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https://www.readbyqxmd.com/read/29452178/effects-of-canagliflozin-versus-glimepiride-on-adipokines-and-inflammatory-biomarkers-in-type-2-diabetes
#1
W Timothy Garvey, Luc Van Gaal, Lawrence A Leiter, Ujjwala Vijapurkar, James List, Robert Cuddihy, Jimmy Ren, Michael J Davies
OBJECTIVE: Type 2 diabetes and obesity are pro-inflammatory states associated with increased risk of cardiovascular disease. Canagliflozin, an SGLT2 inhibitor, demonstrated superiority in lowering HbA1c versus glimepiride with less hypoglycemia and greater weight reduction via loss of fat mass in a 52-week trial of type 2 diabetes patients. This post hoc, exploratory analysis assessed the effects of canagliflozin versus glimepiride on select adipokines, inflammatory biomarkers, and chemokines...
February 13, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29424089/cardiovascular-benefits-of-sglt2-inhibition-in-diabetes-and-chronic-kidney-diseases
#2
EDITORIAL
Anita T Layton, Volker Vallon
In addition to being a leading cause of end-stage renal disease, diabetes mellitus is also associated with an elevated risk of heart failure. A new class of anti-hyperglycaemic drugs are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, which attenuate postprandial increases in blood glucose by targeting its reabsorption along the early proximal tubule and enhancing urinary glucose excretion. Because the transport of glucose and Na+ in the proximal tubule is coupled, inhibition of SGLT2 also reduces proximal tubular Na+ and fluid reabsorption, and induces natriuresis and diuresis...
February 8, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29415819/a-new-class-of-drugs-for-heart-failure-sglt2-inhibitors-reduce-sympathetic-overactivity
#3
REVIEW
Motoaki Sano
Even in the presence of excess glucose, the proximal renal tubules continue to resorb more glucose. Sodium glucose cotransporter 2 (SGLT2) inhibitors are drugs that control this "greed" (H. Ito, Keio University, Japan). Negative feedback mechanisms maintain homeostasis for various physiological functions. However, there is no negative feedback mechanism for resorption of glucose by the proximal renal tubules. When food was scarce during human evolution, not limiting nutrient reabsorption was advantageous for survival, but the opposite is true in the era of satiation...
February 4, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29402981/clinical-features-and-therapeutic-perspectives-on-hypertension-in-diabetics
#4
REVIEW
Shigehiro Katayama, Masako Hatano, Masashi Issiki
Over 50% of patients with diabetes mellitus, either type 1 or 2, ultimately develop hypertension as a complication. In diabetics, this further increases the incidence of cardiovascular disease (CVD) by 2- to 3-fold and accelerates the progression of diabetic nephropathy. Arteriosclerosis, a clinical feature of hypertension in diabetics, develops and advances from a young age. Therefore, in providing treatment, it is necessary to evaluate the degree of arteriosclerosis. Diabetic patients are encouraged to strictly control their blood glucose levels...
February 5, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29388411/-sglt2-inhibitor-or-glp-1-receptor-agonist-in-a-patient-with-type-2-diabetes-and-cardiovascular-disease
#5
A J Scheen, N Paquot
Two classes of antidiabetic agents have shown a cardiovascular and renal protection in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, and liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, were granted a reduction of major cardiovascular events and mortality after the positive results of EMPA-REG OUTCOME and LEADER outcome trials, respectively. Protection mechanisms most probably differ between the two pharmacological classes and are perhaps complementary...
January 2018: Revue Médicale de Liège
https://www.readbyqxmd.com/read/29374293/effects-of-the-sglt2-inhibitor-ipragliflozin-on-various-diabetic-symptoms-and-progression-of-overt-nephropathy-in-type-2-diabetic-mice
#6
Atsuo Tahara, Toshiyuki Takasu
Diabetic nephropathy is the leading cause of end-stage renal disease and is associated with high-cardiovascular risk and significant morbidity and mortality. The recent development of sodium-glucose cotransporter (SGLT) 2 inhibitors offers a new antidiabetic therapy via enhanced glucose excretion; however, the beneficial effect of these drugs on the development of type 2 diabetic overt nephropathy is still largely unclear. We examined the therapeutic effects of the SGLT2 inhibitor ipragliflozin on various diabetic symptoms and the progression of nephropathy in uninephrectomized type 2 diabetic mice, which exhibit not only typical diabetic symptoms, such as impaired insulin secretion, glucose intolerance, hyperglycemia, and obesity, but also overt nephropathy with decline in renal function...
January 26, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29372664/sodium-glucose-co-transporter-2-inhibitors-and-cardiovascular-outcomes-a-systematic-review-and-meta-analysis
#7
Muhammad Shariq Usman, Tariq Jamal Siddiqi, Muhammad Mustafa Memon, Muhammad Shahzeb Khan, Wasiq Faraz Rawasia, Muhammad Talha Ayub, Jayakumar Sreenivasan, Yasmeen Golzar
Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29368965/consensus-statement-by-the-american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-on-the-comprehensive-type-2-diabetes-management-algorithm-2018-executive-summary
#8
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial...
January 2018: Endocrine Practice
https://www.readbyqxmd.com/read/29368701/effect-of-glucose-lowering-therapies-on-heart-failure
#9
REVIEW
Michael Nassif, Mikhail Kosiborod
Heart failure is one of the most common comorbidities of diabetes mellitus. Glucose-lowering therapies that can prevent heart failure or improve outcomes in patients with established heart failure are of critical importance among those with type 2 diabetes. Several types of glucose-lowering drugs have been assessed in this setting. Metformin has been shown to modestly improve the outcomes of patients with heart failure, whereas the effect of insulin in those with established heart failure is less clear. The effect of sulfonylureas on improving heart failure is controversial; observational reports have suggested that they are harmful in these patients, but these data have not been confirmed in randomized, controlled trials...
January 25, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29359260/clinical-impact-of-oral-antidiabetic-medications-in-heart-failure-patients
#10
REVIEW
Alberto Palazzuoli, Elena Ceccarelli, Gaetano Ruocco, Ranuccio Nuti
Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate...
January 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29358464/mortality-reduction-in-empa-reg-outcome-trial-beyond-the-antidiabetes-effect
#11
Samy Suissa
Two recent large-scale cardiovascular outcome trials, a now common tool in assessing the safety of pharmacological treatments for type 2 diabetes, reported significant reductions in all-cause mortality. In EMPA-REG OUTCOME [BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients], patients who received the SGLT2 inhibitor empagliflozin had a notable reduction of 9.2 deaths per 1,000 per year, while LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation) found that the patients receiving the GLP-1 receptor agonist liraglutide had a reduction of 3...
February 2018: Diabetes Care
https://www.readbyqxmd.com/read/29353233/cardiovascular-safety-long-term-noncardiovascular-safety-and-efficacy-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-type-2-diabetes-mellitus-a-systemic-review-and-meta-analysis-with-trial-sequential-analysis
#12
REVIEW
Xin-Lin Zhang, Qing-Qing Zhu, Yu-Han Chen, Xue-Ling Li, Fu Chen, Jian-An Huang, Biao Xu
BACKGROUND: The cardiovascular and long-term noncardiovascular safety and efficacy of SGLT2 (sodium-glucose cotransporter 2) inhibitors have not been well documented. METHODS AND RESULTS: For cardiovascular outcomes, we performed a meta-analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient-years of follow-up. For long-term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient-years of follow-up...
January 20, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29349558/sglt2-inhibitors-and-mechanisms-of-hypertension
#13
REVIEW
Alexandros Briasoulis, Omar Al Dhaybi, George L Bakris
PURPOSE OF REVIEW: We sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone...
January 19, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29344329/major-adverse-cardiovascular-event-reduction-with-glp-1-and-sglt2-agents-evidence-and-clinical-potential
#14
REVIEW
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#15
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29330646/potential-impact-of-sglt2-inhibitors-on-left-ventricular-diastolic-function-in-patients-with-diabetes-mellitus
#16
REVIEW
Hidekazu Tanaka, Ken-Ichi Hirata
The pathogenesis of diabetes mellitus (DM)-related cardiac dysfunction is thought to be multifactorial, and possibly a key factor for the development of heart failure with preserved ejection fraction (HFpEF) in patients with DM and preserved left ventricular (LV) ejection fraction. Currently, there is no effective treatment for HFpEF, which is presented as LV diastolic dysfunction. Furthermore, it is well known that, in addition to DM, hypertension and overweight/obesity are also important factors associated with HFpEF...
January 12, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29322280/direct-cardiovascular-impact-of-sglt2-inhibitors-mechanisms-and-effects
#17
REVIEW
Abdullah Kaplan, Emna Abidi, Ahmed El-Yazbi, Ali Eid, George W Booz, Fouad A Zouein
Diabetes is a global epidemic and a leading cause of death with more than 422 million patients worldwide out of whom around 392 million alone suffer from type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel and effective drugs in managing glycemia of T2D patients. These inhibitors gained recent clinical and basic research attention due to their clinically observed cardiovascular protective effects. Although interest in the study of various SGLT isoforms and the effect of their inhibition on cardiovascular function extends over the past 20 years, an explanation of the effects observed clinically based on available experimental data is not forthcoming...
January 11, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29320602/when-metformin-is-not-enough-pros-and-cons-of-sglt2-and-dpp-4-inhibitors-as-a-second-line-therapy
#18
REVIEW
Angelo Avogaro, Elías Delgado, Ildiko Lingvay
The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have advantages over older agents. Dipeptidyl peptidase-4 inhibitors are weight neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors have additional benefits: weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. Sodium glucose cotransporter 2 inhibitors have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis...
January 10, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29306791/empagliflozin-rescues-diabetic-myocardial-microvascular-injury-via-ampk-mediated-inhibition-of-mitochondrial-fission
#19
Hao Zhou, Shuyi Wang, Pingjun Zhu, Shunying Hu, Yundai Chen, Jun Ren
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29301371/the-sodium-glucose-cotransporter-2-inhibitor-dapagliflozin-prevents-renal-and-liver-disease-in-western-diet-induced-obesity-mice
#20
Dong Wang, Yuhuan Luo, Xiaoxin Wang, David J Orlicky, Komuraiah Myakala, Pengyuan Yang, Moshe Levi
Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity...
January 3, 2018: International Journal of Molecular Sciences
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