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Original Articles
- Drug/Regimen
- Pioglitazone as Add-on THERAPY in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial
- Ji Hye Heo, Kyung Ah Han, Jun Hwa Hong, Hyun-Ae Seo, Eun-Gyoung Hong, Jae Myung Yu, Hye Seung Jung, Bong-Soo Cha
- Received September 1, 2023 Accepted October 25, 2023 Published online February 2, 2024
- DOI: https://doi.org/10.4093/dmj.2023.0314 [Epub ahead of print]
- 1,198 View
- 114 Download
-
Abstract
PDF
Supplementary Material
PubReader 
ePub - Background
This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135).
Results
At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (–0.47%; 95% confidence interval, –0.61 to –0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%).
Conclusion
Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.
- Complications
- Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus
- Hae Kyung Kim, Minyoung Lee, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
- Diabetes Metab J. 2022;46(1):104-116. Published online July 13, 2021
- DOI: https://doi.org/10.4093/dmj.2020.0273
- 5,670 View
- 191 Download
- 4 Web of Science
- 5 Crossref
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Graphical Abstract
Abstract
PDFSupplementary MaterialPubReader ePub - Background
Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM.
Methods
A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured.
Results
Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01).
Conclusion
The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future. -
Citations
Citations to this article as recorded by
- Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial
Xiao Tong Teong, Kai Liu, Andrew D. Vincent, Julien Bensalem, Bo Liu, Kathryn J. Hattersley, Lijun Zhao, Christine Feinle-Bisset, Timothy J. Sargeant, Gary A. Wittert, Amy T. Hutchison, Leonie K. Heilbronn
Nature Medicine.2023; 29(4): 963. CrossRef - Significance of Diabetic Kidney Disease Biomarkers in Predicting Metabolic-Associated Fatty Liver Disease
Jaehyun Bae, Byung-Wan Lee
Biomedicines.2023; 11(7): 1928. CrossRef - Abdominal adipose tissue and type 2 diabetic kidney disease: adipose radiology assessment, impact, and mechanisms
Fei Lu, Jinlei Fan, Fangxuan Li, Lijing Liu, Zhiyu Chen, Ziyu Tian, Liping Zuo, Dexin Yu
Abdominal Radiology.2023; 49(2): 560. CrossRef - β‐Amyrin ameliorates diabetic nephropathy in mice and regulates the miR‐181b‐5p/HMGB2 axis in high glucose‐stimulated HK‐2 cells
Wenhua Xu, Hongwu Zhang, Qinfeng Zhang, Jialan Xu
Environmental Toxicology.2022; 37(3): 637. CrossRef - High Glycated Hemoglobin Instead of High Body Mass Index Might Increase the Urine N-Acetyl-β-D-glucosaminidase Con-Centration in Children and Adolescents with Diabetes Mellitus
Jin-Soon Suh, Kyoung Soon Cho, Seul Ki Kim, Shin-Hee Kim, Won Kyoung Cho, Min Ho Jung, Moon Bae Ahn
Life.2022; 12(6): 879. CrossRef
- Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial
Review
- Drug/Regimen
- Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
- Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
- Diabetes Metab J. 2021;45(3):326-336. Published online April 19, 2021
- DOI: https://doi.org/10.4093/dmj.2020.0272
- 9,777 View
- 405 Download
- 22 Web of Science
- 23 Crossref
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Graphical Abstract
Abstract
PDFSupplementary MaterialPubReader ePub
- Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.
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Citations
Citations to this article as recorded by- Etiology of Drug-Induced Edema: A Review of Dihydropyridine, Thiazolidinedione, and Other Medications Causing Edema
Evan S Sinnathamby, Bretton T Urban, Robert A Clark, Logan T Roberts, Audrey J De Witt, Danielle M Wenger, Aya Mouhaffel, Olga Willett, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D Kaye, Giustino Varrassi
Cureus.2024;[Epub] CrossRef - Novel thiazolidin-4-one benzenesulfonamide hybrids as PPARγ agonists: Design, synthesis and in vivo anti-diabetic evaluation
Islam H. Ali, Rasha M. Hassan, Ahmed M. El Kerdawy, Mahmoud T. Abo-Elfadl, Heba M.I. Abdallah, Francesca Sciandra, Iman A.Y. Ghannam
European Journal of Medicinal Chemistry.2024; 269: 116279. CrossRef - The role of the methoxy group in approved drugs
Debora Chiodi, Yoshihiro Ishihara
European Journal of Medicinal Chemistry.2024; : 116364. CrossRef - Thiazolidinedione an Auspicious Scaffold as PPAR-γ Agonist: its Possible Mechanism to Manoeuvre against Insulin Resistant Diabetes Mellitus.
Sourav Basak, Anjali Murmu, Balaji Wamanrao Matore, Partha Pratim Roy, Jagadish Singh
European Journal of Medicinal Chemistry Reports.2024; : 100160. CrossRef - Efficacy and Safety of Novel Thiazolidinedione Rivoglitazone in Type-2 Diabetes a Meta-Analysis
Deep Dutta, Jyoti Kadian, Indira Maisnam, Ashok Kumar, Saptarshi Bhattacharya, Meha Sharma
Indian Journal of Endocrinology and Metabolism.2023; 27(4): 286. CrossRef - Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef - Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef - Synthesis, Characterization, and Pharmacokinetic Studies of Thiazolidine-2,4-Dione Derivatives
Bushra Ansari, Haroon Khan, Muhammad Saeed Jan, Khalaf F. Alsharif, Khalid J. Alzahrani, Umer Rashid, Abdul Saboor Pirzada, Vinod Kumar Tiwari
Journal of Chemistry.2023; 2023: 1. CrossRef - Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef - Evaluation of pharmacokinetic interactions between lobeglitazone, empagliflozin, and metformin in healthy subjects
Heeyoung Kim, Choon Ok Kim, Hyeonsoo Park, Min Soo Park, Dasohm Kim, Taegon Hong, Yesong Shin, Byung Hak Jin
Translational and Clinical Pharmacology.2023; 31(1): 59. CrossRef - Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
Cardiovascular Diabetology.2023;[Epub] CrossRef - Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model
Yun Kyung Lee, Tae Jung Oh, Ji In Lee, Bo Yoon Choi, Hyen Chung Cho, Hak Chul Jang, Sung Hee Choi
European Journal of Pharmacology.2023; 957: 175946. CrossRef - Thiazolidinediones: Recent Development in Analytical Methodologies
Tarang Patel, Vatsal Patel
Journal of Chromatographic Science.2023;[Epub] CrossRef - Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease
Shotaro Kamata, Akihiro Honda, Isao Ishii
Biomolecules.2023; 13(8): 1264. CrossRef - Lobeglitazone inhibits LPS-induced NLRP3 inflammasome activation and inflammation in the liver
Hye-Young Seo, So-Hee Lee, Ji Yeon Park, Eugene Han, Sol Han, Jae Seok Hwang, Mi Kyung Kim, Byoung Kuk Jang, Kenji Fujiwara
PLOS ONE.2023; 18(8): e0290532. CrossRef - Insulin sensitizers in 2023: lessons learned and new avenues for investigation
Jerry R. Colca, Steven P. Tanis, Rolf F. Kletzien, Brian N. Finck
Expert Opinion on Investigational Drugs.2023; 32(9): 803. CrossRef - Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach
Priyamvada Amol Arte, Kanchanlata Tungare, Mustansir Bhori, Renitta Jobby, Jyotirmoi Aich
Human Cell.2023; 37(1): 54. CrossRef - Lobeglitazone and Its Therapeutic Benefits: A Review
Balamurugan M, Sarumathy S, Robinson R
Cureus.2023;[Epub] 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 - Effect of the addition of thiazolidinedione to sodium-glucose cotransporter 2 inhibitor therapy on lipid levels in type 2 diabetes mellitus: a retrospective study using Korean National Health Insurance Service data
Taegyun Park, Kyungdo Han, Dongwook Shin, Jongho Park
Cardiovascular Prevention and Pharmacotherapy.2022; 4(3): 114. CrossRef - Design of Improved Antidiabetic Drugs: A Journey from Single to Multitarget Agents
Vassiliki‐Panagiota Tassopoulou, Ariadni Tzara, Angeliki P. Kourounakis
ChemMedChem.2022;[Epub] CrossRef - A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Y
Diabetes & Metabolism Journal.2022; 46(6): 855. CrossRef - Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages
Dabin Jeong, Wan-Kyu Ko, Seong-Jun Kim, Gong-Ho Han, Daye Lee, Seung-Hun Sheen, Seil Sohn
Biomedicines.2021; 9(10): 1432. CrossRef
- Etiology of Drug-Induced Edema: A Review of Dihydropyridine, Thiazolidinedione, and Other Medications Causing Edema
Original Article
- Basic Research
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- Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
- Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
- Diabetes Metab J. 2021;45(6):921-932. Published online February 22, 2021
- DOI: https://doi.org/10.4093/dmj.2020.0187
- 8,463 View
- 410 Download
- 20 Web of Science
- 21 Crossref
-
Graphical Abstract
Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity. -
Citations
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Nasser Safaie, Shahab Masoumi, Shaban Alizadeh, Pourya Mirzajanzadeh, Hamid Reza Nejabati, Mobasher Hajiabbasi, Vahid Alivirdiloo, Neda Chobdari Basmenji, Aysan Derakhshi Radvar, Ziba Majidi, Yousef Faridvand
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Clinics in Liver Disease.2023; 27(2): 397. CrossRef - SGLT2 Inhibitors and Kidney Diseases: A Clinical Perspective
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Current Medicinal Chemistry.2023; 30(23): 2595. CrossRef - Treatment of obesity-related diabetes: significance of thermogenic adipose tissue and targetable receptors
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Frontiers in Pharmacology.2023;[Epub] CrossRef - Immunomodulatory Effects of SGLT2 Inhibitors—Targeting Inflammation and Oxidative Stress in Aging
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Physiological Reports.2023;[Epub] CrossRef - Resting energy expenditure based on equation estimation can predict renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease
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Renal Failure.2023;[Epub] CrossRef - Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial
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Review
- Guideline/Fact Sheet
- Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
- Byung-Wan Lee, Yong-ho Lee, Cheol-Young Park, Eun-Jung Rhee, Won-Young Lee, Nan-Hee Kim, Kyung Mook Choi, Keun-Gyu Park, Yeon-Kyung Choi, Bong-Soo Cha, Dae Ho Lee, Korean Diabetes Association (KDA) Fatty Liver Research Group
- Diabetes Metab J. 2020;44(3):382-401. Published online May 11, 2020
- DOI: https://doi.org/10.4093/dmj.2020.0010
- 12,337 View
- 337 Download
- 42 Web of Science
- 42 Crossref
-
Abstract
PDFPubReader
This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.
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European Journal of Pharmacology.2023; 957: 175946. CrossRef - Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis
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Corrigendum
- Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
- Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
- Diabetes Metab J. 2019;43(5):731-731. Published online October 24, 2019
- DOI: https://doi.org/10.4093/dmj.2019.0188
- Corrects: Diabetes Metab J 2019;43(1):31
- 3,330 View
- 37 Download
Review
- Clinical Diabetes & Therapeutics
- Nonalcoholic Fatty Liver Disease and Diabetes: Part II: Treatment
- Kyung-Soo Kim, Byung-Wan Lee, Yong Jin Kim, Dae Ho Lee, Bong-Soo Cha, Cheol-Young Park
- Diabetes Metab J. 2019;43(2):127-143. Published online April 15, 2019
- DOI: https://doi.org/10.4093/dmj.2019.0034
- 7,667 View
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- 25 Web of Science
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Abstract
PDFPubReader
Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders that are often comorbid conditions. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. Although many drugs have been investigated, pioglitazone could be a first-line therapy in patients with NAFLD and diabetes. Many more drugs are currently being developed and investigated, and it is likely that combination strategies will be used for future treatment of NAFLD and diabetes. Attention should be paid to the management of NAFLD and diabetes and efforts should be made to intervene early and individualize treatment of NAFLD in patients with diabetes.
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Original Articles
- Metabolic Risk/Epidemiology
- Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus
- Hokyou Lee, Gyuri Kim, Young Ju Choi, Byung Wook Huh, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Eun Jig Lee, Yong-ho Lee, Kap Bum Huh
- Diabetes Metab J. 2020;44(2):267-276. Published online February 28, 2019
- DOI: https://doi.org/10.4093/dmj.2019.0001
- 6,870 View
- 150 Download
- 25 Web of Science
- 27 Crossref
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Abstract
PDFPubReader
Background Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.
Methods We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.
Results LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%,
P =0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively;P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34;P =0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51;P =0.002).Conclusions Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.
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- Anti-hepatopathy and anti-nephropathy activities of Taraxacum officinale in a rat model of Streptozotocin diabetes-induced hepatorenal toxicity and dyslipidemia via attenuation of oxidative stress, inflammation, apoptosis, electrolyte imbalances, and mito
- Clinical Diabetes & Therapeutics
- Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors
- Ji-Yeon Lee, Yongin Cho, Minyoung Lee, You Jin Kim, Yong-ho Lee, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
- Diabetes Metab J. 2019;43(2):158-173. Published online January 25, 2019
- DOI: https://doi.org/10.4093/dmj.2018.0057
- 5,935 View
- 160 Download
- 15 Web of Science
- 15 Crossref
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Abstract
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Background We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM).
Methods A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications.
Results After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome.
Conclusion A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.
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Citations
Citations to this article as recorded by- Predictors of efficacy of Sodium‐GLucose Transporter‐2 inhibitors and Glucagon‐Like Peptide 1 receptor agonists: A retrospective cohort study
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M. L. Morieri, I. Raz, A. Consoli, M. Rigato, A. Lapolla, F. Broglio, E. Bonora, A. Avogaro, G. P. Fadini, Federica Ginestra, Gloria Formoso, Agostino Consoli, Francesco Andreozzi, Giorgio Sesti, Salvatore Turco, Luigi Lucibelli, Adriano Gatti, Raffaella
Journal of Endocrinological Investigation.2023; 46(7): 1429. CrossRef - Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review
Katherine G. Young, Eram Haider McInnes, Robert J. Massey, Anna R. Kahkoska, Scott J. Pilla, Sridharan Raghavan, Maggie A. Stanislawski, Deirdre K. Tobias, Andrew P. McGovern, Adem Y. Dawed, Angus G. Jones, Ewan R. Pearson, John M. Dennis, Deirdre K. Tobi
Communications Medicine.2023;[Epub] CrossRef - Predictors of HbA1c treatment response to add-on medication following metformin monotherapy: a population-based cohort study
Wei Ying Tan, Wynne Hsu, Mong Li Lee, Ngiap Chuan Tan
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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
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Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
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Kyung-Soo Kim
Diabetes & Metabolism Journal.2019; 43(3): 377. CrossRef - Response: Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors (Diabetes Metab J 2019;43:158–73)
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Review
- Complications
- Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis
- Yong-ho Lee, Yongin Cho, Byung-Wan Lee, Cheol-Young Park, Dae Ho Lee, Bong-Soo Cha, Eun-Jung Rhee
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- DOI: https://doi.org/10.4093/dmj.2019.0011
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- 8,200 View
- 167 Download
- 106 Web of Science
- 101 Crossref
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Abstract
PDFPubReader
Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders whose prevalence rates are expected to rise worldwide, corresponding to aging and increasingly obese populations. Compared to the general population (around 25%), 50% to 70% of people with diabetes have NAFLD, and NAFLD severity (including fibrosis) tends to be worsened by the presence of diabetes. NAFLD is considered an emerging risk factor for type 2 diabetes mellitus and a contributor to the development of chronic diabetes-related complications. This reciprocal relationship demonstrates the importance of confirming suspected NAFLD in patients with diabetes. Due to the invasive nature of liver biopsy to assess NAFLD status, various alternative non-invasive modalities have been developed and validated. Here, we summarized the epidemiology of NAFLD in patients with diabetes and reviewed currently available imaging modalities and biomarker-based prediction models for their ability to detect liver steatosis and/or fibrosis.
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Original Article
- Others
- Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial
- Kyung-Wan Min, Bon Jeong Ku, Ji-Hyun Lee, Min-Seon Kim, Kyu-Jeung Ahn, Moon-Kyu Lee, Satoshi Kokubo, Satoshi Yoshida, Hyun-Ji Cho, Bong-Soo Cha
- Diabetes Metab J. 2017;41(2):135-145. Published online January 11, 2017
- DOI: https://doi.org/10.4093/dmj.2017.41.2.135
- 4,941 View
- 59 Download
- 13 Web of Science
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Abstract
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Background This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.
Methods This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea.
Results Eighty-two Korean patients received ipragliflozin (
n =43) or placebo (n =39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P <0.001). Compared to placebo, FPG and body weight also decreased significantly (bothP <0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection.Conclusion Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.
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Citations
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Derun Taner Ertugrul, Erdal Kan, Cigdem Bahadir Tura, Haci Bayram Tugtekin, Hayati Ayakta, Mehmet Celebioglu, Ceren Yılmaz, Onur Utebay, Ilhan Yetkin, Eren Gurkan, Kerem Sezer, Ramazan Gen, Suleyman Ozcaylak, Yildiz Okuturlar, Mehmet Coskun, Nilgun Govec
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