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https://www.readbyqxmd.com/read/29226041/dapagliflozin-cardiovascular-safety-and-benefits-in-type-2-diabetes-mellitus
#1
REVIEW
Fatima Saleem
Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin, canagliflozin, and empagliflozin, are a promising new therapy in the treatment of type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia thus improving glycemic control and they offer some beneficial effects on the cardiovascular (CV) system which can benefit patients with heart failure in addition toT2DM. The United States Food and Drug Administration requires new diabetes mellitus therapies to show a CV safety profile...
October 5, 2017: Curēus
https://www.readbyqxmd.com/read/29225209/dapagliflozin-reduces-fat-mass-without-affecting-muscle-mass-in-type-2-diabetes
#2
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
AIM: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been demonstrated to improve glycemic control and reduce body weight and fat mass in type 2 diabetes mellitus (T2DM). Here, our aim was to investigate the effects of SGLT2i dapagliflozin-treatment on body muscle mass and muscle fat content in patients with T2DM. METHODS: We prospectively recruited uncontrolled (hemoglobin A1c [HbA1c] >7%) Japanese T2DM patients who had a body mass index (BMI) <35 kg/m2...
December 8, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29215196/comparison-between-sglt2-inhibitors-and-pioglitazone-as-additions-to-insulin-therapy-in-type-2-diabetes-a-systematic-review-with-an-indirect-comparison-meta-analysis
#3
Yun Kyung Cho, Ye-Jee Kim, Yu Mi Kang, Seung Eun Lee, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung
AIMS/INTRODUCTION: We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials. gov through December 2016. Randomized controlled trials (RCTs) published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in T2D patients were included...
December 7, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29213337/effectiveness-of-long-term-treatment-with-sglt2-inhibitors-real-world-evidence-from-a-specialized-diabetes-center
#4
Yotsapon Thewjitcharoen, Nalin Yenseung, Areeya Malidaeng, Soontaree Nakasatien, Phawinpon Chotwanvirat, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Thep Himathongkam
Background: Diabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29197997/class-effects-of-sglt2-inhibitors-in-mouse-cardiomyocytes-and-hearts-inhibition-of-na-h-exchanger-lowering-of-cytosolic-na-and-vasodilation
#5
Laween Uthman, Antonius Baartscheer, Boris Bleijlevens, Cees A Schumacher, Jan W T Fiolet, Anneke Koeman, Milena Jancev, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic Na+ ([Na+]c) and cytosolic Ca2+ ([Ca2+]c) concentrations through inhibition of Na+/H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+]c; (2) a structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i affect the haemodynamic and metabolic performance of isolated hearts of healthy mice...
December 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/29193543/initiation-of-dapagliflozin-and-treatment-emergent-fractures
#6
Konstantinos A Toulis, John P Bilezikian, G Neil Thomas, Wasim Hanif, Kalliopi Kotsa, Rasiah Thayakaran, Deepiksana Keerthy, Abd Tahrani, Krishnarajah Nirantharakumar
An increase in the fracture risk was reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter 2 inhibitors (SGLT2i) class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture. Therefore, we performed a population-based, open cohort study was performed (January 2013-January 2016) using The Health Improvement Network (THIN). 22,618 patients with T2DM (4,548 exposed to dapagliflozin and 18,070 under standard antidiabetic treatment, matched for age and sex) with no history of fractures at baseline...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29183654/-safety-of-sglt2-inhibitors-a-review-of-the-adverse-drug-reactions-registered-in-a-national-database
#7
O Esteban-Jiménez, C Navarro-Pemán, L Urieta-González
OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26...
November 25, 2017: Semergen
https://www.readbyqxmd.com/read/29174215/choosing-dipeptidyl-peptidase-4-inhibitors-sodium-glucose-cotransporter-2-inhibitors-or-both-as-add-ons-to-metformin-patient-baseline-characteristics-are-crucial
#8
Ronald M Goldenberg
PURPOSE: Type 2 diabetes remains a poorly managed disease, with only about half of individuals with type 2 diabetes meeting guideline-recommended glycosylated hemoglobin (HbA1C) targets. A major proportion of those who have not met HbA1C goals have an HbA1C <8.0% to 8.5%. In practice, it is quite common to have to decide between dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as add-ons to metformin to help these individuals meet their HbA1C goals...
November 22, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29168157/perioperative-implications-of-sodium-glucose-cotransporter-2-inhibitors-a-case-series-of-euglycemic-diabetic-ketoacidosis-in-three-patients-after-cardiac-surgery
#9
Aaron Lau, Simon Bruce, Erica Wang, Ron Ree, Kevin Rondi, Anthony Chau
PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) comprise the newest class of oral hypoglycemic agents approved for treating type II diabetes mellitus (DM-II). Their use, however, has been associated with the rare development of euglycemic diabetic ketoacidosis (euDKA). We present three cases of euDKA that occurred following elective coronary artery bypass grafting surgery. The role of the anesthesiologist in the prevention, diagnosis, and management of this complication is also discussed...
November 22, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/29162781/successful-withdrawal-from-dobutamine-by-canagliflozin-in-a-diabetic-patient-with-stage-d-heart-failure
#10
Masaki Nakagaito, Shuji Joho, Ryuichi Ushijima, Makiko Nakamura, Tadakazu Hirai, Koichiro Kinugawa
Patients with stage D heart failure (HF) frequently become dependent on high doses of diuretics and inotropic agents. Recently, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), an oral antidiabetic agent, has been demonstrated to have favorable effects in preventing HF. However, it remains unknown whether SGLT2i is reliable for patients with decompensated HF. We experienced a case of a patient with stage D HF for whom attempting intravenous dobutamine withdrawal was difficult even after the administration of all conventional pharmacological treatment...
November 22, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29162514/increased-sugar-intake-as-a-form-of-compensatory-hyperphagia-in-patients-with-type-2-diabetes-under-dapagliflozin-treatment
#11
Ichiro Horie, Norio Abiru, Ryoko Hongo, Takeshi Nakamura, Ayako Ito, Ai Haraguchi, Shoko Natsuda, Ikuko Sagara, Takao Ando, Atsushi Kawakami
AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) cause substantially less weight loss than would be expected based on their caloric deficits, probably due to enhanced appetite regulation known as "compensatory hyperphagia," which occurs to offset the negative energy balance caused by increased glycosuria. We examined whether any specific nutrients contributed to the compensatory hyperphagia in diabetic patients taking SGLT2i. METHODS: Sixteen patients with type 2 diabetes were newly administered dapagliflozin 5 mg daily as the experimental SGLT2i group...
November 18, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#12
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29141939/dapagliflozin-in-focal-segmental-glomerulosclerosis-a-combined-human-rodent-pilot-study
#13
Harindra Rajasekeran, Heather N Reich, Michelle A Hladunewich, Daniel Cattran, Julie A Lovshin, Yuliya Lytvyn, Petter Bjornstad, Vesta Lai, Josephine Tse, Leslie Cham, Syamantak Majumder, Bridgit B Bowskill, M Golam Kabir, Suzanne L Advani, Ian W Gibson, Manish M Sood, Andrew Advani, David Z I Cherney
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an important cause of non-diabetic chronic kidney disease (CKD). Sodium glucose cotransporter-2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in non-diabetic CKD such as FSGS. OBJECTIVE: The primary aim of this pilot study was to determine the effect of 8 weeks of dapagliflozin on GFR in humans and in experimental FSGS...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29133607/cardiovascular-outcomes-and-risks-after-initiation-of-a-sodium-glucose-co-transporter-2-inhibitor-results-from-the-easel-population-based-cohort-study
#14
Jacob A Udell, Zhong Yuan, Toni Rush, Nicholas M Sicignano, Michael Galitz, Norman Rosenthal
Background : Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose co-transporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual endpoints or safety concerns. Methods : We performed a population-based cohort study among type 2 diabetes patients with established cardiovascular disease newly initiated on antihyperglycemic agents (AHAs) within the US Department of Defense Military Health System between 4/1/2013 and 12/31/2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite endpoint of all-cause mortality (ACM) and hospitalization for heart failure (HHF) event, major adverse cardiovascular events (MACE; defined as ACM, nonfatal myocardial infarction, and nonfatal stroke), and individual endpoints were evaluated using conditional Cox models comparing new SGLT2i users with other AHAs...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29081625/sodium-glucose-transporter-2-inhibitors-and-diabetic-ketoacidosis-in-three-patients-with-diabetes-underlying-causation
#15
Jordan L Kelley, Matthew Strum, Daniel M Riche, Andrew M Chandler
Sodium glucose transporter 2 inhibitors (SGLT2i) inhibit the reabsorption of glucose in the renal tubules reducing glycemia and increasing glucosuria. The increased glucosuria causes a shift in normal flora and colonization of pathogenic microorganisms leading to an increase in mycotic genital infections. Recent Food and Drug Administration reported cases of diabetic ketoacidosis (DKA) after initiation of SGLT2i probes the question of safety with such agents. The mechanisms of ketoacidosis and the breakdown of lipids are often misunderstood, and blame is placed on lack of insulin or on medications used to treat diabetes...
July 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/29076040/sglt2-inhibitors-through-the-windows-of-empa-reg-and-canvas-trials-a-review
#16
REVIEW
Ashu Rastogi, Anil Bhansali
EMPA-REG OUTCOME and CANVAS trials were designed to study the cardiovascular safety of empagliflozin and canagliflozin, respectively. Both studies were sufficiently powered to study the non-inferiority for cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (DM) and showed superiority for major adverse cardiovascular events and composite renal outcomes independent of glycemic control. Further, all patients in EMPA-REG had prior CV events (secondary prevention), compared to CANVAS that also included subjects with no prior CV events, indicating the beneficial effects of canagliflozin in primary prevention of CV events as well...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29068709/altered-patterns-of-early-metabolic-decompensation-in-type-1-diabetes-during-treatment-with-a-sglt2-inhibitor-an-insulin-pump-suspension-study
#17
Neha S Patel, Michelle A Van Name, Eda Cengiz, Lori R Carria, Stuart A Weinzimer, William V Tamborlane, Jennifer L Sherr
BACKGROUND: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. METHODS: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7...
November 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29053207/dpp-4-inhibitors-moderate-the-risk-of-genitourinary-tract-infections-associated-with-sglt2-inhibitors
#18
Gian Paolo Fadini, Benedetta Maria Bonora, Mayur Sarangdhar, Mauro Rigato, Angelo Avogaro
Genito-urinary tract infections (GUTI) are the most common adverse event (AE) during therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i). We evaluated whether dipeptidyl peptidase 4 inhibitors (DPP4i) moderate the risk of GUTI during therapy with SGLT2i, using two approaches. First, we screened the literature for randomized controlled trials (RCTs) directly comparing the frequency of GUTI in patients receiving a DPP4i/SGLT2i combination therapy versus those receiving a SGLT2i only. In the 5 trials we retrieved, the pooled RR for genital tract infections (GTI) in patients on a DPP4i/SGLT2i combination therapy versus those on SGLT2i alone was 0...
October 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29024278/why-do-sglt2-inhibitors-reduce-heart-failure-hospitalization-a-differential-volume-regulation-hypothesis
#19
REVIEW
K Melissa Hallow, Gabriel Helmlinger, Peter J Greasley, John J V McMurray, David W Boulton
The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28984487/dapagliflozin-and-saxagliptin-tablets-for-adults-with-type-2-diabetes
#20
André J Scheen
Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly)...
October 18, 2017: Expert Review of Clinical Pharmacology
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