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Dapagliflozin

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https://www.readbyqxmd.com/read/29787616/efficacy-and-safety-of-saxagliptin-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#1
Peng Men, Xiao-Tong Li, Hui-Lin Tang, Suo-di Zhai
OBJECTIVE: To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). METHODS: A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs)...
2018: PloS One
https://www.readbyqxmd.com/read/29764222/comparative-efficacy-of-once-weekly-semaglutide-and-sglt-2-inhibitors-in-type-2-diabetic-patients-inadequately-controlled-with-metformin-monotherapy-a-systematic-literature-review-and-network-meta-analysis
#2
Rohini Sharma, Lars Wilkinson, Hrvoje Vrazic, Evan Popoff, Sandra Lopes, Steve Kanters, Eric Druyts
OBJECTIVE: Treatment intensification with additional antidiabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin. METHODS: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL...
May 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#3
REVIEW
André J Scheen
Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29727906/sequential-treatment-escalation-with-dapagliflozin-and-saxagliptin-improves-beta-cell-function-in-type-2-diabetic-patients-on-previous-metformin-treatment-an-exploratory-mechanistic-study
#4
Thomas Forst, Mohammed Khaled Alghdban, Annelie Fischer, Matthias M Weber, Stephan Voswinkel, Tim Heise, Christoph Kapitza, Leona Plum-Mörschel
We investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5±7.0 years; duration of diabetes 8.8±4.7 years; HbA1c 63.9±15.8 mmol/mol; mean±SD) were enrolled in the study. During a first treatment period (TP1) all patients received 10 mg dapagliflozin for one month, followed by the addition of 5 mg saxagliptin or placebo for another month (TP2)...
May 4, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29723443/does-dapagliflozin-affect-energy-intake-and-appetite-a-randomized-controlled-exploratory-study-in-healthy-subjects
#5
Elizabeth Bertran, Helen D Berlie, Aaron Nixon, Linda Jaber
The primary aims of this study were to assess the effects of dapagliflozin versus placebo on energy intake and appetite ratings in healthy individuals. This was a randomized, single-blind, placebo-controlled, 2-period crossover study. In each period, healthy individuals received either dapagliflozin or placebo for 2 weeks. On assessment days, participants were asked to consume a standard preload breakfast. Appetite ratings were measured with 100-mm visual analog scales immediately before and during the 4.25-hour period after breakfast...
May 3, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29707088/impact-of-dapagliflozin-therapy-on-renal-protection-and-kidney-morphology-in-patients-with-uncontrolled-type-2-diabetes-mellitus
#6
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Motoko Tanaka, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
Background: We examined whether the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin can improve urine albumin-to-creatinine ratio (UACR) associated with a reduction in body weight or body fat in patients with type 2 diabetes mellitus (T2DM). Methods: We prospectively recruited T2DM patients having inadequate glycemic control (hemoglobin A1c (HbA1c) > 7.0%) not on SGLT2i therapy. We treated the patients with add-on dapagliflozin treatment or intensification of non-SGLT2 inhibitor therapies for 6 months...
June 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29704192/sglt2-inhibition-and-heart-failure-current-concepts
#7
REVIEW
Joaquim Silva Custodio, Andre Rodrigues Duraes, Marconi Abreu, Natalia Albuquerque Rocha, Leonardo Roever
Type 2 diabetes mellitus (T2DM) is a major risk factor for several cardiovascular (CV) conditions, including heart failure (HF). However, until recently, no therapy to treat patients with diabetes could also reduce CV risks related to HF. The EMPA-REG OUTCOME trial with empagliflozin was the first to demonstrate significant cardioprotective benefits in this population. Its impressive 35% reduction in hospitalizations for HF drew the attention of the scientific community to the possibility that pharmacologic sodium-glucose cotransporter 2 (SGLT2) inhibition could be part of the armamentarium for treating patients with HF, with and without diabetes...
April 28, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29703207/sglt2-inhibition-via-dapagliflozin-improves-generalized-vascular-dysfunction-and-alters-the-gut-microbiota-in-type-2-diabetic-mice
#8
Dustin M Lee, Micah L Battson, Dillon K Jarrell, Shuofei Hou, Kayl E Ecton, Tiffany L Weir, Christopher L Gentile
BACKGROUND: Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism...
April 27, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29693360/eligibility-varies-among-the-4-sodium-glucose-cotransporter-2-inhibitor-cardiovascular-outcomes-trials-implications-for-the-general-type-2-diabetes-us-population
#9
Eric T Wittbrodt, James M Eudicone, Kelly F Bell, Devin M Enhoffer, Keith Latham, Jennifer B Green
OBJECTIVES: Guidance to industry from the FDA requires studies to evaluate the cardiovascular safety of novel type 2 diabetes (T2D) medications. Although the objectives of such cardiovascular outcomes trials (CVOTs) are similar, differences in features such as enrollment criteria present a challenge when trying to assess the applicability of these studies to real-world T2D populations. This study evaluated the proportions of US adults with T2D who met the eligibility criteria for each of the 4 sodium-glucose cotransporter-2 (SGLT2) inhibitor CVOTs...
April 2018: American Journal of Managed Care
https://www.readbyqxmd.com/read/29693359/a-retrospective-real-world-study-of-dapagliflozin-versus-other-oral-antidiabetic-drugs-added-to-metformin-in-patients-with-type-2-diabetes
#10
Huan Huang, Kelly F Bell, Ray Gani, Cathy W Tugwell, James M Eudicone, Michelle R Krukas-Hampel
OBJECTIVES: The efficacy of dapagliflozin as add-on therapy to metformin has been assessed in randomized trials. However, its effectiveness has not been assessed in a US real-world setting. METHODS: Electronic medical record (EMR) data were used to compare clinical outcomes among patients with type 2 diabetes (T2D) treated with dapagliflozin and metformin with or without other oral antidiabetic drugs (D + M ± OAD), versus metformin with at least 1 other OAD (M + OAD)...
April 2018: American Journal of Managed Care
https://www.readbyqxmd.com/read/29674332/potent-sodium-glucose-cotransporter-sglt1-2-dual-inhibition-improves-glycemic-control-without-marked-gastrointestinal-adaptation-or-colonic-microbiota-changes-in-rodents
#11
Fuyong Du, Simon A Hinke, Cassandre Cavanaugh, David Polidori, Nathanial Wallace, Thomas Kirchner, Matthew Jennis, Wensheng Lang, Gee-Hong Kuo, Micheal D Gaul, James Lenhard, Keith Demarest, Nadim J Ajami, Yin Liang, Pamela J Hornby
The sodium/glucose cotransporters (SGLT1 and SGLT2) transport glucose across the intestinal brush border and kidney tubule. Dual SGLT1/2 inhibition could reduce hyperglycemia more than SGLT2-selective inhibition in patients with type 2 diabetes. However, questions remain about altered gastrointestinal (GI) luminal glucose and tolerability, and this was evaluated in slc5a1-/- mice or with a potent dual inhibitor (compound 8; SGLT1 K i = 1.5 ± 0.5 nM 100-fold greater potency than phlorizin; SGLT2 K i = 0.4 ± 0...
June 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29672334/dapagliflozin-associated-diabetic-ketoacidosis
#12
Raja Chandra Chakinala, Anna P Chang, Shantanu Solanki, Khwaja F Haq, Ronald Cho
No abstract text is available yet for this article.
April 18, 2018: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29607968/the-sglt2-inhibitor-dapagliflozin-significantly-improves-the-peripheral-microvascular-endothelial-function-in-patients-with-uncontrolled-type-2-diabetes-mellitus
#13
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
Objective Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce cardiovascular events and decrease the body fat mass in patients with type 2 diabetes mellitus (T2DM). We examined whether or not the SGLT2-inhibitor dapagliflozin can improve the endothelial function associated with a reduction in abdominal fat mass. Methods We prospectively recruited patients with uncontrolled (hemoglobin A1c [HbA1c] >7.0%) T2DM who were not being treated by SGLT2 inhibitors. Patients were treated with add-on dapagliflozin (5 mg/day) or non-SGLT2 inhibitor medicines for 6 months to improve their HbA1c...
March 30, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29595326/a-real-world-analysis-of-glycemic-control-among-patients-with-type-2-diabetes-treated-with-canagliflozin-versus-dapagliflozin
#14
Lawrence Blonde, Charmi Patel, Brahim Bookhart, Michael Pfeifer, Yen-Wen Chen, Bingcao Wu
OBJECTIVE: This US retrospective cohort study compared the real-world effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg on HbA1c reduction in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients initiated on canagliflozin 300 mg or dapagliflozin 10 mg were identified from de-identified claims data in the Optum Clinformatics® database (1/1/2014-9/30/2016). Propensity score matching was used to create balanced cohorts. The primary outcome was proportion of patients with HbA1c <8...
March 29, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29589153/an-exploratory-study-of-dapagliflozin-for-the-attenuation-of-albuminuria-in-patients-with-heart-failure-and-type-2-diabetes-mellitus-dapper
#15
Fumiki Yoshihara, Miki Imazu, Toshimitsu Hamasaki, Toshihisa Anzai, Satoshi Yasuda, Shin Ito, Haruko Yamamoto, Kazuhiko Hashimura, Yoshio Yasumura, Kiyoshi Mori, Masataka Watanabe, Masanori Asakura, Masafumi Kitakaze
BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly...
March 28, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29588466/canagliflozin-inhibits-interleukin-1%C3%AE-stimulated-cytokine-and-chemokine-secretion-in-vascular-endothelial-cells-by-amp-activated-protein-kinase-dependent-and-independent-mechanisms
#16
Sarah J Mancini, Daria Boyd, Omar J Katwan, Anastasiya Strembitska, Tarek A Almabrouk, Simon Kennedy, Timothy M Palmer, Ian P Salt
Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29573529/effects-of-the-sglt-2-inhibitor-dapagliflozin-on-glomerular-and-tubular-injury-markers
#17
Claire C J Dekkers, Sergei Petrykiv, Gozewijn D Laverman, David Z Cherney, Ron T Gansevoort, Hiddo J L Heerspink
The mechanisms by which SGLT-2 inhibitors lower albuminuria are incompletely understood. We assessed in a post-hoc analysis of a cross-over trial the effects of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG to albumin), tubular markers (urinary KIM-1, NGAL and LFABP) and inflammatory markers (urinary MCP-1 and IL-6) to provide more insight into kidney protective effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI, 30.3%-54.8%) and eGFR by 5.1 (2.0-8.1) mL/min/1.73m2 compared to placebo...
March 24, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29573139/effects-of-exenatide-once-weekly-plus-dapagliflozin-exenatide-once-weekly-or-dapagliflozin-added-to-metformin-monotherapy-in-subgroups-of-patients-with-type-2-diabetes-in-the-duration-8-randomized-controlled-trial
#18
Juan P Frías, Elise Hardy, Azazuddin Ahmed, Peter Öhman, Serge Jabbour, Hui Wang, Cristian Guja
This analysis assessed whether responses with exenatide once weekly (QW) plus dapagliflozin (n=231), exenatide QW (n=230), or dapagliflozin (n=233) differed in key patient subpopulations of the DURATION-8 trial. Potential treatment-by-subgroup interactions for changes in glycated haemoglobin (HbA1c) and body weight after 28 weeks were evaluated among subgroups determined by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race, ethnicity, and estimated glomerular filtration rate (eGFR). Exenatide QW plus dapagliflozin reduced HbA1c and body weight across all subgroups; least-squares mean (LSM) reductions ranged from -8...
March 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29573118/sglt2-inhibitors-and-stroke-risk-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#19
Man Guo, Jingya Ding, Jingsong Li, Jiying Wang, Ting Zhang, Cuiping Liu, Wei Huang, Yang Long, Chenlin Gao, Yong Xu
The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke risk have not been conclusively established. Therefore, we conducted a meta-analysis to evaluate the effects of SGLT2 inhibitors on stroke risk for patients with type 2 diabetes mellitus (T2DM) by searching available randomized trials published on the PubMed, Embase, CENTRAL, Web of Science, Scopus, and ClinicalTrials.gov databases. We identified 32 eligible trials enrolling 75,540 participants. The stroke incidence in groups receiving SGLT2 inhibitor monotherapy or combination therapy did not significantly differ from that in control groups, with relative risk (RR)=1...
March 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29572114/renal-outcomes-with-sodium-glucose-cotransporter-2-sglt2-inhibitor-dapagliflozin-in-obese-insulin-resistant-model
#20
Krit Jaikumkao, Anchalee Pongchaidecha, Nuttawud Chueakula, Laongdao Thongnak, Keerati Wanchai, Varanuj Chatsudthipong, Nipon Chattipakorn, Anusorn Lungkaphin
A growing body of evidence indicates that obesity and insulin resistance contribute to the progression of renal disease. This study was performed to determine the effects of dapagliflozin, a novel sodium glucose cotransporter 2 (SGLT2) inhibitor, on renal and renal organic anion transporter 3 (Oat3) functions in high-fat diet fed rats, a model of obese insulin-resistance. Twenty-four male Wistar rats were divided into two groups, and received either a normal diet (ND) (n = 6) or a high-fat diet (HFD) (n = 18) for 16 weeks...
June 2018: Biochimica et Biophysica Acta
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