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sglt2 type 1 diabetes

André J Scheen
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis...
September 28, 2016: Diabetes Research and Clinical Practice
Katsunori Suzuki, Yurie Mitsuma, Takaaki Sato, Takumi Anraku, Mariko Hatta
BACKGROUND: Some patients with type 2 diabetes mellitus (T2DM) on insulin have poor glycemic control and require add-on therapy to reach target glucose values. Increased insulin doses or the addition of an oral antidiabetic drug (OAD) may improve glycemic control, but many patients fail to achieve target values. The aim of this study was to compare the treatment efficacy and safety of three different therapies in such patients. METHODS: T2DM outpatients with poor glycemic control (HbA1c ≥ 7...
November 2016: Journal of Clinical Medicine Research
Ranjeet Prasad Dash, R Jayachandra Babu, Nuggehally R Srinivas
1. Several SGLT-2 inhibitors are in clinical use for the management of type 2 diabetes. The objectives of the current review were: a) to provide a comparative pharmacokinetics including absorption, distribution, metabolism and excretory (ADME) profiles of three SGLT2 inhibitors namely: sergliflozin, remogliflozin and ertugliflozin; b) to provide some perspectives on possible developmental issues. 2. Based on the t1/2 values observed in humans, the rank order of the three SGLT-2 inhibitors were ertugliflozin (16 h) > remogliflozin (2-4 h) >sergliflozin (1-1...
October 10, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Andrea Egger, Marius E Kraenzlin, Christian Meier
Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk...
October 5, 2016: Current Osteoporosis Reports
Soe Naing, Anapuma 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 FDA for the treatment of T2DM in the United States and other parts of the world in the last decade...
October 4, 2016: Postgraduate Medicine
Puneet Gupta, William B White
Dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose cotransporter 2 (SGLT2) inhibitors are relatively new therapies for the treatment of type 2 diabetes mellitus. Given the high prevalence of cardiovascular complications in patients with type 2 diabetes and recent concerns questioning CV safety of newer antidiabetic medications, cardiovascular safety of these medications requires evaluation. Areas covered: Cardiovascular effects of these drug classes from preclinical and clinical data as well as non-cardiovascular safety issues are delineated from literature searches covering the last decade and up to June 2016...
September 21, 2016: Expert Opinion on Drug Safety
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...
September 15, 2016: Lancet Diabetes & Endocrinology
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
Peter Mertens
Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. The new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0...
September 2016: Journal of Hypertension
Wenying Yang, Linong Ji, Zhiguang Zhou, Valerie A Cain, Kristina M Johnsson, C David Sjöström
BACKGROUND: The efficacy and safety of dapagliflozin, an SGLT2 inhibitor, has been demonstrated predominantly in Western populations. METHODS: The present analysis examined the efficacy and safety of dapagliflozin in Asian patients with type 2 diabetes mellitus (T2DM) from eight Phase IIb/III double-blind trials of up to 24 weeks, treated with placebo (N = 497), dapagliflozin 5 mg (N = 491) or dapagliflozin 10 mg (N = 465). RESULTS: Demographic and baseline characteristics were comparable across treatment groups...
September 14, 2016: Journal of Diabetes
Mathew John, Sonia Cerdas, Rafael Violante, Chaicharn Deerochanawong, Mohamed Hassanein, April Slee, William Canovatchel, Gill Hamilton
AIMS: Patients with type 2 diabetes mellitus (T2DM) have increased risk of adverse events (AEs; e.g. dehydration, hypoglycaemia) in hot weather. This analysis assessed the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with T2DM who live in hot climates. METHODS: This post hoc analysis evaluated patients with T2DM using pooled data from four 26-week, placebo-controlled studies (N=2,313) and data from a 104-week, active-controlled study (add-on to metformin vs glimepiride; N=1,450)...
September 2016: International Journal of Clinical Practice
Huilin Tang, Wei Cui, Dandan Li, Tiansheng Wang, Jingjing Zhang, Suodi Zhai, Yiqing Song
Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0...
September 6, 2016: Diabetes, Obesity & Metabolism
Angelo Avogaro, Gian Paolo Fadini, Giorgio Sesti, Enzo Bonora, Stefano Del Prato
Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed...
2016: Cardiovascular Diabetology
Annika Mellander, Martin Billger, Eva Johnsson, Anna Karin Träff, Shigeru Yoshida, Kristina Johnsson
BACKGROUND: In patients with type 2 diabetes mellitus (T2DM), dapagliflozin improves glycemic control and has a safety profile typically related to its mechanism of action. Hypersensitivity adverse events (AEs) have been reported in some patients with sodium-glucose cotransporter 2 (SGLT2) inhibitors, including a recent report of dermatological AEs in Japan. METHODS: We investigated the frequency and characteristics of hypersensitivity AEs, including potentially hypersensitivity-related skin AEs, across 21 phase IIb/III trials of dapagliflozin (N = 5936) versus active or placebo comparators (N = 3403), including the subpopulation of Asian patients (N = 1563)...
July 26, 2016: Clinical Drug Investigation
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
(no author information available yet)
The prevalence of type 2 diabetes is rising, and in 2015 more than 5% of adults in the UK were affected by this condition.(1,2) Management of type 2 diabetes includes encouraging lifestyle changes (increased exercise, modification of diet and smoking cessation) alongside the provision of medication to minimise long-term complications and manage blood sugar control while avoiding unwanted effects of drug treatment.(3) Of particular importance, people with type 2 diabetes are at increased risk of cardiovascular disease, and therefore the aims of treatment also include modification of associated risk factors...
July 2016: Drug and Therapeutics Bulletin
H L Tang, D D Li, J J Zhang, Y H Hsu, T S Wang, S D Zhai, Y Q Song
AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs)...
July 13, 2016: Diabetes, Obesity & Metabolism
Yoon-Kyung Chang, Hyunsu Choi, Jin Young Jeong, Ki-Ryang Na, Kang Wook Lee, Beom Jin Lim, Dae Eun Choi
Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated with or without SGLT2 inhibitor to investigate cell survival, the apoptosis signal pathway, and the induction of hypoxia-inducible factor 1 (HIF1) and associated proteins...
2016: PloS One
Gianluigi Savarese, Carmen D'Amore, Massimo Federici, Fabiana De Martino, Santo Dellegrottaglie, Caterina Marciano, Francesca Ferrazzano, Teresa Losco, Lars H Lund, Bruno Trimarco, Giuseppe M C Rosano, Pasquale Perrone-Filardi
BACKGROUND: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis. METHODS: Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included...
October 1, 2016: International Journal of Cardiology
R W Coch, J B Green
AIMS: The increased risk of cardiovascular disease in patients with type 2 diabetes has been known for many years. However, until recently the cardiovascular (CV) impact of glucose lowering strategies has been inadequately understood. Major clinical trials have now investigated the impact of intensification of glycemic control upon CV outcomes, as well as the CV effects of glucose management with newer antihyperglycemic agents. DATA SYNTHESIS: Key findings from recently completed CV outcomes trials of dipeptidyl peptidase-4 (DPP4) inhibitors, GLP-1 receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors completed thus far are reviewed and summarized...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
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