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SGLT2 inhibitors

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https://www.readbyqxmd.com/read/28432726/combination-therapy-with-glp-1-receptor-agonist-and-sglt2-inhibitor
#1
REVIEW
Ralph A DeFronzo
The SGLT2 inhibitors (SGLTi) and glucagon-like-1 receptor agonists (GLP-1 RAs) effectively reduce HbA1c, but via very different mechanisms, making them an effective duet for combination therapy. Recently, drugs in both of these antidiabetic classes have been shown to reduce cardiovascular events, most likely by different mechanisms. SGLT2i appear to exert their CV protective actions by hemodynamic effects, while GLP-1 RAs work via anti-atherogenic/anti-inflammatory mechanisms, raising the possibility that combined therapy with these two classes may produce additive CV benefits...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#2
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28431476/a-consensus-statement-for-the-clinical-use-of-the-renal-sodium-glucose-co-transporter-2-inhibitor-dapagliflozin-in-patients-with-type-2-diabetes-mellitus
#3
A Avogaro, A Giaccari, P Fioretto, S Genovese, F Purrello, F Giorgino, S Del Prato
The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin ...
April 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28427104/pharmacokinetics-and-pharmacodynamics-of-tofogliflozin-a-selective-sglt2-inhibitor-in-healthy-male-subjects
#4
Nahoko Kasahara-Ito, Hiroyuki Fukase, Yoichiro Ogama, Tomohisa Saito, Yasuhiro Ohba, Sumire Shimada, Yasuki Takano, Tomoko Ichihara, Kimio Terao, Noboru Nakamichi, Yuji Kumagai, Sachiya Ikeda
Tofogliflozin is a selective oral inhibitor of sodium-glucose co-transporter 2 for treatment of type 2 diabetes mellitus. The pharmacokinetics, pharmacodynamics, and safety of tofogliflozin were investigated in healthy male subjects. Three studies were conducted: single-ascending dose study (10-640 mg) in 56 Japanese and 24 Caucasian subjects; multiple-ascending dose study (2.5-80 mg once daily for 7 days) in 24 Japanese subjects; and food-effect study (20-40 mg) in 30 Japanese subjects. Tofogliflozin was absorbed rapidly and eliminated from the systemic circulation with a t1/2 of 5-6 h...
April 20, 2017: Drug Research
https://www.readbyqxmd.com/read/28417527/effects-of-dapagliflozin-on-insulin-requirement-glucose-excretion-and-%C3%A3-hydroxybutyrate-levels-are-not-related-to-baseline-hba1c-in-youth-with-type-1-diabetes
#5
Torben Biester, Baerbel Aschemeier, Maryam Fath, Marcel Frey, Markus F Scheerer, Olga Kordonouri, Thomas Danne
Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into three baseline HbA1c categories (<7.5%, 7.5 to 9.0% or >9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels between 160-220 mg/dl...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28403877/a-comparison-of-effects-of-dpp-4-inhibitor-and-sglt2-inhibitor-on-lipid-profile-in-patients-with-type-2-diabetes
#6
Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Tae-Seok Lim, Ki-Ho Song, Ki-Dong Yoo, Yu-Bae Ahn, Seung-Hyun Ko
BACKGROUND: Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. METHODS: From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28403850/rationale-and-design-of-a-multicenter-placebo-controlled-double-blind-randomized-trial-to-evaluate-the-effect-of-empagliflozin-on-endothelial-function-the-emblem-trial
#7
RANDOMIZED CONTROLLED TRIAL
Atsushi Tanaka, Michio Shimabukuro, Yosuke Okada, Isao Taguchi, Minako Yamaoka-Tojo, Hirofumi Tomiyama, Hiroki Teragawa, Seigo Sugiyama, Hisako Yoshida, Yasunori Sato, Atsushi Kawaguchi, Yumi Ikehara, Noritaka Machii, Tatsuya Maruhashi, Kosuke R Shima, Toshinari Takamura, Yasushi Matsuzawa, Kazuo Kimura, Masashi Sakuma, Jun-Ichi Oyama, Teruo Inoue, Yukihito Higashi, Shinichiro Ueda, Koichi Node
BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by systemic metabolic abnormalities and the development of micro- and macrovascular complications, resulting in a shortened life expectancy. A recent cardiovascular (CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and all-cause mortality and hospitalization for heart failure in patients with T2DM and established CV disease (CVD)...
April 12, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28399981/efficacy-and-safety-of-sglt2-inhibitors-in-patients-with-type-1-diabetes-a-meta-analysis-of-randomized-controlled-trials
#8
Yang Yingying, Pan Hui, Wang Bo, Chen Shi, Zhu Huijuan
Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2 (SGLT2) inhibitor-SGLT2 inhibitors, in combination with insulin for type 1 diabetes mellitus (T1DM). Methods We searched Medline, Embase, and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration (FDA) data and ClinicalTrials (http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria: randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin (HbA1c) levels were between 7% and 12%...
April 10, 2017: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28395981/mechanisms-linking-empagliflozin-to-cardiovascular-and-renal-protection
#9
Pasquale Perrone-Filardi, Angelo Avogaro, Enzo Bonora, Furio Colivicchi, Paola Fioretto, Aldo Pietro Maggioni, Giorgio Sesti, Ele Ferrannini
In patients with type 2 diabetes mellitus (T2DM), the main cause of morbidity and mortality is cardiovascular (CV) disease. Diabetic kidney disease, which develops in approximately 40% of patients with T2DM, further increases the risk of CV-related morbidity and mortality. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin, which provides effective glycaemic control as either monotherapy or as an add-on to other glucose-lowering agents in patients with T2DM, was also shown to improve CV and renal outcomes in the large, randomised, placebo-controlled EMPA-REG OUTCOME trial in patients with T2DM at high risk of CV events...
March 23, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28395977/sglt2-inhibitors-in-type-2-diabetes-the-remaining-questions
#10
REVIEW
Rajesh Rajput, Jignesh Ved
As the SGLT2-i therapy progressively carves out a forte in the management of diabetes, multiple equally significant questions justly occupy the medical mind. Aspects pertinent to the influence of this therapy on the renal pathophysiology, the prevention of cardiovascular disease, and considerations for their safe use, hold immense relevance to clinical practice. This review attempts to make an appropriate clinical interpretation of the existing evidence, to evolve a practical perspective on some of these yet unanswered aspects...
March 31, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28395380/streptozotocin-treated-high-fat-fed-mice-a-new-type-2-diabetes-model-used-to-study-canagliflozin-induced-alterations-in-lipids-and-lipoproteins
#11
Tian Yu, Mitchell J Sungelo, Ira J Goldberg, Hong Wang, Robert H Eckel
The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism...
April 10, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28395363/natural-products-as-lead-compounds-for-sodium-glucose-cotransporter-sglt-inhibitors
#12
Wolfgang Blaschek
Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs)...
April 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28392860/the-effect-of-tofogliflozin-treatment-on-postprandial-glucose-and-lipid-metabolism-in-japanese-men-with-type-2-diabetes-a-pilot-study
#13
Hirokazu Kakuda, Junji Kobayashi, Masaru Sakurai, Masahiro Kakuda, Noboru Takekoshi
BACKGROUND: Postprandial hyperglycemia and hyperlipidemia are highly related to the development of atherosclerosis. Sodium/glucose cotransporter-2 (SGLT2) inhibitors have attracted attention as a new class of anti-diabetic agents for the treatment of type 2 diabetes. We investigated the effect of tofogliflozin on postprandial glucose and lipid metabolism in Japanese male patients with type 2 diabetes. METHODS: Ten Japanese men with type 2 diabetes (average age 66...
May 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28391776/mechanism-of-the-blood-pressure-lowering-effect-of-sodium-glucose-cotransporter-2-inhibitors-in-obese-patients-with-type-2-diabetes
#14
Shin Kawasoe, Yukiko Maruguchi, Shoko Kajiya, Hitoshi Uenomachi, Masaaki Miyata, Mariko Kawasoe, Takuro Kubozono, Mitsuru Ohishi
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to have BP-lowering effect in addition to blood glucose-lowering effect, however, its mechanism is still unknown. This study aimed to investigate the mechanism of blood pressure (BP) lowering effects of SGLT2 inhibitors using 24-h urinary collection in obese type 2 diabetes patients. METHODS: Twenty patients with type 2 diabetes (age 48.2 ± 10.7 years, BMI 33.0 ± 4.9 kg/m(2)) were enrolled...
April 10, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#15
M Kim, E J Lee, H M Shin, H S Jung, T K Kim, T N Kim, M J Kwon, S H Lee, B D Rhee, J H Park
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia...
April 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28391552/effect-of-empagliflozin-on-cardiac-biomarkers-in-a-zebrafish-model-of-heart-failure-clues-to-the-empa-reg-outcome-trial
#16
Xingjuan Shi, Subodh Verma, Junghwa Yun, Koroboshka Brand-Arzamendi, Krishna K Singh, Xiangdong Liu, Ankit Garg, Adrian Quan, Xiao-Yan Wen
The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was recently reported to reduce heart failure-associated hospitalizations and cardiovascular mortality amongst individuals with type 2 diabetes at high cardiovascular risk. We sought to elucidate the underlying mechanism(s) for these protective effects using a validated zebrafish heart failure model to evaluate the impact of empagliflozin on the expression of biomarkers of heart failure and mortality. We used aristolochic acid (AA) to induce heart failure in developing cmlc2::GFP transgenic zebrafish embryos and monitored BNP signaling in nppb::Luc transgenic zebrafish with a luciferase reporter assay...
April 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28387100/-about-the-choice-between-a-dpp-4-inhibitor-and-a-sglt-2-inhibitor-tor-treating-type-2-diabetes
#17
REVIEW
A J Scheen, N Paquot
Two new classes of oral antidiabetic agents play an increasing role in the management of type 2 diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and sodiumglucose cotransporters type 2 (SGLT2) inhibitors (gliflozins). After failure of a monotherapy with metformin (first pharmacological choice in type 2 diabetes), both may offer an alternative to the add-on of a sulphonylurea, especially in patients at risk of hypoglycaemia. However, the choice between a DPP-4 inhibitor and a SGLT2 inhibitor is not easy and should be oriented based upon the individual patient characteristics...
December 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28383856/-dapagliflozin-forxiga%C3%A2-sglt-2-cotransporter-inhibitor-as-glucose-lowering-agent-in-type-2-diabetes
#18
REVIEW
A J Scheen
Dapagliflozin, a specific inhibitor of sodium-glu¬cose cotransporters type 2 (SGLT2, inhibits glucose reabsorp¬tion in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c), with a minor risk of hypoglycaemia, a weight reduction and a reduction in arterial blood pressure. The efficacy of empagliflozin on HbA1c reduction increases according to the level of hyper¬glycaemia but decreases in patients with renal insufficiency...
October 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28383832/-cardiovascular-and-renal-protection-of-patients-with-type-2-diabetes-focus-after-empa-reg-outcome-and-leader
#19
REVIEW
A J Scheen, L Piérard, J-M Krzesinski, N Paquot
Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with T2D and high cardiovascular risk : empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER. Both medications showed a significant reduction in major cardiovascular events (-14 and -13 %, respectively), cardiovascular mortality (-38 and -22%), all-cause mortality (-32 and -15 %) and renal events (-39 et -22 %)...
September 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28381459/urinary-adenosine-excretion-in-type-1-diabetes
#20
Harindra Rajasekeran, Yuliya Lytvyn, Andrea Bozovic, Julie Lovshin, Eleftherios Diamandis, Daniel Cattran, Mansoor Husain, Bruce A Perkins, Andrew Advani, Heather N Reich, Vathany Kulasingam, David Z I Cherney
INTRODUCTION: In experimental models of diabetes, augmented sodium-glucose cotransport-2 (SGLT2) activity diminishes sodium (Na+) delivery at the macula densa. As a result, less vasoconstrictive adenosine is generated, leading to afferent arteriolar vasodilatation and hyperfiltration. The measurement and significance of urinary adenosine in humans has not been extensively examined in states of renal hemodynamic impairment, like that of diabetes. OBJECTIVE: Our aim was to validate a method for urine adenosine quantification in humans and perform an exploratory post-hoc analysis to determine whether urinary adenosine levels change dynamically in response to natriuresis in patients with type 1 diabetes (T1D) before and after treatment with the SGLT2 inhibitor (SGLT2i) empagliflozin...
April 5, 2017: American Journal of Physiology. Renal Physiology
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