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https://www.readbyqxmd.com/read/28542373/comparative-effectiveness-of-oral-antidiabetic-drugs-in-preventing-cardiovascular-mortality-and-morbidity-a-network-meta-analysis
#1
Gyeongsil Lee, Seung-Won Oh, Seung-Sik Hwang, Ji Won Yoon, Sungchan Kang, Hee-Kyung Joh, Hyuktae Kwon, Jeehyun Kim, Danbee Park
In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28538386/safety-and-efficiency-of-sglt2-inhibitor-combining-with-insulin-in-subjects-with-diabetes-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#2
Yingying Yang, Shi Chen, Hui Pan, Yun Zou, Bo Wang, Guixia Wang, Huijuan Zhu
BACKGROUND: We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes mellitus (T1DM and T2DM). METHODS: We searched Medline, Pubmed, Embase, and the Cochrane Collaboration Library from January 2010 to December 2016 without restriction of language. FDA data and Clinical Trials (http://www.clinicaltrials.gov) were also searched. Study selection, data extraction, and evaluation of risk of bias were performed by 2 persons independently...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28537992/sglt2-inhibitors-and-euglycemic-ketoacidosis
#3
Pardeep Masuta, Geetanjali Johri, Manju Paul
No abstract text is available yet for this article.
April 24, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28536852/the-role-of-sglt-2-inhibitors-as-part-of-optimal-medical-therapy-in-improving-cardiovascular-outcomes-in-patients-with-diabetes-and-coronary-artery-disease
#4
Wassim Mosleh, Abhinav Sharma, Mandeep S Sidhu, Brian Page, Umesh C Sharma, Michael E Farkouh
The optimal treatment approach to patients with coronary artery disease (CAD), including those with type 2 diabetes mellitus (T2DM), has been extensively evaluated. Several trials of stable ischemic heart disease including patients with T2DM have demonstrated that medical management is comparable to revascularization in terms of mortality and rates of major adverse cardiovascular events (MACE). There has been a growing appreciation for optimal medical therapy's (OMT) role in improving clinical outcomes. It is vital to target T2DM patients to prevent or delay MACE events through advanced OMT, ultimately delaying if not avoiding the need for revascularization...
May 24, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28536217/caution-advised-with-dapagliflozin-in-the-setting-of-male-urinary-tract-outlet-obstruction
#5
Victoria Hall, Jason Kwong, Douglas Johnson, Elif Ilhan Ekinci
We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community...
May 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28535208/sodium-glucose-cotransporter-2-in-mesangial-cells-and-retinal-pericytes-and-its-implications-for-diabetic-nephropathy-and-retinopathy
#6
Masarori Wakisaka, Tetsuhiko Nagao
Retinopathy and nephropathy are life-threatening diabetic complications that decrease patient quality of life. Although the mechanisms underlying these conditions have been extensively studied, they remain unknown. Recent reports have demonstrated the presence of SGLT2 in retinal pericytes and mesangial cells. Hyperglycemia results in functional and morphological changes in these cells, but these effects are attenuated by phlorizin, a non-selective SGLT inhibitor. Based on these findings, we hypothesized that SGLT2 plays a pivotal role in the development of diabetic nephropathy and retinopathy and that SGLT2 inhibitors may directly protect against these complications...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28528456/pharmacologic-treatment-of-dyslipidemia-in-diabetes-a-case-for-therapies-in-addition-to-statins
#7
REVIEW
Abeer Anabtawi, Patrick M Moriarty, John M Miles
PURPOSE OF REVIEW: The purpose of the study is to review the use of statins and the role of both non-statin lipid-lowering agents and diabetes-specific medications in the treatment of diabetic dyslipidemia. RECENT FINDINGS: Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200 mg/dl and HDL cholesterol levels <40 mg/dL. A number of clinical trials suggest that treatment with a fibrate may reduce cardiovascular events...
July 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28526540/sodium-dependent-glucose-transporters-sglt-in-human-ischemic-heart-a-new-potential-pharmacological-target
#8
Alessandra Di Franco, Giulia Cantini, Alessia Tani, Raffaele Coppini, Sandra Zecchi-Orlandini, Laura Raimondi, Michaela Luconi, Edoardo Mannucci
BACKGROUND: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28526185/empa-reg-outcome-the-endocrinologist-s-point-of-view
#9
Leigh Perreault
For many years, it was widely accepted that control of plasma lipids and blood pressure could lower macrovascular risk in patients with type 2 diabetes mellitus (T2DM), whereas the benefits of lowering plasma glucose were largely limited to improvements in microvascular complications. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) study demonstrated for the first time that a glucose-lowering agent, the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, could reduce major adverse cardiovascular events, cardiovascular mortality, hospitalization for heart failure, and overall mortality when given in addition to standard care in patients with T2DM at high cardiovascular risk...
May 12, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526179/empa-reg-outcome-the-nephrologist-s-point-of-view
#10
Christoph Wanner
There is increasing evidence that sodium glucose cotransporter 2 (SGLT2) inhibitors have renoprotective effects, as demonstrated by the renal analyses from clinical trials including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), CANagliflozin Treatment And Trial Analysis versus SUlphonylurea (CANTATA-SU), and the dapagliflozin renal study. The potential mechanisms responsible are likely multifactorial, and direct renovascular and hemodynamic effects are postulated to play a central role...
May 16, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28524098/sglt2-inhibitors-as-a-therapeutic-option-for-diabetic-nephropathy
#11
REVIEW
Daiji Kawanami, Keiichiro Matoba, Yusuke Takeda, Yosuke Nagai, Tomoyo Akamine, Tamotsu Yokota, Kazunori Sango, Kazunori Utsunomiya
Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium-glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28522675/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-24-hour-ambulatory-blood-pressure-a-systematic-review-and-meta-analysis
#12
REVIEW
William L Baker, Leo F Buckley, Michael S Kelly, John D Bucheit, Eric D Parod, Roy Brown, Salvatore Carbone, Antonio Abbate, Dave L Dixon
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP. METHODS AND RESULTS: We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#13
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
May 15, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28514822/-cardiovascular-effects-of-antidiabetic-therapies
#14
Katharina Laubner, Jochen Seufert
Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin...
May 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#15
REVIEW
Honghong Zou, Baoqin Zhou, Gaosi Xu
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc...
May 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28508457/effects-of-canagliflozin-on-cardiovascular-risk-factors-in-patients-with-type-2-diabetes-mellitus
#16
REVIEW
Matthew J Budoff, John P H Wilding
BACKGROUND AND AIMS: Cardiovascular disease is the most common cause of morbidity and mortality among people with type 2 diabetes mellitus (T2DM). The main contributors to cardiovascular risk in T2DM are chronic hyperglycaemia, reduced insulin sensitivity, hypertension and dyslipidaemia. Other cardiovascular risk factors include obesity and visceral adiposity, increased arterial stiffness and renal dysfunction. Results from clinical trials, including a long-term cardiovascular outcome study, have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors can provide multiple cardiometabolic benefits beyond glycaemic control including inducing mild osmotic diuresis, natriuresis and weight loss...
May 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28506912/characterization-and-comparison-of-sglt2-inhibitors-part-3-effects-on-diabetic-complications-in-type-2-diabetic-mice
#17
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#18
REVIEW
Ele Ferrannini
Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i...
May 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28502112/sglt2-inhibitor-luseogliflozin-added-to-glucagon-like-peptide-1-receptor-agonist-liraglutide-improves-glycemic-control-with-bodyweight-and-fat-mass-reductions-in-japanese-patients-with-type-2-diabetes-a-52-week-open-label-single-arm-study
#19
Yutaka Seino, Daisuke Yabe, Takashi Sasaki, Atsushi Fukatsu, Hisae Imazeki, Hidekazu Ochiai, Soichi Sakai
AIMS/INTRODUCTION: To evaluate the safety and efficacy of luseogliflozin added to liraglutide monotherapy in Japanese individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This 52-week, multicenter, open-label, single-arm clinical study enrolled Japanese patients who had inadequate glycemic control with diet/exercise and liraglutide monotherapy. Major efficacy endpoints included the changes from baseline in HbA1c, fasting plasma glucose (FPG), and bodyweight...
May 14, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28500396/sglt2-inhibitors-and-diabetic-ketoacidosis-data-from-the-fda-adverse-event-reporting-system
#20
Gian Paolo Fadini, Benedetta Maria Bonora, Angelo Avogaro
AIMS/HYPOTHESIS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We first analysed the entire public FAERS up to September (third quarter [Q3]) 2016 to extract the number of reports, background indications and concomitant medications, and to calculate proportional reporting ratios (PRRs) and safety signals...
May 12, 2017: Diabetologia
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