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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/28408925/combination-therapy-with-a-sodium-glucose-cotransporter-2-inhibitor-and-a-dipeptidyl-peptidase-4-inhibitor-additively-suppresses-macrophage-foam-cell-formation-and-atherosclerosis-in-diabetic-mice
#2
Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, Tsutomu Hirano
Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe(-/-) ) mice...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28381459/urinary-adenosine-excretion-in-type-1-diabetes
#3
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
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
#4
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/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#5
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFA) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28244644/optimizing-the-analysis-strategy-for-the-canvas-program-a-prespecified-plan-for-the-integrated-analyses-of-the-canvas-and-canvas-r-trials
#6
Bruce Neal, Vlado Perkovic, Kenneth W Mahaffey, Greg Fulcher, Ngozi Erondu, Mehul Desai, Wayne Shaw, Gordon Law, Marc K Walton, Norm Rosenthal, Dick de Zeeuw, David R Matthews
Two large cardiovascular outcome trials of canagliflozin, comprising the CANVAS Program, will complete in early 2017: the CANagliflozin cardioVascular Assessment Study (CANVAS) and the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R). Accruing data for the sodium glucose co-transporter 2 (SGLT2) inhibitor class has identified questions and opportunities that were not apparent when the trials were designed. Accordingly, a series of modifications have been made to the planned analyses. These updates will ensure that the data from the CANVAS Program will maximize advances in scientific knowledge and patient care...
February 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28217523/safe-and-pragmatic-use-of-sodium-glucose-co-transporter-2-inhibitors-in-type-2-diabetes-mellitus-south-asian-federation-of-endocrine-societies-consensus-statement
#7
REVIEW
Sanjay Kalra, Sujoy Ghosh, A H Aamir, Md Tofail Ahmed, Mohammod Feroz Amin, Sarita Bajaj, Manash P Baruah, Uditha Bulugahapitiya, A K Das, Mimi Giri, Sonali Gunatilake, Saeed A Mahar, Md Faruque Pathan, Nazmul Kabir Qureshi, S Abbas Raza, Rakesh Sahay, Santosh Shakya, Dina Shreshta, Noel Somasundaram, Manilka Sumanatilleke, A G Unnikrishnan, Achini Madushani Wijesinghe
Diabetes prevalence shows a continuous increasing trend in South Asia. Although well-established treatment modalities exist for type 2 diabetes mellitus (T2DM) management, they are limited by their side effect profile. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) with their novel insulin-independent renal action provide improved glycemic control, supplemented by reduction in weight and blood pressure, and cardiovascular safety. Based on the clinical outcomes with SGLT2i in patients with T2DM, treatment strategies that make a "good clinical sense" are desirable...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28202943/arterial-pressure-lability-is-improved-by-sodium-glucose-cotransporter-2-inhibitor-in-streptozotocin-induced-diabetic-rats
#8
Tomoko Yoshikawa, Takuya Kishi, Keisuke Shinohara, Ko Takesue, Risa Shibata, Noriyuki Sonoda, Toyoshi Inoguchi, Kenji Sunagawa, Hiroyuki Tsutsui, Yoshitaka Hirooka
To prevent cardiovascular events in patients with diabetes mellitus (DM), it is essential to reduce arterial pressure (AP). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) prevents cardiovascular events via the depressor response in patients with DM. In the present study, we examined whether SGLT2i ameliorates AP lability in DM rats. Ten-week-old male Sprague-Dawley rats were administered a single intravenous injection of streptozotocin (50 mg kg(-1)) and were divided into three groups treated with low-dose SGLT2i, vehicle (VEH) or subcutaneously implanted insulin pellets (SGLT2i, VEH and Insulin group, respectively) for 14 days...
February 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28088910/sodium-glucose-cotransporter-2-inhibitors-sglt2i-their-role-in-cardiometabolic-risk-management
#9
Niki Katsiki, Dimitri P Mikhailidis, Michael J Theodorakis
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control without promoting hypoglycemia in the absence of exogenously administered insulin. METHODS: The present narrative review addresses the putative associations between SGLT2i and several cardiovascular (CV) and microvascular risk factors, as well as their effects on cardiac and renal function...
January 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28039605/pharmacokinetic-characteristics-and-clinical-efficacy-of-an-sglt2-inhibitor-plus-dpp-4-inhibitor-combination-therapy-in-type-2-diabetes
#10
REVIEW
André J Scheen
Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin)...
December 30, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27931088/sglt2-inhibitors-a-systematic-review-of-diabetic-ketoacidosis-and-related-risk-factors-in-the-primary-literature
#11
Kelly R Burke, Christine A Schumacher, Spencer E Harpe
STUDY OBJECTIVE: Currently only minimal information is available regarding risk factors for the development of sodium glucose cotransporter-2 inhibitor (SGLT2i)-related diabetic ketoacidosis (DKA). We aim to identify individual patient characteristics associated with cases of SGLT2i-related DKA to better describe potential risk factors. DESIGN: Systematic review of primary literature. PATIENTS: Thirty-four case reports of patients with type 1 and type 2 diabetes mellitus who developed DKA while receiving an SGLT2i...
February 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/27925353/effect-of-sodium-glucose-cotransporter-2-inhibitor-on-liver-function-tests-in-japanese-patients-with-non-alcoholic-fatty-liver-disease-and-type-2-diabetes-mellitus
#12
Yuya Seko, Yoshio Sumida, Saiyu Tanaka, Kojiroh Mori, Hiroyoshi Taketani, Hiroshi Ishiba, Tasuku Hara, Akira Okajima, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Kazuyuki Kanemasa, Kohichiroh Yasui, Shunsuke Imai, Keiji Shimada, Yoshito Itoh
AIM: No pharmacological therapies have been established for non-alcoholic fatty liver disease (NAFLD). Sodium glucose cotransporter 2 inhibitor (SGLT2I) was developed for the treatment of adults with type 2 diabetes mellitus (T2DM). The aim of this retrospective study is to evaluate the efficacy of SGLT2I in NAFLD patients with T2DM. METHODS: Twenty-four biopsy-proven NAFLD patients with T2DM who received SGLT2I for 24 weeks were retrospectively enrolled as the SGLT2I group...
November 2, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27765008/sglt2-inhibitors-in-diabetes-mellitus-treatment
#13
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/27762514/a-prospective-analysis-of-the-efficacy-and-safety-of-sodium-glucose-cotransporter-2-inhibitors-real-world-evidence-from-clinical-practice-in-india
#14
Bhavana Sosale, Aravind R Sosale, Prassanna M Kumar, Shashank R Joshi
BACKGROUND AND AIM: The number of patients with type 2 diabetes (T2DM) is increasing. Most patients with T2DM are uncontrolled and fail to achieve their target Hba1c. In recent years, newer agents such as SGLT2 inhibitors (SGLT2i) have been approved for clinical use. Though data from clinical trials and sub set analysis of Indian patients in global studies are promising, real world evidence from standard clinical practice in India is lacking. The aim of this study was to analyze the metabolic parameters in patients with T2DM on SGLT2i in real world clinical practice...
September 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27762088/preventive-effect-of-ipragliflozin-on-nocturnal-hypoglycemia-in-patients-with-type-2-diabetes-treated-with-basal-bolus-insulin-therapy-an-open-label-single-center-parallel-randomized-control-study
#15
Fumitaka Okajima, Tomoko Nagamine, Yuko Nakamura, Naomi Hattori, Hitoshi Sugihara, Naoya Emoto
The efficacy of the administration of sodium-glucose co-transporter 2 inhibitor or the co-administration of sodium-glucose co-transporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor to insulin therapy is not well known. A total of 58 patients with type 2 diabetes, admitted for glycemic control, were randomized to basal-bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring before discharge...
October 20, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27692167/peptide-based-glp-1-glucagon-co-agonists-a-double-edged-sword-to-combat-diabesity
#16
Hitesh Soni
Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral...
October 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27561923/dapagliflozin-enhances-fat-oxidation-and-ketone-production-in-patients-with-type-2-diabetes
#17
Giuseppe Daniele, Juan Xiong, Carolina Solis-Herrera, Aurora Merovci, Roy Eldor, Devjit Tripathy, Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
OBJECTIVE: Insulin resistance is associated with mitochondrial dysfunction and decreased ATP synthesis. Treatment of individuals with type 2 diabetes mellitus (T2DM) with sodium-glucose transporter 2 inhibitors (SGLT2i) improves insulin sensitivity. However, recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i. The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1) mitochondrial ATP synthesis and 2) substrate oxidation rates and ketone production...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27488726/effects-of-sglt-2-inhibitors-on-mortality-and-cardiovascular-events-a-comprehensive-meta-analysis-of-randomized-controlled-trials
#18
REVIEW
Matteo Monami, Ilaria Dicembrini, Edoardo Mannucci
AIMS: EMPAREG OUTCOME study showed a reduction in cardiovascular events in patients treated with the sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin, as compared to placebo. Other drugs of the same class are currently been investigated for cardiovascular outcomes. In the meanwhile, a re-analysis of data collected in available studies can add relevant insight. METHODS: A MEDLINE search for SGLT-2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials up to November 16, 2015...
January 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/27440828/positioning-sglt2-inhibitors-incretin-based-therapies-in-the-treatment-algorithm
#19
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/27435042/dpp-4-inhibitor-plus-sglt-2-inhibitor-as-combination-therapy-for-type-2-diabetes-from-rationale-to-clinical-aspects
#20
REVIEW
André J Scheen
Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. Area covered: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations. Expert opinion: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects...
December 2016: Expert Opinion on Drug Metabolism & Toxicology
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