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https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#1
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28761216/use-of-canagliflozin-in-combination-with-and-compared-to-incretin-based-therapies-in-type-2-diabetes
#2
Richard E Pratley, Eugenio Cersosimo
In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1 [GLP-1] receptor agonists) are widely used to treat patients with type 2 diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor, has demonstrated superior A1C lowering compared to the DPP-4 inhibitor sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood pressure reduction. The addition of canagliflozin to treatment regimens that include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further improve glycemic control, while still maintaining beneficial effects on cardiometabolic parameters such as body weight and blood pressure...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28743778/fracture-risk-associated-with-common-medications-used-in-treating-type-2-diabetes-mellitus
#3
Daniel Wolverton, Melissa M Blair
PURPOSE: Published data on the risk of bone fractures associated with medications used for the treatment of type 2 diabetes mellitus are summarized. SUMMARY: A systematic literature search identified 108 publications on controlled trials and 6 meta-analyses addressing the potential for fractures with the use of 7 commonly used antidiabetic classes: thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, biguanides, insulin, and sulfonylureas...
August 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28683796/effectiveness-of-dapagliflozin-on-vascular-endothelial-function-and-glycemic-control-in-patients-with-early-stage-type-2-diabetes-mellitus-defence-study
#4
Fumika Shigiyama, Naoki Kumashiro, Masahiko Miyagi, Kayoko Ikehara, Eiichiro Kanda, Hiroshi Uchino, Takahisa Hirose
BACKGROUND: Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM...
July 6, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28675686/the-challenges-of-achieving-postprandial-glucose-control-using-closed-loop-systems-in-patients-with-type-1-diabetes
#5
REVIEW
Véronique Gingras, Nadine Taleb, Amélie Roy-Fleming, Laurent Legault, Rémi Rabasa-Lhoret
For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared to conventional therapy. Yet, reducing glucose excursion as well as simplification of prandial insulin doses remains a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes...
July 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28671791/-cardiovascular-protection-of-patients-with-type-2-diabetes-from-empa-reg-outcome-to-leader
#6
André J Scheen, Caroline Wallemacq, Bernard Jandrain, Philippe Ernest
Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively)...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28657399/combination-sglt2-inhibitor-and-glp-1-receptor-agonist-therapy-a-complementary-approach-to-the-treatment-of-type-2-diabetes
#7
Robert S Busch, Michael P Kane
Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia...
June 28, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#8
Claire Ritz, Jaafar Jaafar, Jacques Philippe
Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#9
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28601988/surgical-and-advanced-medical-therapy-for-the-treatment-of-type-2-diabetes-in-class-i-obese-patients-a-short-term-outcome
#10
Mohit Bhandari, Winni Mathur, Ravindra Kumar, Arun Mishra, Mahak Bhandari
BACKGROUND: Bariatric surgery, incretin-based therapy (glucagon-like peptide-1 analogues), and sodium-glucose co-transporter 2 (SGLT2) inhibitors have antidiabetic properties in morbidly obese patients. However, their comparative efficacy in treating type 2 diabetes mellitus (T2DM) in class I obese patients specifically in Indian has not been studied yet. This study evaluates and compares the efficacy and side effect of surgical and advanced medical management of T2DM in class I obese patients...
June 11, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28584109/dapagliflozin-suppresses-glucagon-signaling-in-rodent-models-of-diabetes
#11
May-Yun Wang, Xinxin Yu, Young Lee, Sara Kay McCorkle, Shiuhwei Chen, Jianping Li, Zhao V Wang, Jaime A Davidson, Philipp E Scherer, William L Holland, Roger H Unger, Michael G Roth
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28570924/effects-of-sglt-2-inhibitors-on-diabetic-ketoacidosis-a-meta-analysis-of-randomised-controlled-trials
#12
Matteo Monami, Besmir Nreu, Stefania Zannoni, Carlotta Lualdi, Edoardo Mannucci
AIMS: Diabetic ketoacidosis (DKA) associated with SGLT-2 inhibitors (SGLT-2i) is a possible adverse event. In fact, SGLT-2i are capable of stimulating the release of glucagon and ketone re-absorption in the renal tubuli, thus increasing the concentration of ketone bodies. METHODS: A Medline search for SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials with a duration of treatment≥12weeks, enrolling patients with type 2 diabetes, and comparing a SGLT2i with placebo or other comparators...
August 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#13
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/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#14
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...
July 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
#15
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/28499695/dapagliflozin-modulates-glucagon-secretion-in-an-sglt2-independent-manner-in-murine-alpha-cells
#16
A Solini, G Sebastiani, L Nigi, E Santini, C Rossi, F Dotta
AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28472182/common-variation-in-the-sodium-glucose-cotransporter-2-gene-slc5a2-does-neither-affect-fasting-nor-glucose-suppressed-plasma-glucagon-concentrations
#17
Anna-Maria Ordelheide, Anja Böhm, Daniela Kempe-Teufel, Robert Wagner, Fausto Machicao, Martin Heni, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
AIM: Inhibition of sodium/glucose cotransporter 2 (SGLT2), the key transport protein in renal glucose reabsorption, promotes glucose excretion and represents a new concept in the therapy of type-2 diabetes. In addition, SGLT2 inhibition elevates circulating glucagon concentrations and enhances hepatic glucose production. Since SGLT2 is expressed in human pancreatic α-cells and regulates glucagon release, we tested whether common variants of the SGLT2 gene SLC5A2 associate with altered plasma glucagon concentrations in the fasting state and upon glucose challenge...
2017: PloS One
https://www.readbyqxmd.com/read/28432726/combination-therapy-with-glp-1-receptor-agonist-and-sglt2-inhibitor
#18
REVIEW
Ralph A DeFronzo
The SGLT2 inhibitors (SGLTi) and glucagon-like-1 receptor agonists (GLP-1 RAs) effectively reduce HbA1c, but via very different mechanisms, making them an effective duet for combination therapy. Recently, drugs in both of these antidiabetic classes have been shown to reduce cardiovascular events, most probably by different mechanisms. SGLT2i appear to exert their CV protective actions by haemodynamic effects, while GLP-1 RAs work via anti-atherogenic/anti-inflammatory mechanisms, raising the possibility that combined therapy with these 2 classes may produce additive CV benefits...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#19
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#20
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
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