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Sglt2 receptors

Soo Lim, Robert H Eckel, Kwang Kon Koh
The final goal in the management of patients with type 2 diabetes (T2D) is reduction in cardiovascular (CV) complications and total mortality. Various factors including hyperglycemia contribute to these complications and mortality directly and indirectly. In recent years, large-scale CV outcome trials with new antidiabetic medications, such as dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and sodium glucose cotransporter-2 (SGLT2) inhibitors, have been completed...
March 8, 2018: Atherosclerosis
Carol H Wysham, Dominic Pilon, Mike Ingham, Marie-Hélène Lafeuille, Bruno Emond, Rhiannon Kamstra, Michael Pfeifer, Patrick Lefebvre
OBJECTIVE: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012-April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics...
March 2018: Endocrine Practice
Milton Packer, Dalane W Kitzman
Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired...
March 7, 2018: JACC. Heart Failure
Petar M Seferović, Mark C Petrie, Gerasimos S Filippatos, Stefan D Anker, Giuseppe Rosano, Johann Bauersachs, Walter J Paulus, Michel Komajda, Francesco Cosentino, Rudolf A de Boer, Dimitrios Farmakis, Wolfram Doehner, Ekaterini Lambrinou, Yuri Lopatin, Massimo F Piepoli, Michael J Theodorakis, Henrik Wiggers, John Lekakis, Alexandre Mebazaa, Mamas A Mamas, Carsten Tschöpe, Arno W Hoes, Jelena P Seferović, Jennifer Logue, Theresa McDonagh, Jillian P Riley, Ivan Milinković, Marija Polovina, Dirk J van Veldhuisen, Mitja Lainscak, Aldo P Maggioni, Frank Ruschitzka, John J V McMurray
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice...
March 8, 2018: European Journal of Heart Failure
Annas Al-Sharea, Andrew J Murphy, L A Huggins, Y Hu, Ira J Goldberg, Prabhakara R Nagareddy
BACKGROUND AND AIMS: Leukocytosis, particularly monocytosis, has been shown to promote atherosclerosis in both diabetic and non-diabetic mouse models. We previously showed that hyperglycemia independently promotes monocytosis and impairs the resolution of atherosclerosis. Since patients with chronic diabetes often develop dyslipidemia and also have increased risk for atherosclerosis, we sought to examine how controlling blood glucose affects atherosclerosis development in the presence of severe hyperlipidemia...
March 2, 2018: Atherosclerosis
Bernhard Ludvik, Juan P Frías, Francisco J Tinahones, Julio Wainstein, Honghua Jiang, Kenneth E Robertson, Luis-Emilio García-Pérez, D Bradley Woodward, Zvonko Milicevic
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. METHODS: AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA...
February 23, 2018: Lancet Diabetes & Endocrinology
Christophe De Block
No abstract text is available yet for this article.
February 23, 2018: Lancet Diabetes & Endocrinology
Shin-Ichi Harashima, Nobuya Inagaki, Kazuoki Kondo, Nobuko Maruyama, Makiko Otsuka, Yutaka Kawaguchi, Yumi Watanabe
Sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are antihyperglycaemic agents with weight-lowering effects. The efficacy and safety of the SGLT2 inhibitor canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control with a GLP-1RA (≥12 weeks) were evaluated in this phase IV study. Patients received canagliflozin 100 mg once daily for 52 weeks. Efficacy endpoints included the change in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), bodyweight, systolic blood pressure (SBP), and high-density lipoprotein cholesterol (HDL-C) from baseline to Week 52...
February 23, 2018: Diabetes, Obesity & Metabolism
Eva Toft, Mikael Rydén
Do novel therapies in type 2 diabetes have protective effects on cardiovascular and renal complications? A number of new antidiabetic drug classes have been introduced on the market in the last decade. Regulatory authorities have required that their safety in type 2 diabetes populations with high cardiovascular risk must be assessed. Consequently, a large number of outcome studies have been initiated, several of which have been published in recent years. Overall, this has so far shown that long-acting insulin analogues, DPP4-inhibitors, GLP1-receptor agonists and SGLT2-inhibitors are safe...
February 20, 2018: Läkartidningen
Tatsuhiko Urakami
The principal treatment for children and adolescents with type 2 diabetes is dietary and exercise management. However, the blood glucose levels of some patients receiving this treatment fail to improve; thus, pharmacological treatment is eventually required. The pathophysiology of type 2 diabetes in pediatric patients appears to be similar to that in adults; thus, the range of antidiabetic drugs used in adults is likely to be effective in pediatric patients as well. However, in the majority of countries, including Japan, only metformin, glimepiride, and insulin have been approved for use in pediatric patients...
2018: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
Shigehiro Katayama, Masako Hatano, Masashi Issiki
Over 50% of patients with diabetes mellitus, either type 1 or 2, ultimately develop hypertension as a complication. In diabetics, this further increases the incidence of cardiovascular disease (CVD) by 2- to 3-fold and accelerates the progression of diabetic nephropathy. Arteriosclerosis, a clinical feature of hypertension in diabetics, develops and advances from a young age. Therefore, in providing treatment, it is necessary to evaluate the degree of arteriosclerosis. Diabetic patients are encouraged to strictly control their blood glucose levels...
February 5, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Kumiko Shiba, Kyoichiro Tsuchiya, Chikara Komiya, Yasutaka Miyachi, Kentaro Mori, Noriko Shimazu, Shinobu Yamaguchi, Naomi Ogasawara, Makoto Katoh, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa
Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes...
February 5, 2018: Scientific Reports
A J Scheen, N Paquot
Two classes of antidiabetic agents have shown a cardiovascular and renal protection in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, and liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, were granted a reduction of major cardiovascular events and mortality after the positive results of EMPA-REG OUTCOME and LEADER outcome trials, respectively. Protection mechanisms most probably differ between the two pharmacological classes and are perhaps complementary...
January 2018: Revue Médicale de Liège
Michael Nassif, Mikhail Kosiborod
Heart failure is one of the most common comorbidities of diabetes mellitus. Glucose-lowering therapies that can prevent heart failure or improve outcomes in patients with established heart failure are of critical importance among those with type 2 diabetes. Several types of glucose-lowering drugs have been assessed in this setting. Metformin has been shown to modestly improve the outcomes of patients with heart failure, whereas the effect of insulin in those with established heart failure is less clear. The effect of sulfonylureas on improving heart failure is controversial; observational reports have suggested that they are harmful in these patients, but these data have not been confirmed in randomized, controlled trials...
January 25, 2018: Nature Reviews. Cardiology
Alberto Palazzuoli, Elena Ceccarelli, Gaetano Ruocco, Ranuccio Nuti
Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate...
January 23, 2018: Heart Failure Reviews
Samy Suissa
Two recent large-scale cardiovascular outcome trials, a now common tool in assessing the safety of pharmacological treatments for type 2 diabetes, reported significant reductions in all-cause mortality. In EMPA-REG OUTCOME [BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients], patients who received the SGLT2 inhibitor empagliflozin had a notable reduction of 9.2 deaths per 1,000 per year, while LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation) found that the patients receiving the GLP-1 receptor agonist liraglutide had a reduction of 3...
February 2018: Diabetes Care
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
Yukio Horikawa, Mayumi Enya, Makie Komagata, Ken-Ichi Hashimoto, Masayo Kagami, Maki Fukami, Jun Takeda
INTRODUCTION: Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. CASE REPORT: A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents...
February 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
March 2018: Expert Opinion on Drug Safety
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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