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Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.

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Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

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  Diabetes & Metabolism Journal.2021; 45(4): 505.     CrossRef
• 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 & Metabolism Journal.2021; 45(6): 921.     CrossRef
• SGLT2i: beyond the glucose-lowering effect
  Lihua Ni, Cheng Yuan, Guopeng Chen, Changjiang Zhang, Xiaoyan Wu
  Cardiovascular Diabetology.2020;[Epub]     CrossRef
• Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial
  Eugene Han, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
  Journal of Clinical Medicine.2020; 9(1): 259.     CrossRef
• Stability Indicating, pH and pKa Dependent HPLC–DAD Method for the Simultaneous Determination of Weakly Ionizable Empagliflozin, Dapagliflozin and Canagliflozin in Pharmaceutical Formulations
  Shahzad Sharif, Rashida Bashir, Ahmad Adnan, Sabiha Mansoor, Izaz Ahmad, Ayoub Rashid Ch, Muhammad Saqlain Tahir
  Chromatographia.2020; 83(12): 1453.     CrossRef
• Cardiorenal protection with SGLT2: Lessons from the cardiovascular outcome trials
  José Silva‐Cardoso, Omar Sheikh, Mouhamed Nashawi, Son Pham, Kelly M. Gallegos, Laith R. Dinkha, Robert J. Chilton
  Journal of Diabetes.2020; 12(4): 279.     CrossRef
• Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes
  Jin Bong Choi, Je Mo Yoo, Ye-Jee Lee, Jae Woong Kim, Seung-Ju Lee, Hee Youn Kim, Dong Sup Lee, Seung-Hyun Ko, Hyun-Sop Choe
  International Neurourology Journal.2020; 24(1): 21.     CrossRef
• Sodium‐glucose cotransporter 2 inhibitors regulate ketone body metabolism via inter‐organ crosstalk
  Jin Hee Kim, Minyoung Lee, Soo Hyun Kim, So Ra Kim, Byung‐Wan Lee, Eun Seok Kang, Bong‐Soo Cha, Jin Won Cho, Yong‐ho Lee
  Diabetes, Obesity and Metabolism.2019; 21(4): 801.     CrossRef
• Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  Jae Hyun Bae, Eun-Gee Park, Sunhee Kim, Sin Gon Kim, Seokyung Hahn, Nam Hoon Kim
  Scientific Reports.2019;[Epub]     CrossRef
• SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart
  Chenguang Li, Jie Zhang, Mei Xue, Xiaoyu Li, Fei Han, Xiangyang Liu, Linxin Xu, Yunhong Lu, Ying Cheng, Ting Li, Xiaochen Yu, Bei Sun, Liming Chen
  Cardiovascular Diabetology.2019;[Epub]     CrossRef
• An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials
  Ernest Adeghate, Sahar Mohsin, Faisal Adi, Fares Ahmed, Ali Yahya, Huba Kalász, Kornelia Tekes, Ernest A. Adeghate
  Expert Opinion on Investigational Drugs.2019; 28(9): 811.     CrossRef
• Stability‐indicating chromatographic and chemometric methods for environmentally benign determination of canagliflozin and its major degradation product; A comparative study and greenness assessment
  Aml A. Emam, Nada S. Abdelwahab
  Biomedical Chromatography.2019;[Epub]     CrossRef
• A Lower Baseline Urinary Glucose Excretion Predicts a Better Response to the Sodium Glucose Cotransporter 2 Inhibitor
  You-Cheol Hwang, Jae Hyeon Kim, Byung-Wan Lee, Woo Je Lee
  Diabetes & Metabolism Journal.2019; 43(6): 898.     CrossRef
• 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 & Metabolism Journal.2019; 43(2): 158.     CrossRef
• Comparative Efficacy and Safety Among Sodium-glucose Cotransporter-2 Inhibitors in Type 2 Diabetes – Results from a Retrospective Single-centre Study
  Manash P Baruah, Sanjay Kalra
  European Endocrinology.2019; 15(2): 113.     CrossRef
• Canagliflozin stability study and ecofriendly chromatographic determination of its degradation product: A comparative study
  Aml A. Emam
  Journal of Separation Science.2018; 41(4): 822.     CrossRef
• Efficacy and tolerability of novel triple combination therapy in drug-naïve patients with type 2 diabetes from the TRIPLE-AXEL trial: protocol for an open-label randomised controlled trial
  Nam Hoon Kim, Soo Lim, Soo Heon Kwak, Min Kyong Moon, Jun Sung Moon, Yong-ho Lee, Ho Chan Cho, Juneyoung Lee, Sin Gon Kim
  BMJ Open.2018; 8(9): e022448.     CrossRef
• Short-term outcomes of patients with Type 2 diabetes mellitus treated with canagliflozin compared with sitagliptin in a real-world setting
  YL Shao, KH Yee, SK, Koh, YF Wong, LY Yeoh, S Low, CF Sum
  Singapore Medical Journal.2018; 59(5): 251.     CrossRef
• Clinical implications of current cardiovascular outcome trials with sodium glucose cotransporter-2 (SGLT2) inhibitors
  Soo Lim, Robert H. Eckel, Kwang Kon Koh
  Atherosclerosis.2018; 272: 33.     CrossRef
• Effect of Empagliflozin, a Selective Sodium-Glucose Cotransporter 2 Inhibitor, on Kidney and Peripheral Nerves in Streptozotocin-Induced Diabetic Rats
  Kyung Ae Lee, Heung Yong Jin, Na Young Lee, Yu Ji Kim, Tae Sun Park
  Diabetes & Metabolism Journal.2018; 42(4): 338.     CrossRef
• The effect of Ramadan fasting and continuing sodium-glucose co-transporter-2 (SGLT2) inhibitor use on ketonemia, blood pressure and renal function in Muslim patients with type 2 diabetes
  Yanli Shao, Gwyneth Joy Lim, Chin Lian Chua, Yip Fong Wong, Ester Chai Kheng Yeoh, Serena Kiat Mun Low, Chee Fang Sum
  Diabetes Research and Clinical Practice.2018; 142: 85.     CrossRef
• Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease
  Dug-Hyun Choi, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, Bo-Yeon Kim
  Endocrinology and Metabolism.2018; 33(3): 387.     CrossRef
• Comparison between sodium–glucose cotransporter 2 inhibitors and pioglitazone as additions to insulin therapy in type 2 diabetes patients: A systematic review with an indirect comparison meta‐analysis
  Yun Kyung Cho, Ye‐Jee Kim, Yu Mi Kang, Seung Eun Lee, Joong‐Yeol Park, Woo Je Lee, Chang Hee Jung
  Journal of Diabetes Investigation.2018; 9(4): 882.     CrossRef
• Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea
  Eugene Han, Ari Kim, Sung Jae Lee, Je-Yon Kim, Jae Hyeon Kim, Woo Je Lee, Byung-Wan Lee
  Diabetes Therapy.2018; 9(4): 1689.     CrossRef
• Combining SGLT2 Inhibition With a Thiazolidinedione Additively Attenuate the Very Early Phase of Diabetic Nephropathy Progression in Type 2 Diabetes Mellitus
  Eugene Han, Eugene Shin, Gyuri Kim, Ji-Yeon Lee, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
  Frontiers in Endocrinology.2018;[Epub]     CrossRef
• Clinical parameters affecting dapagliflozin response in patients with type 2 diabetes
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  Diabetes & Metabolism.2017; 43(2): 191.     CrossRef
• Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and immunomodulatory compounds
  Daniella B.R. Insuela, Vinicius F. Carvalho
  European Journal of Pharmacology.2017; 812: 64.     CrossRef
• Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J‐STEP/INS): Results of a 16‐week randomized, double‐blind, placebo‐controlled multicentre trial
  Yasuo Terauchi, Masahiro Tamura, Masayuki Senda, Ryoji Gunji, Kohei Kaku
  Diabetes, Obesity and Metabolism.2017; 19(10): 1397.     CrossRef
• A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes
  Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Tae-Seok Lim, Ki-Ho Song, Ki-Dong Yoo, Yu-Bae Ahn, Seung-Hyun Ko
  Lipids in Health and Disease.2017;[Epub]     CrossRef
• Morning Spot Urine Glucose-to-Creatinine Ratios Predict Overnight Urinary Glucose Excretion in Patients With Type 2 Diabetes
  So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Sun Hee Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Jeong-Ho Kim, Byung-Wan Lee
  Annals of Laboratory Medicine.2017; 37(1): 9.     CrossRef
• The Relationship between Increases in Morning Spot Urinary Glucose Excretion and Decreases in HbA1C in Patients with Type 2 Diabetes After Taking an SGLT2 Inhibitor: A Retrospective, Longitudinal Study
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  Diabetes Therapy.2017; 8(3): 601.     CrossRef
• Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria
  Siqian Gong, Jiandong Guo, Xueyao Han, Meng Li, Lingli Zhou, Xiaoling Cai, Yu Zhu, Yingying Luo, Simin Zhang, Xianghai Zhou, Yumin Ma, Linong Ji
  The Journal of Clinical Endocrinology & Metabolism.2017; 102(5): 1548.     CrossRef
• Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes
  Seok Joon Shin, Sungjin Chung, Soo Jung Kim, Eun-Mi Lee, Young-Hye Yoo, Ji-Won Kim, Yu-Bae Ahn, Eun-Sook Kim, Sung-Dae Moon, Myung-Jun Kim, Seung-Hyun Ko, Kwang-Hyun Baek
  PLOS ONE.2016; 11(11): e0165703.     CrossRef
• Sodium–glucose cotransporter 2 inhibitors: an evidence-based practice approach to their use in the natural history of type 2 diabetes
  Stanley S. Schwartz, Intekhab Ahmed
  Current Medical Research and Opinion.2016; 32(5): 907.     CrossRef
• Insulin resistance, role of metformin and other non-insulin therapies in pediatric type 1 diabetes
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  Pediatric Diabetes.2016; 17(8): 545.     CrossRef
• Renal threshold for glucose reabsorption predicts diabetes improvement by sodium‐glucose cotransporter 2 inhibitor therapy
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• Sodium-glucose co-transporter inhibition in the treatment of diabetes: Sweetening the pot
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• A simple and sensitive high performance liquid chromatography assay with a fluorescence detector for determination of canagliflozin in human plasma
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  Analytical Methods.2015; 7(7): 3028.     CrossRef
• Efficacy and safety of sodium–glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years
  Xiang-Yang Liu, Ning Zhang, Rui Chen, Jia-Guo Zhao, Pei Yu
  Journal of Diabetes and its Complications.2015; 29(8): 1295.     CrossRef
• Severe hypercalcemia and hypernatremia in a patient treated with canagliflozin
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