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https://www.readbyqxmd.com/read/29766812/switching-dipeptidyl-peptidase-4-inhibitors-to-tofogliflozin-a-selective-inhibitor-of-sodium-glucose-cotransporter-2-improves-arterial-stiffness-evaluated-by-cardio-ankle-vascular-index-in-patients-with-type-2-diabetes
#1
Nobuhiro Tahara, Sho-Ichi Yamagish, Munehisa Bekki, Atsuko Tahara, Sachiyo Igata, Akihiro Honda, Yoichi Sugiyama, Tomohisa Nakamura, Jiahui Sun, Yuki Kumashiro, Takanori Matsui, Yoshihiro Fukumoto
BACKGROUND: We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in type 2 diabetes mellitus (T2DM) patients compared with an equivalent hypoglycemic agent, glimepiride. However, it remains unclear whether and how switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS: Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study...
May 15, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29751237/current-anti-diabetic-agents-and-their-molecular-targets-a-review
#2
REVIEW
Nagaraju Kerru, Ashona Singh-Pillay, Paul Awolade, Parvesh Singh
Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy. Type-I and type-II diabetes are the two clinical forms of diabetes mellitus. Type-II diabetes mellitus (T2DM) is illustrated by the abnormality of glucose homeostasis in the body, resulting in hyperglycemia...
May 3, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29737015/therapeutic-agents-targeting-cardiometabolic-risk-for-preventing-and-treating-atherosclerotic-cardiovascular-diseases
#3
Benoit J Arsenault, Nicolas Perrot, Rishi Puri
Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29732161/rapid-onset-diabetic-ketoacidosis-secondary-to-nivolumab-therapy
#4
Senhong Lee, Aparna Morgan, Sonali Shah, Peter R Ebeling
We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non-small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29717156/high-basolateral-glucose-increases-sodium-glucose-cotransporter-2-and-reduces-sirtuin-1-in-renal-tubules-through-glucose-transporter-2-detection
#5
Hiroyuki Umino, Kazuhiro Hasegawa, Hitoshi Minakuchi, Hirokazu Muraoka, Takahisa Kawaguchi, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+ -dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29696037/pharmacological-treatment-in-diabetes-mellitus-type-1-insulin-and-what-else
#6
REVIEW
Ewa Otto-Buczkowska, Natalia Jainta
The basis of treatment in autoimmune diabetes is insulin therapy; however, many clinical cases have proven that this method does not solve all problems. Trials of causal treatment including blocking the autoimmune processes and insulin-producing cells transplants were carried out. Those methods require more research to be concerned as efficient and safe ways of treatment in type 1 diabetes. The use of non-insulin adjunct treatment is a new trend. It has been successfully used in laboratories as well as clinical trials...
January 2018: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29693800/pharmacokinetics-and-pharmacodynamics-of-luseogliflozin-a-selective-sglt2-inhibitor-in-japanese-patients-with-type-2-diabetes-with-mild-to-severe-renal-impairment
#7
Yoshishige Samukawa, Masakazu Haneda, Yutaka Seino, Takashi Sasaki, Atsushi Fukatsu, Yusuke Kubo, Yuri Sato, Soichi Sakai
This open-label, parallel-group, multicenter study aimed to assess the effects of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of luseogliflozin. A single 5-mg dose of luseogliflozin was administered to Japanese patients with type 2 diabetes mellitus in the following groups: G1, normal renal function; G2, mild renal impairment; G3a, mild to moderate impairment; G3b, moderate to severe impairment; G4, severe impairment, based on estimated glomerular filtration rate (eGFR; ≥90, 60-89, 45-59, 30-44, 15-29 mL/min/1...
April 25, 2018: Clinical Pharmacology in Drug Development
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
#8
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/29669938/canagliflozin-triggers-the-fgf23-1-25-dihydroxyvitamin-d-pth-axis-in-healthy-volunteers-in-a-randomized-crossover-study
#9
Jenny E Blau, Viviana Bauman, Ellen M Conway, Paolo Piaggi, Mary F Walter, Elizabeth C Wright, Shanna Bernstein, Amber B Courville, Michael T Collins, Kristina I Rother, Simeon I Taylor
BACKGROUND: Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29667921/glycemic-control-of-type-2-diabetes-mellitus-across-stages-of-renal-impairment-information-for-primary-care-providers
#10
Lili Tong, Sharon Adler
Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications...
April 18, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29663292/the-potential-role-of-sglt2-inhibitors-in-the-treatment-of-type-1-diabetes-mellitus
#11
Hadi Fattah, Volker Vallon
Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication...
April 16, 2018: Drugs
https://www.readbyqxmd.com/read/29660782/sglt2-inhibitor-induced-changes-in-body-composition-and-simultaneous-changes-in-metabolic-profile-52-week-prospective-light-study-with-luseogliflozin
#12
Takashi Sasaki, Masahiro Sugawara, Masahiro Fukuda
AIMS: It is unclear how changes in body composition induced by sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment correlate with metabolic profile changes. We aimed to clarify how metabolic profile changes correlate with body component changes, and if SGLT2 inhibitor treatment causes sarcopenia and bone mineral content (BMC) loss. MATERIALS AND METHODS: Moderately obese Japanese type 2 diabetes (T2D) patients, treated with luseogliflozin for a year, were observed prospectively and evaluated for body composition changes...
April 16, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29651202/a-narrative-review-of-potential-future-antidiabetic-drugs-should-we-expect-more
#13
REVIEW
Gaurav Chikara, Pramod Kumar Sharma, Pradeep Dwivedi, Jaykaran Charan, Sneha Ambwani, Surjit Singh
Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29649541/efficacy-and-safety-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-type-2-diabetes-and-moderate-renal-function-impairment-a-systematic-review-and-meta-analysis
#14
Lin Zhang, Mei Zhang, Qingguo Lv, Nanwei Tong
AIMS: A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) and moderate renal function impairment. METHODS: Embase, Medline, and Cochrane Central were searched, and randomized controlled trials comparing SGLT2 inhibitors to placebos and other drugs for T2D were collected. RESULTS: Seven RCTs with a total of 3307 participants were included, and the overall bias was low...
April 9, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29627992/beneficial-effect-of-the-sglt2-inhibitor-empagliflozin-on-glucose-homeostasis-and-cardiovascular-parameters-in-the-cohen-rosenthal-diabetic-hypertensive-crdh-rat
#15
Firas Younis, Jonathan Leor, Zaid Abassi, Natalie Landa, Lea Rath, Kenneth Hollander, Nili Naftali-Shani, Talma Rosenthal
The effectiveness of empagliflozin (EMPA), a sodium glucose cotransporter type 2 inhibitor, on the kidney, pancreas, and heart was investigated in the Cohen Rosenthal diabetic hypertensive rat model (CRDH rat). Six-week-old CRDH male rats were fed a sugar diet (SD) and treated with the compound EMPA (group Drug/SD) or respective comparator with vehicle (group Veh/SD). A control group was fed a regular diet without treatment (group Veh/P). Preventive treatment with EMPA was measured during 4 months of follow-up...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29623594/combination-treatment-of-sglt2-inhibitors-and-glp-1-receptor-agonists-symbiotic-effects-on-metabolism-and-cardiorenal-risk
#16
REVIEW
Edison Goncalves, David S H Bell
INTRODUCTION: When treating type 2 diabetes, drugs that cause hypoglycemia and weight gain should, if possible, be avoided. In addition, due to the increased incidence and prevalence of cardiovascular disease, cardiac events and heart failure, as well as the accelerated renal decompensation that may occur with type 2 diabetes, hypoglycemic agents that have the potential to lower cardiac and renal risk should be utilized as early as possible in the course of the disease. METHODS: This is a literature review of the efficacy of combined treatment with a glucagon-like peptide 1 (GLP-1) agonist and a sodium glucose cotransporter-2 (SGLT2) inhibitor in lowering glycated hemoglobin (HbA1c) level, cardiac risk, cardiac events and renal decompensation...
April 5, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29604389/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-cardiovascular-disease-death-and-safety-outcomes-in-type-2-diabetes-a-systematic-review
#17
REVIEW
Karin Rådholm, Jason Hy Wu, Muh Geot Wong, Celine Foote, Gregory Fulcher, Kenneth W Mahaffey, Vlado Perkovic, Bruce Neal
AIM: Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes...
March 28, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29602453/sglt2-inhibitor-induced-euglycaemic-diabetic-ketoacidosis-may-be-due-to-abrupt-severe-and-transient-impaired-glucose-sensing-in-susceptible-individuals-with-a-hitherto-unrecognised-beta-cell-sglt-variant
#18
F M Finucane
Euglycaemic diabetic ketoacidosis (EDKA) is a rare complication of treatment with SGLT2 inhibitors in patients with type 2 diabetes. Uncertainty remains about its precise mechanistic basis, but the physiological derangement is acute and profound, yet reversible with cessation of the drug. It is reminiscent of other "non type 1" presentations with DKA such as ketosis prone diabetes, except that glucose levels are usually normal. Impaired beta cell glucose sensing that mimicked a state of hypoglycaemia could theoretically lead to abrupt and transient cessation of insulin secretion...
May 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29579035/diabetes-and-cardiovascular-disease-from-new-mechanisms-to-new-therapies
#19
Grzegorz Gajos
Diabetes increases the risk of cardiovascular diseases, which are the leading cause of mortality among diabetic patients. Although hyperglycemia is a major determinant of macrovascular and microvascular complications in diabetes, hypoglycemia and glycemic variability have also a strong influence on the cardiovascular system. This overview presents the current state of knowledge on the impact of type 2 diabetes on the cardiovascular system and new therapeutic strategies that have been recently developed to correct gluco-metabolic disturbances in patients with high cardiovascular risk, such as glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors...
March 29, 2018: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29573118/sglt2-inhibitors-and-stroke-risk-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#20
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
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