia Swee Yan Yip, Shariel Leong, Yao Hao Teo, Yao Neng Teo, Nicholas L. X. Syn, Ray Meng See, Caitlin Fern Wee, Elliot Yeung Chong, Chi-Hang Lee, Mark Y. Chan, Tiong-Cheng Yeo, Raymond C. C. Wong, Ping Chai, Ching-Hui Sia
    Therapeutic Advances in Chronic Disease.2022;[Epub]     CrossRef
  • Hypoglycemic agents and glycemic variability in individuals with type 2 diabetes: A systematic review and network meta-analysis
    SuA Oh, Sujata Purja, Hocheol Shin, Minji Kim, Eunyoung Kim
    Diabetes and Vascular Disease Research.2022;[Epub]     CrossRef
  • The Clinical Effect of Dapagliflozin in Patients with Angiographically Confirmed Coronary Artery Disease and Concomitant Type 2 Diabetes Mellitus
    Yana Yu. Dzhun, Yevhen Yu. Marushko, Yanina A. Saienko, Nadiya M. Rudenko, Borys M. Mankovsky
    Ukrainian Journal of Cardiovascular Surgery.2022; 30(3): 35.     CrossRef
  • Stress-Induced Hyperglycaemia in Non-Diabetic Patients with Acute Coronary Syndrome: From Molecular Mechanisms to New Therapeutic Perspectives
    Alessandro Bellis, Ciro Mauro, Emanuele Barbato, Antonio Ceriello, Antonio Cittadini, Carmine Morisco
    International Journal of Molecular Sciences.2021; 22(2): 775.     CrossRef
  • Glycemic Variability Impacted by SGLT2 Inhibitors and GLP 1 Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis
    Heeyoung Lee, Se-eun Park, Eun-Young Kim
    Journal of Clinical Medicine.2021; 10(18): 4078.     CrossRef
  • Effect of Dapagliflozin on Glycemic Variability in Patients with Type 2 Diabetes under Insulin Glargine Combined with Other Oral Hypoglycemic Drugs
    Menghui Luo, Xiaocen Kong, Huiying Wang, Xiaofang Zhai, Tingting Cai, Bo Ding, Yun Hu, Ting Jing, Xiaofei Su, Huiqin Li, Jianhua Ma, Yoshifumi Saisho
    Journal of Diabetes Research.2020; 2020: 1.     CrossRef
  • Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control
    Jee Hee Yoo, Jae Hyeon Kim
    Diabetes & Metabolism Journal.2020; 44(6): 828.     CrossRef
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
  • 7,184 View
  • 122 Download
  • 15 Web of Science
  • 15 Crossref
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.

Citations

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    Ali Mohammadian, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Niloufar Rasaei, Hossein Bahari, Samira Rastgoo, Reza Bagheri, Farideh Shiraseb, Omid Asbaghi
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Statin Discontinuation after Achieving a Target Low Density Lipoprotein Cholesterol Level in Type 2 Diabetic Patients without Cardiovascular Disease: A Randomized Controlled Study
Seung-Hwan Lee, Hyuk-Sang Kwon, Yong-Moon Park, Seung-Hyun Ko, Yoon-Hee Choi, Kun-Ho Yoon, Yu-Bae Ahn
Diabetes Metab J. 2014;38(1):64-73.   Published online February 19, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.1.64
  • 4,753 View
  • 53 Download
  • 17 Web of Science
  • 16 Crossref
AbstractAbstract PDFPubReader   
Background

This study investigated the rate of relapse of dyslipidemia and the factors which could predict relapse following a short-term statin discontinuation after achieving a target low density lipoprotein cholesterol (LDL-C) level in type 2 diabetic patients without cardiovascular disease (CVD).

Methods

Ninety-nine subjects on rosuvastatin treatment and whose LDL-C level was lower than 100 mg/dL were randomly assigned to discontinue or maintain statin treatment at a 2:1 ratio. The subjects were followed-up after 10 weeks. A relapse of dyslipidemia was defined as a reascent of LDL-C level to greater than 100 mg/dL.

Results

The statin discontinuation group had a significant rate of relapse compared to the maintenance group (79% vs. 3%, respectively). Pretreatment and baseline lipid levels, their ratios, and hemoglobin A1c level were significantly different between the relapse and nonrelapse groups. The pretreatment and baseline lipid profiles and their ratios were independently associated with relapse. The pretreatment LDL-C level was the most useful parameter for predicting a relapse, with a cutoff of 123 mg/dL. During the follow-up period, no CVD event was noted.

Conclusion

The relapse rate of dyslipidemia was high when statins were discontinued in type 2 diabetic patients without CVD. Statin discontinuation should be considered carefully based on the pretreatment lipid profiles of patients.

Citations

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Review
Ubiquitous Diabetes Management System via Interactive Communication Based on Information Technologies: Clinical Effects and Perspectives
Jae-Hyoung Cho, Hun-Sung Kim, Jae-Hoon Han, Jin-Hee Lee, Jeong-Ah Oh, Yoon-Hee Choi, Kun-Ho Yoon
Korean Diabetes J. 2010;34(5):267-273.   Published online October 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.5.267
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  • 30 Download
  • 16 Crossref
AbstractAbstract PDFPubReader   

New diabetes management systems based on interactive communication have been introduced recently, accompanying rapid advances in information technology; these systems are referred to as "ubiquitous diabetes management systems." In such ubiquitous systems, patients and medical teams can communicate via Internet or telecommunications, with patients uploading their glucose data and personal information, and medical teams sending optimal feedback. Clinical evidence from both long-term and short-term trials has been reported by some researchers. Such systems appear to be effective not only in reducing the levels of HbA1c but also in stabilizing glucose control. However, most notably, evidence for the cost-effectiveness of such a system should be demonstrated before it can be propagated out to the general population in actual clinical practice. To establish a cost-effective model, various types of clinical decision supporting software designed to reduce the labor time of physicians must first be developed. A number of sensors and devices for monitoring patients' data are expected to be available in the near future; thus, methods for automatic interconnections between devices and web charts were also developed. Further investigations to demonstrate the clinical outcomes of such a system should be conducted, hopefully leading to a new paradigm of diabetes management.

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Diabetes Metab J : Diabetes & Metabolism Journal
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