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Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
Bhavana Sosale, Aravind R Sosale, Prassanna M Kumar, Shashank R Joshi
BACKGROUND AND AIM: The number of patients with type 2 diabetes (T2DM) is increasing. Most patients with T2DM are uncontrolled and fail to achieve their target Hba1c. In recent years, newer agents such as SGLT2 inhibitors (SGLT2i) have been approved for clinical use. Though data from clinical trials and sub set analysis of Indian patients in global studies are promising, real world evidence from standard clinical practice in India is lacking. The aim of this study was to analyze the metabolic parameters in patients with T2DM on SGLT2i in real world clinical practice...
September 2016: Journal of the Association of Physicians of India
Fumitaka Okajima, Tomoko Nagamine, Yuko Nakamura, Naomi Hattori, Hitoshi Sugihara, Naoya Emoto
The efficacy of the administration of sodium-glucose co-transporter 2 inhibitor (SGLT2I) or the co-administration of SGLT2I and dipeptidyl peptidase-4 inhibitor (DPP-4I) to insulin therapy is not well known. Fifty-eight patients with type 2 diabetes, admitted for glycemic control, were randomized to basal-bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring (CGM) before discharge...
October 20, 2016: Journal of Diabetes Investigation
Hitesh Soni
Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral...
October 2016: Medical Hypotheses
Giuseppe Daniele, Juan Xiong, Carolina Solis-Herrera, Aurora Merovci, Roy Eldor, Devjit Tripathy, Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
OBJECTIVE: Insulin resistance is associated with mitochondrial dysfunction and decreased ATP synthesis. Treatment of individuals with type 2 diabetes mellitus (T2DM) with sodium-glucose transporter 2 inhibitors (SGLT2i) improves insulin sensitivity. However, recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i. The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1) mitochondrial ATP synthesis and 2) substrate oxidation rates and ketone production...
August 25, 2016: Diabetes Care
Matteo Monami, Ilaria Dicembrini, Edoardo Mannucci
AIMS: EMPAREG OUTCOME study showed a reduction in cardiovascular events in patients treated with the sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin, as compared to placebo. Other drugs of the same class are currently been investigated for cardiovascular outcomes. In the meanwhile, a re-analysis of data collected in available studies can add relevant insight. METHODS: A MEDLINE search for SGLT-2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials up to November 16, 2015...
August 4, 2016: Acta Diabetologica
John P H Wilding, Surya Panicker Rajeev, Ralph A DeFronzo
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin)...
August 2016: Diabetes Care
André J Scheen
INTRODUCTION: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. AREA COVERED: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations...
July 29, 2016: Expert Opinion on Drug Metabolism & Toxicology
Sanjay Kalra, Vikram Singh, Dinesh Nagrale
UNLABELLED: Blood glucose-lowering treatment options generally target insulin action or beta-cell function. In diabetes, expression of the sodium-glucose cotransporter-2 (SGLT2) genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening the hyperglycemic condition. The SGLT2 inhibitors (SGLT2i) are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion...
September 2016: Advances in Therapy
Kuralay Atageldiyeva, Yukihiro Fujita, Tsuyoshi Yanagimachi, Katsutoshi Mizumoto, Yasutaka Takeda, Jun Honjo, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Masakazu Haneda
A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin...
2016: PloS One
Se Hee Min, Jeong-Hwa Yoon, Seokyung Hahn, Young Min Cho
BACKGROUND: Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors. METHODS: We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, and through June 2015. Randomized controlled trials (RCTs) published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected...
May 7, 2016: Diabetes/metabolism Research and Reviews
Yumiko Chiba, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Yoichiro Asai, Takashi Sugisawa, Kenji Uno, Shojiro Sawada, Junta Imai, Kazuhiro Nakamura, Hideki Katagiri
Selective sodium glucose cotransporter-2 inhibitor (SGLT2i) treatment promotes urinary glucose excretion, thereby reducing blood glucose as well as body weight. However, only limited body weight reductions are achieved with SGLT2i treatment. Hyperphagia is reportedly one of the causes of this limited weight loss. However, the effects of SGLT2i treatment on systemic energy expenditure have not been fully elucidated. Herein, we investigated the acute effects of dapagliflozin, a SGLT2i, on systemic energy expenditure in mice...
2016: PloS One
Yasushi Honda, Kento Imajo, Takayuki Kato, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Shingo Kato, Hironori Mawatari, Koji Fujita, Masato Yoneda, Satoru Saito, Atsushi Nakajima
BACKGROUND & AIMS: In recent years, nonalcoholic steatohepatitis (NASH) has become a considerable healthcare burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus (T2DM) and insulin resistance. However, a specific drug to treat NASH is lacking. We investigated the effect of the selective sodium glucose cotransporter 2 inhibitor (SGLT2I) ipragliflozin on NASH in mice. METHODS: We used the Amylin liver NASH model (AMLN), which is a diet-induced model of NASH that results in obesity and T2DM...
2016: PloS One
Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Masaharu Nagashima, Hideki Kushima, Takuya Watanabe, Tsutomu Hirano
Direct associations between hyperglycemia and atherosclerosis remain unclear. We investigated the association between the amelioration of glycemia by sodium-glucose cotransporter 2 inhibitors (SGLT2is) and macrophage-driven atherosclerosis in diabetic mice. We administered dapagliflozin or ipragliflozin (1.0 mg/kg/day) for 4-weeks to apolipoprotein E-null (Apoe-/-) mice, streptozotocin-induced diabetic Apoe-/- mice, and diabetic db/db mice. We then determined aortic atherosclerosis, oxidized low-density lipoprotein (LDL)-induced foam cell formation, and related gene expression in exudate peritoneal macrophages...
2015: PloS One
Awadhesh Kumar Singh, Ritu Singh
No single antidiabetic agent can correct all the pathophysiologic defects manifested in type 2 diabetes mellitus (T2DM) and, therefore, multiple agents are often required to achieve optimal glycemic control. Combination therapies, having different mechanisms of action, not only have the potential to complement their action, but may possess the properties to counter the undesired compensatory response. Recent finding suggests that sodium-glucose co-transporter-2 inhibitors (SGLT2i) increase endogenous glucose production (EGP) from liver, due to the increase in glucagon which may offset its glucose-lowering potential...
2016: Expert Review of Clinical Pharmacology
C Triplitt, C Solis-Herrera, E Cersosimo, M Abdul-Ghani, Ralph A Defronzo
INTRODUCTION: Many patients with type 2 diabetes mellitus (T2DM) fail to achieve the desired A1c goal because the antidiabetic medications used do not correct the underlying pathophysiologic abnormalities and monotherapy is not sufficiently potent to reduce the A1c to the 6.5 - 7.0% range. Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in T2DM. We examine combination therapy with linagliptin plus empagliflozin as a therapeutic approach for the treatment of inadequately controlled T2DM patients...
2015: Expert Opinion on Pharmacotherapy
J Yoon, S H Min, S Hahn, Y M Cho
No abstract text is available yet for this article.
November 2015: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Heidi Storgaard, Jonatan I Bagger, Filip K Knop, Tina Vilsbøll, Jørgen Rungby
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have been suggested to predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis (DKA) developed in an obese, poorly controlled male patient with T2D treated with the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of treatment with the SGLT2i dapagliflozin...
February 2016: Basic & Clinical Pharmacology & Toxicology
Daisuke Yabe, Rie Nishikino, Makiko Kaneko, Masahiro Iwasaki, Yutaka Seino
Sodium/glucose co-transporter 2 inhibitors (SGLT2i) represent a novel class of glucose-lowering agents that lower plasma glucose levels through pharmacological inhibition of glucose reuptake from the kidney, independent of insulin secretion and action. Clinical trials of SGLT2i demonstrated therapeutic benefits on glycemic control and bodyweight in individuals with type 2 diabetes, with few cases of serious adverse events (SAEs). However, a considerable number of SAEs were reported in patients receiving SGLT2i clinically in Japan during the first 3 months of their use...
June 2015: Expert Opinion on Drug Safety
Matthias Oelze, Swenja Kröller-Schön, Philipp Welschof, Thomas Jansen, Michael Hausding, Yuliya Mikhed, Paul Stamm, Michael Mader, Elena Zinßius, Saule Agdauletova, Anna Gottschlich, Sebastian Steven, Eberhard Schulz, Serge P Bottari, Eric Mayoux, Thomas Münzel, Andreas Daiber
OBJECTIVE: In diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress...
2014: PloS One
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