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Diabetes sglt2

Kim A Connelly, Deepak L Bhatt, Subodh Verma
Heart failure and renal disease remain significant complications in people with type 2 diabetes (T2D). Recent outcome studies with sodium-glucose cotransporter-2 (SGLT2) inhibitors have provided increasing insights, with the latest reporting trial DECLARE-TIMI 58 (Wiviott et al., 2018), pointing toward a role for these agents in the primary prevention of cardio-renal complications in T2D.
December 4, 2018: Cell Metabolism
Mojca Lunder, Miodrag Janić, Miha Japelj, Andrej Juretič, Andrej Janež, Mišo Šabovič
BACKGROUND: Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin's effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients. METHODS: Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively)...
December 3, 2018: Cardiovascular Diabetology
Jingbo Hu, Yongzhong Du
During the years, while treatment strategy for diabetes mellitus has improved, the incidence of diabetes worldwide increases continuously. Chronic kidney disease (CKD) is one of the major diabetic microvascular complications, and a primary cause leading to end-stage renal disease (ESRD). The progression to ESRD, affected by hyperglycemia and hypertension, is characterized by microalbuminuria and macroalbuminuria. With advances in understanding the pathogenesis of CKD in diabetic patients, many novel therapeutic targets have been proposed, and the corresponding agents are being developed continually to prevent the progression of CKD...
December 3, 2018: Expert Review of Clinical Pharmacology
Masayuki Kaneko, Mamoru Narukawa
BACKGROUND AND OBJECTIVE: Empagliflozin and canagliflozin decreased the risk of major adverse cardiovascular events (MACE) compared with placebo in randomized clinical trials which were conducted to evaluate their cardiovascular risks. However, canagliflozin increased the risks of amputation and bone fracture, and the reasons for these observed differences remain unclear. The objective of this study was to evaluate the safety risks, specifically the risks of amputation and bone fracture, associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors by using the difference in restricted mean survival time (RMST), an alternative measure to the hazard ratio...
November 30, 2018: Clinical Drug Investigation
Pedro Pujante, Jessica Ares, Carmen Maciá, Raúl Rodriguez Escobedo, Edelmiro Menéndez, Elías Delgado
OBJECTIVE: To analyze the effect of sodium glucose cotransporter 2 (SGLT2) inhibitors in a group of insulin-dependent type 2 diabetes mellitus (T2D) patients. PATIENTS AND METHODS: One hundred and five insulin treated T2D patients were enrolled. Primary endpoints were: fasting plasma glucose, HbA1c, weight, total insulin doses (TDI), total basal insulin (TDB) and total rapid insulin (TDR). Secondary variables were: total cholesterol, LDL cholesterol (cLDL), HDL cholesterol (cHDL), triglycerides and systolic (SBP) and diastolic (DBP) blood pressure...
November 29, 2018: Medicina Clínica
Hong Ding, Kevin Ye, Chris R Triggle
Diabetes is associated with a high risk of cardiovascular complications and ideally anti-diabetic drugs should not only reduce metabolic abnormalities but also reduce the negative impact of diabetes on vascular function; however, lowering blood glucose levels does not necessarily reduce cardiovascular events. Endothelial dysfunction, defined as a reduction in endothelium-dependent vasodilation, is the earliest indicator of vascular disease and this raises the question: Do the currently used anti-diabetic drugs protect endothelial function? Metformin, in use for 60 years, is the first choice drug for type 2 diabetes and based on pre-clinical and clinical data metformin has proven cardiovascular protective actions; in contrast SGLT2 inhibitors were only introduced in 2013 but show great promise...
November 28, 2018: Current Opinion in Pharmacology
Shoji Takakura, Toshiyuki Takasu
The first dose of a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor induces osmotic diuresis, and can thereby affect cardiovascular activity in hyperglycemic patients. We aimed to determine whether the first dose of the selective SGLT2 inhibitor ipragliflozin affects cardiovascular activity in non-diabetic Sprague-Dawley (SD) rats and Spontaneously Diabetic Torii (SDT) fatty rats in two studies, a urine collection study and a telemetry study. In the former study, urine was collected for 24 hours after a single oral dose of ipragliflozin...
November 28, 2018: Clinical and Experimental Pharmacology & Physiology
Blythe D Shepard, Hermann Koepsell, Jennifer L Pluznick
Olfactory receptors (ORs) are G protein-coupled receptors which serve to detect odorants in the nose. Additionally, these receptors are expressed in other tissues where they have functions outside of the canonical smell response. Olfactory Receptor 1393 (Olfr1393) was recently identified as a novel regulator of sodium glucose co-transporter 1 (Sglt1) localization in the renal proximal tubule. Glucose reabsorption in the proximal tubule (via Sglt1 and Sglt2) has emerged as an important contributor to the development of diabetes...
November 28, 2018: American Journal of Physiology. Renal Physiology
Satoru Kuriyama
This communication provides a current overview on the renal protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diabetics. Following the epoch-making publications, the CANVAS Program and the EMPA-REG OUTCOME trial, numerous literature has discussed the mechanisms by which SGLT2 inhibition exerts its cardio-renal protective effects. Some of them reached agreement, while others did not. This review focuses on the hemodynamic aspect and the remaining potential factors relevant to the renal protection which have not been so much taken up by other review papers...
November 26, 2018: Clinical and Experimental Nephrology
Ken Lee Chin, Richard Ofori-Asenso, Ingrid Hopper, Thomas G von Lueder, Christopher M Reid, Sophia Zoungas, Bing H Wang, Danny Liew
There is growing evidence from phase III randomised clinical trials of the cardiovascular benefits of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with diabetes mellitus. It is hypothesised that these benefits are mediated by mechanisms other than glucose control. To address this, we performed a systematic review of data from preclinical studies examining the direct cardioprotective effects of SGLT2 inhibitors. Medline, EMBASE, CINAHL and International Pharmaceutical Abstracts databases were searched for preclinical studies that examined the potential cardioprotective effects of SGLT2 inhibitors...
November 26, 2018: Cardiovascular Research
Mattia Galli, Domenico D'Amario, Carmelo Sofia, Marcello Vaccarella, Filippo Crea, Nadia Aspromonte
Heart failure (HF) affects approximately 2% of the population worldwide, remaining a major cause of hospitalization and mortality despite innovative therapeutic approaches introduced in the past few decades. Type 2 diabetes mellitus (T2D) contributes significantly to end-organ damage and HF-related complications and is associated with worse clinical status and increased all-cause and cardiovascular mortality in patients with HF with reduced (HFrEF) or with preserved ejection fraction (HFpEF), compared to HF patients without T2D...
November 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
Kuang-Feng Chu, Jen-Shin Song, Chiung-Tong Chen, Teng-Kuang Yeh, Tsung-Chih Hsieh, Chung-Yu Huang, Min-Hsien Wang, Szu-Huei Wu, Chun-Hsu Yao, Yu-Sheng Chao, Jinq-Chyi Lee
Sodium-dependent glucose co-transporter 2 (SGLT2) inhibition has been demonstrated to efficiently control hyperglycemia via an insulin secretion-independent pathway. The unique mode of action eliminates the risk of hypoglycemia and makes SGLT2 inhibitors an attractive option for the treatment of type 2 diabetes. In a continuation of our previous studies on SGLT2 inhibitors bearing different sugar moieties, sixteen new N-glucosyl indole derivatives were designed, synthesized, and evaluated for their inhibitory activity against hSGLT2...
November 7, 2018: Bioorganic Chemistry
Xiaomin Liu, Yanmao Wang, Xiaotian Zhang, Xinju Zhang, Jing Guo, Jinbao Zhou, Yimin Chai, Zhong-Liang Ma
BACKGROUND: Diabetic wounds are refractory and very difficult to heal. We aimed to use miRNA to identify novel and specific molecular markers for diabetes mellitus (DM) diagnosis and treatment. METHODS: The expression level of miR-296-5p was determined in tissue samples of 12 DM patients. The effect of miR-296-5p on proliferation of β-cells was examined using CCK-8 and colony formation assay. The effect of miR-296-5p on cell cycle progression was analyzed using flow cytometry...
November 22, 2018: Diabetes/metabolism Research and Reviews
Alvaro Garcia-Ropero, Juan J Badimon, Carlos G Santos-Gallego
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder associated with high cardiovascular (CV) risk. Some of the therapeutic strategies are contraindicated in patients with concomitant heart disease. However, the newest antidiabetic medications, sodium-glucose cotransporter 2 (SGLT2) inhibitors, have shown to significantly reduce CV mortality and heart failure (HF) hospitalizations. The mechanism behind these surprising cardiac benefits remains unclear. Areas covered: This article reviews the pharmacokinetic, pharmacodynamics, efficacy and safety data for the different SGLT2 inhibitors...
November 21, 2018: Expert Opinion on Drug Metabolism & Toxicology
Alan Maloney, Julio Rosenstock, Vivian Fonseca
Model-based meta-analysis was used to compare glycemic control, weight changes and hypoglycemia risk across 24 antihyperglycemic drugs used to treat type 2 diabetes. Electronic searches identified 229 randomized controlled studies comprising 121,914 patients. To ensure fair and unbiased treatment comparisons, the analyses adjusted for important differences between studies, including duration of treatment, baseline glycated hemoglobin, and drug dosages. At the approved doses, glycemic control was typically greatest with glucagon-like peptide 1 receptor agonists (GLP-1RAs), and least with dipeptidyl peptidase-4 (DPP-4) inhibitors...
November 20, 2018: Clinical Pharmacology and Therapeutics
Subodh Verma, Sonia Rawat, Kim L Ho, Cory S Wagg, Liyan Zhang, Hwee Teoh, John E Dyck, Golam M Uddin, Gavin Y Oudit, Eric Mayoux, Michael Lehrke, Nikolaus Marx, Gary D Lopaschuk
SGLT2 inhibitors have profound benefits on reducing heart failure and cardiovascular mortality in individuals with type 2 diabetes, although the mechanism(s) of this benefit remain poorly understood. Because changes in cardiac bioenergetics play a critical role in the pathophysiology of heart failure, the authors evaluated cardiac energy production and substrate use in diabetic mice treated with the SGTL2 inhibitor, empagliflozin. Empagliflozin treatment of diabetic db/db mice prevented the development of cardiac failure...
October 2018: JACC. Basic to Translational Science
Michael S Kelly, Jelena Lewis, Ashley M Huntsberry, Lauren Dea, Ivan Portillo
OBJECTIVE: To review glucose-lowering efficacy and changes in renal function associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). DATA SOURCES: A literature search of MEDLINE and Cochrane databases was performed from 2000 to August 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, and chronic kidney disease...
November 17, 2018: Postgraduate Medicine
Yusuf Olgar, Belma Turan
Sodium-glucose cotransporter 2 (SGLT2)-inhibitors showed significant effect in patients with diabetes or metabolic syndrome, MetS with high cardiovascular-risk. Although the increased intracellular Zn2+ level ([Zn2+]i), oxidative stress and alterated cardiac matrix metalloproteinases (MMPs) in diabetic cardiomyopathy can intersect with different signaling pathways, the exact mechanisms are not known yet. Since either MMPs or SGLT2 have important role in cardiac-fibrosis under hyperglycemia, we aimed to examine the role of SGLT2-inhibitor dapagliflozin (DAP) on cardiac Zn2+-transporters responsible from [Zn2+]i-regulation, comparison to insulin (INS), together with MMP levels and systemic oxidative-stress-status in MetS-rats...
November 16, 2018: Canadian Journal of Physiology and Pharmacology
Habib Yaribeygi, Stephen L Atkin, Alexandra E Butler, Amirhossein Sahebkar
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are therapeutic agents that have been used recently to reduce tubular absorption of glucose, leading to enhanced glycosuria, resulting in the reduction of blood glucose and improved diabetes control. Recent data suggest that SGLT2 inhibitors have antioxidant properties that may be key to the reduction in cardiovascular death found in clinical trials. Oxidative stress is involved in the development and progression of atherosclerosis, as well as underlying diabetes complications, and may result from either increased free-radical production, a reduction in antioxidative capacity, or a combination of both...
November 15, 2018: Journal of Cellular Physiology
Zosia Kmietowicz
No abstract text is available yet for this article.
November 14, 2018: BMJ: British Medical Journal
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