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https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#1
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
#2
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
#3
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
#4
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
#5
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...
May 18, 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
#6
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
#7
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...
May 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28395363/natural-products-as-lead-compounds-for-sodium-glucose-cotransporter-sglt-inhibitors
#14
Wolfgang Blaschek
Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs)...
April 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28392860/the-effect-of-tofogliflozin-treatment-on-postprandial-glucose-and-lipid-metabolism-in-japanese-men-with-type-2-diabetes-a-pilot-study
#15
Hirokazu Kakuda, Junji Kobayashi, Masaru Sakurai, Masahiro Kakuda, Noboru Takekoshi
BACKGROUND: Postprandial hyperglycemia and hyperlipidemia are highly related to the development of atherosclerosis. Sodium/glucose cotransporter-2 (SGLT2) inhibitors have attracted attention as a new class of anti-diabetic agents for the treatment of type 2 diabetes. We investigated the effect of tofogliflozin on postprandial glucose and lipid metabolism in Japanese male patients with type 2 diabetes. METHODS: Ten Japanese men with type 2 diabetes (average age 66...
May 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#16
M Kim, E J Lee, H M Shin, H S Jung, T K Kim, T N Kim, M J Kwon, S H Lee, B D Rhee, J H Park
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia...
April 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28383832/-cardiovascular-and-renal-protection-of-patients-with-type-2-diabetes-focus-after-empa-reg-outcome-and-leader
#17
REVIEW
A J Scheen, L Piérard, J-M Krzesinski, N Paquot
Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with T2D 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. Both medications showed a significant reduction in major cardiovascular events (-14 and -13 %, respectively), cardiovascular mortality (-38 and -22%), all-cause mortality (-32 and -15 %) and renal events (-39 et -22 %)...
September 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-after-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#18
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well-described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFAs) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance, and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#19
Manisha Garg, Husam Ghanim, Nitesh D Kuhadiya, Kelly Green, Jeanne Hejna, Sanaa Abuaysheh, Barrett Torre, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Paresh Dandona
In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 (SGLT2) inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28303514/euglycemic-ketosis-in-patients-with-type-2-diabetes-on-sglt2-inhibitor-therapy-an-emerging-problem-and-solutions-offered-by-diabetes-technology
#20
A Pfützner, D Klonoff, L Heinemann, N Ejskjaer, J Pickup
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials...
April 2017: Endocrine
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