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      A Lower Baseline Urinary Glucose Excretion Predicts a Better Response to the Sodium Glucose Cotransporter 2 Inhibitor

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          Abstract

          We aimed to identify the clinical variables associated with a better glucose-lowering response to the sodium glucose cotransporter 2 inhibitor ipragliflozin in people with type 2 diabetes mellitus (T2DM). We especially focused on urinary glucose excretion (UGE). This was a single-arm multicenter prospective study. A total of 92 people with T2DM aged 20 to 70 years with glycosylated hemoglobin (HbA1c) levels ≥7.0% and ≤9.5% were enrolled. Ipragliflozin (50 mg) was added to the background therapy for these people for 12 weeks. After 3 months treatment with ipragliflozin, the mean HbA1c levels were decreased from 7.6% to 6.9% and 62.0% of the people reached the HbA1c target of less than 7.0% ( P<0.001). In addition, body weight, blood pressure, and lipid parameters were improved after ipragliflozin treatment (all P<0.001). The baseline HbA1c ( r=0.66, P<0.001) and morning spot urine glucose to creatinine ratio ( r=−0.30, P=0.001) were independently associated with the HbA1c reduction. Ipragliflozin treatment for 12 weeks improves glycemic control and other metabolic parameters. A higher HbA1c and lower UGE at baseline predicts a better glucose-lowering efficacy of ipragliflozin.

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          Glucose handling by the kidney.

          The kidney contributes to glucose homeostasis through processes of gluconeogenesis, glucose filtration, glucose reabsorption, and glucose consumption. Each of these processes can be altered in patients with type-2 diabetes (T2DM), providing potential targets for novel therapies. Recent studies have indicated that the kidney is responsible for up to 20% of all glucose production via gluconeogenesis. In patients with T2DM, overall glucose production increases by as much as 300%, with equal contributions from hepatic and renal sources. This increased production contributes not only to increased fasting glucose in T2DM patients but also to raised postprandial glucose because, in contrast to the liver, glucose ingestion increases renal gluconeogenesis. Under normal circumstances, up to 180 g/day of glucose is filtered by the renal glomerulus and virtually all of it is subsequently reabsorbed in the proximal convoluted tubule. This reabsorption is effected by two sodium-dependent glucose cotransporter (SGLT) proteins. SGLT2, situated in the S1 segment, is a low-affinity high-capacity transporter reabsorbing up to 90% of filtered glucose. SGLT1, situated in the S3 segment, is a high-affinity low-capacity transporter reabsorbing the remaining 10%. In patients with T2DM, renal reabsorptive capacity maladaptively increases from a normal level of 19.5 to 23.3 mmol/l/min. Once glucose has been reabsorbed into the tubular epithelial cells, it diffuses into the interstitium across specific facilitative glucose transporters (GLUTs). GLUT1 and GLUT2 are associated with SGLT1 and SGLT2, respectively.
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            A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor

            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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              Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 Inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus

              To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin (TS-071) in Japanese patients with type 2 diabetes mellitus (T2DM).
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                Author and article information

                Journal
                Diabetes Metab J
                Diabetes Metab J
                DMJ
                Diabetes & Metabolism Journal
                Korean Diabetes Association
                2233-6079
                2233-6087
                December 2019
                14 June 2019
                : 43
                : 6
                : 898-905
                Affiliations
                [1 ]Department of Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.
                [2 ]Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
                [3 ]Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                [4 ]Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Woo Je Lee. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. lwjatlas@ 123456amc.seoul.kr
                Corresponding author: Byung-Wan Lee. Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. bwanlee@ 123456yuhs.ac
                Author information
                https://orcid.org/0000-0003-4033-7874
                https://orcid.org/0000-0002-9899-4992
                https://orcid.org/0000-0002-9605-9693
                Article
                10.4093/dmj.2018.0257
                6943269
                31237132
                146ab735-5e06-4de9-a778-428dc4965406
                Copyright © 2019 Korean Diabetes Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 December 2018
                : 13 February 2019
                Categories
                Short Communication
                Clinical Diabetes & Therapeutics

                Endocrinology & Diabetes
                diabetes mellitus, type 2,glycosuria,ipragliflozin,sodium-glucose transporter 2

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