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https://www.readbyqxmd.com/read/29157798/euglycemic-diabetic-ketoacidosis-secondary-to-dapagliflozin-use-a-case-report
#1
Felicity Brown, Tamara McColl
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a novel class of oral antihyperglycemic agents. They are associated with rare cases of euglycemic diabetic ketoacidosis (DKA), which presents a diagnostic challenge in the emergency department (ED) and potentially severe consequences if missed. CASE REPORT: A 53-year-old man with type 2 diabetes mellitus and a recent Roux-en-Y gastric bypass surgery presented to the ED with nausea, vomiting, and generalized abdominal pain...
November 17, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29154936/antidiabetic-and-antiobesity-effects-of-sglt2-inhibitor-ipragliflozin-in-type-2-diabetic-mice-fed-sugar-solution
#2
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
Obesity due to excessive calorie intake is a known aggravating factor contributing to the development and progression of type 2 diabetes. Recently, excessive intake of sugar-sweetened beverages has presented challenges in stemming the tide of obesity. Here, we investigated the possible effects of sugar solution intake on the antidiabetic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in type 2 diabetic mice that were fed ordinary drinking water, water + glucose solution, or water + sucrose solution...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#3
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#4
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#5
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29139146/effects-of-the-sodium-glucose-cotransporter-2-sglt2-inhibitor-velagliflozin-a-new-drug-with-therapeutic-potential-to-treat-diabetes-in-cats
#6
M Hoenig, M Clark, D J Schaeffer, D Reiche
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume...
November 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29134558/development-of-hyperkalemia-following-treatment-with-dapagliflozin-dapa-in-a-patient-with-type-2-diabetes-after-bilateral-adrenalectomy
#7
Daichi Miyaoka, Akihiro Tsuda, Noriyuki Hayashi, Norikazu Toi, Akiyo Yamasaki, Yuki Nagata, Shinya Nakatani, Masafumi Kurajoh, Shinsuke Yamada, Tomoaki Morioka, Yasuo Imanishi, Masanori Emoto, Masaaki Inaba
Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is known to have a beneficial diuretic effect, in addition to a glucose-lowering effect. Although SGLT2 inhibitor has been reported, the increase of hyperkalemia in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors, their mechanism of action is unclear. We report the first case of a type 2 diabetes (T2DM) patient with potential mineralocorticoid deficiency who developed hyperkalemia after administration of DAPA...
November 13, 2017: CEN Case Reports
https://www.readbyqxmd.com/read/29132091/effect-of-anti-diabetic-drugs-on-bone-metabolism-evidence-from-preclinical-and-clinical-studies
#8
REVIEW
Mohammad Adil, Rashid Ali Khan, Abul Kalam, Shiva Kumar Venkata, Amit Dattatraya Kandhare, Pinaki Ghosh, Manju Sharma
Diabetes mellitus is associated with abnormal bone health and an increased risk of fracture even though patients have normal or higher BMD. The mechanisms behind diabetes mellitus- induced various skeletal disorders remain unclear. Anti-diabetic drugs may have negative or positive impact on bone metabolism. For instance, thiazolidinediones increases the bone loss and risk of fracture possibly through PPARγ activation in bone marrow cells and hamper osteoblastogenesis via decreasing Runx2 transcription factor, IGF-1 and Wnt signalling pathways...
May 25, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127757/-gliflozins-slow-down-the-progression-of-diabetic-kidney-disease
#9
Vladimír Tesař, Jan Vachek
Until recently progression of diabetic kidney disease could have been slowed down only by the inhibition of the renin-angiotensin system. Inhibitors of SGLT2 (sodium-glucose transporter 2) in the proximal tubulus of the kidney induce natriuresis and by the activation of the tubuloglomerular feedback increase the tone of the afferent arteriole and decrease the glomerular pressure. Empagliflozin in the study EMPA-REG Outcome significantly decreased the risk of progression of diabetic kidney disease and further analyses also demonstrated its potent antiproteinuric effect...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29120659/-antidiabetic-drugs-and-their-effect-on-bone
#10
Peter Jackuliak, Martin Kužma, Juraj Payer
It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus are at an increased risk of bone fractures. Today we have several groups of effective and save antidiabetic drugs, which are very given often in combination. Although diabetes-related complications are important in the etiology, the effects of medications on bone metabolism and fracture risk should not be neglected, because the diabetes medication may affect also bone health and fracture risk...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29110406/switching-from-low-dose-thiazide-diuretics-to-sglt2-inhibitor-improves-various-metabolic-parameters-without-affecting-blood-pressure-in-subjects-with-type-2-diabetes-and-hypertension
#11
Tomohiko Kimura, Junpei Sanada, Masashi Shimoda, Hidenori Hirukawa, Yoshiro Fushimi, Momoyo Nishioka, Tomoe Kinoshita, Seizo Okauchi, Atsushi Obata, Kenji Kohara, Fuminori Tatsumi, Shinji Kamei, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
AIM/INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT2) inhibitors function to increase urinary glucose excretion and improve glycemic control in subjects with type 2 diabetes mellitus. SGLT2 inhibitors as well as diuretics increase urinary volume which leads to the reduction of blood pressure. The aim of this study was to compare the effects of SGLT2 inhibitor and thiazide diuretic on blood pressure, metabolic parameters and body mass composition. MATERIALS AND METHODS: A total of 31 subjects were enrolled in this study...
November 7, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29101501/severe-hypernatraemic-dehydration-and-unconsciousness-in-a-care-dependent-inpatient-treated-with-empagliflozin
#12
Georg Gelbenegger, Nina Buchtele, Christian Schoergenhofer, Martin Roeggla, Michael Schwameis
A 66-year-old Caucasian male became unconscious 2 weeks after initiation of add-on therapy with empagliflozin for poorly controlled type 2 diabetes mellitus. The inpatient had recently suffered focal pontine stroke, rendering him bedridden and requiring increased nursing care, including assistance with drinking. The patient had received empagliflozin 10 mg once daily for glycaemic control. Investigations revealed hypernatraemia (164 mmol/l), a urine glucose level of 3935 mg/dl, and a creatinine level of 2...
November 3, 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29098566/clinical-factors-associated-with-initial-decrease-in-body-fat-percentage-induced-by-add-on-sodium-glucose-co-transporter-2-inhibitors-in-patient-with-type-2-diabetes-mellitus
#13
Noboru Kurinami, Seigo Sugiyama, Hiroyuki Nishimura, Ayami Morita, Akira Yoshida, Kunio Hieshima, Fumio Miyamoto, Keizo Kajiwara, Katsunori Jinnouchi, Tomio Jinnouchi, Hideaki Jinnouchi
BACKGROUND AND OBJECTIVE: Obesity is globally recognized as an important clinical problem and sodium-glucose co-transporter 2 (SGLT2) inhibitors are considered a suitable therapy for obese patients with type 2 diabetes mellitus (T2DM). We examined the clinical factors associated with initial decrease in body-fat percentage (Fat %) induced by SGLT2 inhibitors in patients with T2DM. METHODS: We retrospectively enrolled patients newly treated with SGLT2 inhibitors in addition to ongoing medications at Jinnouchi Hospital between April 2014 and December 2015...
November 2, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29094264/treating-disease-mechanisms-in-patients-with-heart-failure-and-diabetes-mellitus
#14
REVIEW
Amanda Trang, David Aguilar
PURPOSE OF REVIEW: Diabetes and heart failure commonly coexist and portend worsened prognosis than either disease alone. We explore mechanisms that may serve as potential treatment targets and review the effects of various contemporary glucose-lowering agents on heart failure outcomes. RECENT FINDINGS: Promising data has emerged on sodium-glucose cotransporter 2 (SLGT2) inhibitors as the first class of agents to improve cardiovascular mortality and heart failure outcomes in diabetic individuals both with and without established heart failure...
December 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/29084249/the-effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-the-urinary-proteome
#15
David Cherney, Bruce A Perkins, Yuliya Lytvyn, Hiddo Heerspink, María E Rodríguez-Ortiz, Harald Mischak
Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides...
2017: PloS One
https://www.readbyqxmd.com/read/29076040/sglt2-inhibitors-through-the-windows-of-empa-reg-and-canvas-trials-a-review
#16
REVIEW
Ashu Rastogi, Anil Bhansali
EMPA-REG OUTCOME and CANVAS trials were designed to study the cardiovascular safety of empagliflozin and canagliflozin, respectively. Both studies were sufficiently powered to study the non-inferiority for cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (DM) and showed superiority for major adverse cardiovascular events and composite renal outcomes independent of glycemic control. Further, all patients in EMPA-REG had prior CV events (secondary prevention), compared to CANVAS that also included subjects with no prior CV events, indicating the beneficial effects of canagliflozin in primary prevention of CV events as well...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29074329/degree-of-ketonaemia-and-its-association-with-insulin-resistance-after-dapagliflozin-treatment-in-type-2-diabetes
#17
S H Min, T J Oh, S-I Baek, D-H Lee, K M Kim, J H Moon, S H Choi, K S Park, H C Jang, S Lim
BACKGROUND: Euglycaemic ketoacidosis has been reported after sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. However, the degree of ketonaemia and its metabolic effects have not been well investigated. Our study examined the degree of ketonaemia induced by SGLT2 inhibition and its association with metabolic profiles in type 2 diabetes mellitus (T2DM). METHODS: Biochemical parameters, including insulin, glucagon, free fatty acid (FFA), β-hydroxybutyrate (BHB) and acetoacetate (ACA) levels, were measured in 119 T2DM patients after dapagliflozin treatment for>3 months, and compared with a matched control group...
October 23, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29068709/altered-patterns-of-early-metabolic-decompensation-in-type-1-diabetes-during-treatment-with-a-sglt2-inhibitor-an-insulin-pump-suspension-study
#18
Neha S Patel, Michelle A Van Name, Eda Cengiz, Lori R Carria, Stuart A Weinzimer, William V Tamborlane, Jennifer L Sherr
BACKGROUND: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. METHODS: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7...
November 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29063276/the-infamous-famous-sulfonylureas-and-cardiovascular-safety-much-ado-about-nothing
#19
REVIEW
Laurentiu M Pop, Ildiko Lingvay
PURPOSE OF REVIEW: Sulfonylureas (SUs) are one of the most commonly used glucose-lowering agents worldwide. While their efficacy is undisputed, their cardiovascular safety has been debated since the 1970's. RECENT FINDINGS: With no dedicated cardiovascular studies to definitively answer this question, observational studies and meta-analyses abound and have reported divergent results, fueling the controversy. Studies that compared SUs to metformin or newer agents, like GLP-1 agonists and SGLT2 inhibitors, suggest a difference in cardiovascular events, yet this is likely the result of beneficial effects of the latter...
October 23, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29061576/sodium-glucose-cotransporter-2-inhibition-in-heart-failure-potential-mechanisms-clinical-applications-and-summary-of-clinical-trials
#20
REVIEW
Yuliya Lytvyn, Petter Bjornstad, Jacob A Udell, Julie A Lovshin, David Z I Cherney
Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor...
October 24, 2017: Circulation
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