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https://www.readbyqxmd.com/read/28440009/sodium-glucose-co-transporter-2-inhibitors-for-type-2-diabetes-mellitus-an-overview-for-the-primary-care-physician
#1
REVIEW
Paresh Dandona, Ajay Chaudhuri
AIMS: Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic agents in type 2 diabetes mellitus (T2DM). This review examines their mechanism of action and provides an overview of safety and efficacy from the main studies of SGLT2 inhibitors marketed in the United States and Europe, namely, canagliflozin, dapagliflozin and empagliflozin. METHODS: We searched the PubMed database to identify relevant publications on the mechanism of action of SGLT2 inhibitors and clinical trial reports...
April 24, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28432726/combination-therapy-with-glp-1-receptor-agonist-and-sglt2-inhibitor
#2
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
#3
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
#4
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/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
#5
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/28395981/mechanisms-linking-empagliflozin-to-cardiovascular-and-renal-protection
#6
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
#7
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/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#8
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
#9
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/28383856/-dapagliflozin-forxiga%C3%A2-sglt-2-cotransporter-inhibitor-as-glucose-lowering-agent-in-type-2-diabetes
#10
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
#11
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/28376855/effects-of-the-sglt2-inhibitor-dapagliflozin-on-hdl-cholesterol-particle-size-and-cholesterol-efflux-capacity-in-patients-with-type-2-diabetes-a-randomized-placebo-controlled-trial
#12
Gian Paolo Fadini, Benedetta Maria Bonora, Giancarlo Zatti, Nicola Vitturi, Elisabetta Iori, Maria Cristina Marescotti, Mattia Albiero, Angelo Avogaro
BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce glucose levels, body weight, and blood pressure, possibly resulting in cardiovascular protection. In phase III trials, SGLT2i were shown to increase HDL cholesterol. We aimed to evaluate whether the SGLT2i dapagliflozin affects HDL function in a randomized placebo-controlled trial. METHODS: Thirty-three type 2 diabetic patients were randomized to receive dapagliflozin 10 mg or placebo for 12 weeks on top of their glucose lowering medications...
April 4, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28352212/canagliflozin-in-the-treatment-of-type-2-diabetes-an-evidence-based-review-of-its-place-in-therapy
#13
REVIEW
Thomas Karagiannis, Eleni Bekiari, Apostolos Tsapas
INTRODUCTION: Deciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium-glucose co-transporter 2 (SGLT2) inhibitors. AIM: The aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes. EVIDENCE REVIEW: Compared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0...
2017: Core Evidence
https://www.readbyqxmd.com/read/28351176/the-use-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-type-2-diabetes-and-hypertension-a-focus-on-african-american-populations
#14
David S Kountz
Diabetes, hypertension, and severe kidney disease are all disproportionately prevalent in African-Americans. Clinical trials data from type 2 diabetes (T2D) patients have demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors have a positive effect on cardiovascular risk factors - such as improved blood glucose control, reduced body weight, and reduced blood pressure - and also support a possible renal-protective role for SGLT2 inhibitors. The EMPA-REG OUTCOME(®) trial revealed that empagliflozin was associated with reduced adverse cardiovascular and renal outcomes...
April 10, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28332871/sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-inhibition-promise-of-a-dynamic-duo
#15
Ildiko Lingvay
OBJECTIVE: This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM). METHODS: We conducted a non-systematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States. RESULTS: SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiological abnormalities present in T2DM without overlapping toxicities...
March 23, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28324484/sodium-glucose-co-transporter-2-sglt2-inhibitor-comparing-trial-data-and-real-world-use
#16
Andrew McGovern, Michael Feher, Neil Munro, Simon de Lusignan
INTRODUCTION: The first cardiovascular safety trial in the sodium-glucose co-transporter-2 (SGLT2) inhibitor drug class, the Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, demonstrated significant cardiovascular risk reduction with empagliflozin. It is currently not clear what proportions of people with type 2 diabetes (T2DM) have the same high cardiovascular risk as those included in the trial, and will therefore be likely to experience the same cardiovascular benefit...
April 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28324025/clinical-and-genetic-features-of-patients-with-type-2-diabetes-and-renal-glycosuria
#17
Siqian Gong, Jiandong Guo, Xueyao Han, Meng Li, Lingli Zhou, Xiaoling Cai, Yu Zhu, Yingying Luo, Simin Zhang, Xianghai Zhou, Yumin Ma, Linong Ji
Context: A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was recently reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. Mutations in SLC5A2 and HNF1A are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood. Objective: To assess the clinical features of T2DM patients with renal glycosuria and those with low urinary glucose excretion (LUGE) and identify variants in the coding regions of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM...
January 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322073/sglt2-inhibitor-dpp-4-inhibitor-combination-therapy-complementary-mechanisms-of-action-for-management-of-type-2-diabetes-mellitus
#18
Jayant Dey
Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence...
April 3, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#19
REVIEW
Pieter Martens, Chantal Mathieu, Frederik H Verbrugge
This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#20
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
April 2017: Trends in Cardiovascular Medicine
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