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https://www.readbyqxmd.com/read/28177187/efficacy-and-safety-of-canagliflozin-as-add-on-therapy-to-teneligliptin-in-japanese-patients-with-type-2-diabetes-mellitus-results-of-a-24-week-randomised-double-blind-placebo-controlled-trial
#1
Takashi Kadowaki, Nobuya Inagaki, Kazuoki Kondo, Kenichi Nishimura, Genki Kaneko, Nobuko Maruyama, Nobuhiro Nakanishi, Hiroaki Iijima, Yumi Watanabe, Maki Gouda
AIMS: To investigate efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin administered as add-on therapy to the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial in Japanese patients with T2DM who had inadequate glycaemic control with teneligliptin. Patients were randomised to receive teneligliptin 20 mg plus either canagliflozin 100 mg (T + C, n = 70) or placebo (T + P, n = 68) once daily...
February 8, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28151518/-type-2-diabetes-treatment-and-cardiovascular-risk-what-can-we-learn-from-trials
#2
Agostino Consoli, Fabrizio Febo
Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28151517/-effects-of-glucagon-like-peptide-1-receptor-agonists-on-cardiovascular-risk-factors-and-the-cardiovascular-system
#3
Teresa Vanessa Fiorentino, Giorgio Sesti
The results of the cardiovascular outcome trials comparing the SGLT2 inhibitor empagliflozin and the glucagon-like peptide-1 receptor agonist liraglutide to placebo have been recently published. Interestingly, empagliflozin and liraglutide treatments significantly reduce cardiovascular events in subjects with type 2 diabetes. The mechanisms underlying the observed cardioprotective effects of empagliflozin and liraglutide are speculative and future studies are needed to better understand these results. However, since reduction in the primary outcome was evident 3 months after starting empagliflozin and 24 months after starting liraglutide, it is tempting to hypothesize that the cardiovascular benefits observed in diabetic patients treated with empagliflozin are due to its hemodynamic effects and to metabolic substrate shift induced by the mild and persistent hyperketonemia, while the positive effects of liraglutide treatment may be attributable to biologic changes of atherosclerotic lesions...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28128510/determinants-of-the-increase-in-fasting-plasma-ketone-concentration-during-sglt2-inhibition-in-ngt-ifg-and-t2dm-patients
#4
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
AIM: To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration RESEARCH DESIGN AND METHODS: Fasting plasma glucose, insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at 1 and 14 days after treatment with empagliflozin. RESULTS: Empagliflozin caused 38 mg/dl reduction in the fasting plasma glucose (FPG) concentration in T2DM patients...
January 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#5
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27990776/sglt2-inhibitor-use-and-dietary-carbohydrate-intake-in-japanese-individuals-with-type-2-diabetes-a-randomized-open-label-3-arm-parallel-comparative-exploratory-study
#6
Daisuke Yabe, Masahiro Iwasaki, Hitoshi Kuwata, Takuya Haraguchi, Yoshiyuki Hamamoto, Takeshi Kurose, Kiminobu Sumita, Hitoshi Yamazato, Shigeto Kanada, Yutaka Seino
This study investigated safety and efficacy of the SGLT2 inhibitor luseogliflozin under differing carbohydrate intake in Japanese individuals with type 2 diabetes (T2D). Subjects were randomly assigned to three carbohydrate-adjusted meals for 14 days (Days 1-14) [HC-HGI, 55% total energy carbohydrate (TEC) and high glycemic index (GI); HC-LGI, 55% TEC and low GI; and LC-HGI, 40% TEC and high GI]. All subjects received luseogliflozin for the last 7 days (Days 8-14); continuous glucose monitoring (CGM) before and after luseogliflozin treatment (Days 5-8 and Days 12-15); and blood tests on Days 1, 8, and 15...
December 19, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27889414/changes-in-glucose-induced-plasma-active-glucagon-like-peptide-1-levels-by-co-administration-of-sodium-glucose-cotransporter-inhibitors-with-dipeptidyl-peptidase-4-inhibitors-in-rodents
#7
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27765008/sglt2-inhibitors-in-diabetes-mellitus-treatment
#8
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/27701934/impact-of-empa-reg-outcome-%C3%A2-on-the-management-of-type-2-diabetes-mellitus-a-review-for-primary-care-physicians
#9
REVIEW
Soe Naing, Anupama Poliyedath, Stutee Khandelwal, Teresa Sigala
Cardiovascular (CV) disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have shown no significant CV benefit or increased risk of death or heart failure, with the exception of metformin. Three novel classes of glucose-lowering agents, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have been approved by the U.S. Food and Drug Administration for the treatment of T2DM in the United States and have also been available in other parts of the world in the past decade...
November 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27651331/exenatide-once-weekly-plus-dapagliflozin-once-daily-versus-exenatide-or-dapagliflozin-alone-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-monotherapy-duration-8-a-28-week-multicentre-double-blind-phase-3-randomised-controlled-trial
#10
Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Fang Dong, Peter Öhman, Serge A Jabbour
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and improve cardiovascular risk factors via different mechanisms. We aimed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin. METHODS: DURATION-8 was a 28 week, multicentre, double-blind, randomised, active-controlled phase 3 trial done at 109 sites in six countries...
December 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27633289/can-glucagon-like-peptide-1-glp1-agonists-or-sodium-glucose-co-transporter-2-sglt2-inhibitors-ameliorate-non-alcoholic-steatohepatitis-in-people-with-or-without-diabetes
#11
Vasilios G Athyros, Niki Katsiki, Asterios Karagiannis
No abstract text is available yet for this article.
September 9, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27568470/mechanisms-of-improved-glucose-handling-after-metabolic-surgery-the-big-6
#12
REVIEW
Rebecca L Paszkiewicz, Richard N Bergman
For some time, it has been clear that elevated glucose is detrimental to the organism. A plethora of medicines have been introduced to reduce the fasting and postprandial glucose levels (including insulin, glucagon-like peptide receptor 1 [GLP-1] agonists, and sodium-glucose co-transporter 2 [SGLT2] inhibitors, among others). Although these medications are useful to reduce tissue exposure to glucose, no single compound and no combination have been able to totally normalize the blood sugar. Thus, it was astonishing when it was reported that surgery of the gastrointestinal tract could not only reduce obesity but also normalize the blood sugar...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27535321/dapagliflozin-stimulates-glucagon-secretion-at-high-glucose-experiments-and-mathematical-simulations-of-human-a-cells
#13
Morten Gram Pedersen, Ingela Ahlstedt, Mickaël F El Hachmane, Sven O Göpel
Glucagon is one of the main regulators of blood glucose levels and dysfunctional stimulus secretion coupling in pancreatic A-cells is believed to be an important factor during development of diabetes. However, regulation of glucagon secretion is poorly understood. Recently it has been shown that Na(+)/glucose co-transporter (SGLT) inhibitors used for the treatment of diabetes increase glucagon levels in man. Here, we show experimentally that the SGLT2 inhibitor dapagliflozin increases glucagon secretion at high glucose levels both in human and mouse islets, but has little effect at low glucose concentrations...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27440828/positioning-sglt2-inhibitors-incretin-based-therapies-in-the-treatment-algorithm
#14
REVIEW
John P H Wilding, Surya Panicker Rajeev, Ralph A DeFronzo
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin)...
August 2016: Diabetes Care
https://www.readbyqxmd.com/read/27373139/novel-antidiabetic-drugs-and-cardiovascular-risk-primum-non-nocere
#15
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27350752/sglt2-inhibitors-or-glp-1-receptor-agonists-as-second-line-therapy-in-type-2-diabetes-patient-selection-and-perspectives
#16
REVIEW
Holly E Gurgle, Karen White, Carrie McAdam-Marx
Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM) who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM...
2016: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/27339889/pharmacology-and-therapeutic-implications-of-current-drugs-for-type-2-diabetes-mellitus
#17
REVIEW
Abd A Tahrani, Anthony H Barnett, Clifford J Bailey
Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies...
October 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27333994/changes-in-levels-of-biomarkers-associated-with-adipocyte-function-and-insulin-and-glucagon-kinetics-during-treatment-with-dapagliflozin-among-obese-type-2-diabetes-mellitus-patients
#18
Aki Okamoto, Hirohide Yokokawa, Hironobu Sanada, Toshio Naito
OBJECTIVES: This study aimed to investigate changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics after a meal tolerance test (MTT) during treatment with dapagliflozin among obese type 2 diabetes mellitus (T2DM) patients. METHODS: T2DM patients with hemoglobin A1c (HbA1c) levels >6.5 % and body mass index (BMI) >25 kg/m(2) were treated with dapagliflozin 5 mg/day for at least 12 weeks. HbA1c, body weight, ketone bodies, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) were measured before and after treatment with dapagliflozin...
September 2016: Drugs in R&D
https://www.readbyqxmd.com/read/27320223/sodium-glucose-transport-modulation-in-type-2-diabetes-and-gastric-bypass-surgery
#19
REVIEW
Gregory Baud, Violeta Raverdy, Caroline Bonner, Mehdi Daoudi, Robert Caiazzo, François Pattou
Active sodium-glucose transporters play a role to glucose homeostasis and represent novels targets for the management of type 2 diabetes (T2D). Sodium-glucose cotransporter 1 (SGLT1) is essential for intestinal glucose absorption from the lumen into enterocytes, whereas glucose reabsorption by the kidney is mainly mediated by sodium-glucose cotransporter 2 (SGLT2). SGLT2 inhibitors were developed to occlude SGLT2 glucose reabsorption pathway and cause glycosuria, thereby reducing plasma glucose concentrations...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27240541/diabetic-ketoacidosis-sodium-glucose-transporter-2-inhibitors-and-the-kidney
#20
Biff F Palmer, Deborah J Clegg, Simeon I Taylor, Matthew R Weir
Diabetic ketoacidosis is a serious metabolic condition that may occur in patients with either Type 1 or Type 2 diabetes. The accumulation of ketoacids in the serum is a consequence of insulin deficiency and glucagon excess. Sodium Glucose Transporter 2 (SGLT2) inhibitors are novel therapeutic treatments for improving glucose homeostasis in patients with diabetes. Through reductions in glucose reabsorption by the kidney, they lower serum glucose in patients with Type 2 diabetes and they improve glucose control whether used alone or in combination with other therapies...
August 2016: Journal of Diabetes and its Complications
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