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Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
December 2016: Journal of Pharmacological Sciences
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
Andrea Egger, Marius E Kraenzlin, Christian Meier
Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk...
December 2016: Current Osteoporosis Reports
Gianluigi Savarese, Carmen D'Amore, Massimo Federici, Fabiana De Martino, Santo Dellegrottaglie, Caterina Marciano, Francesca Ferrazzano, Teresa Losco, Lars H Lund, Bruno Trimarco, Giuseppe M C Rosano, Pasquale Perrone-Filardi
BACKGROUND: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis. METHODS: Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included...
October 1, 2016: International Journal of Cardiology
R W Coch, J B Green
AIMS: The increased risk of cardiovascular disease in patients with type 2 diabetes has been known for many years. However, until recently the cardiovascular (CV) impact of glucose lowering strategies has been inadequately understood. Major clinical trials have now investigated the impact of intensification of glycemic control upon CV outcomes, as well as the CV effects of glucose management with newer antihyperglycemic agents. DATA SYNTHESIS: Key findings from recently completed CV outcomes trials of dipeptidyl peptidase-4 (DPP4) inhibitors, GLP-1 receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors completed thus far are reviewed and summarized...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
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 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...
January 2017: Diabetes/metabolism Research and Reviews
Teresa Vanessa Fiorentino, Giorgio Sesti
Clinical trials of glucose-lowering strategies in patients with type 2 diabetes mellitus (T2DM) have shown a favorable effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular events. In 2008, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have required stringent criteria to approve new glucose-lowering drugs, demanding proof of cardiovascular safety. As a result of these regulatory requirements, a number of cardiovascular outcome trials in T2DM have been conducted examining the cardiovascular safety of novel glucose-lowering drugs...
March 2016: Giornale Italiano di Cardiologia
Brian Tomlinson, Miao Hu, Yuzhen Zhang, Paul Chan, Zhong-Min Liu
INTRODUCTION: The increasing prevalence of type 2 diabetes mellitus (T2DM) and the eventual need for multiple medications in most patients stimulated the development of new drug classes to reduce plasma glucose levels. The GLP-1 receptor agonists (GLP-1RAs) are established as an option for treatment of T2DM after metformin. They are also effective in reducing body weight but current GLP-1RAs have to be given by subcutaneous injection daily or once weekly. AREAS COVERED: This review focuses on the new GLP-1RAs currently undergoing development, some of which require less frequent subcutaneous administration and others that are being developed in oral formulations that may favor patient adherence...
2016: Expert Opinion on Investigational Drugs
Janet B McGill
No abstract text is available yet for this article.
September 2015: Endocrine Practice
Bernard E Tuch
Type 2 diabetes is a growing problem, with 387 million people currently affected, and 592 million by 2035. Whilst diet and exercise are the corner stones of treatment, oral hypoglycaemic agents are often needed to achieve glycaemic control, thereby reducing the chance of long term diabetic complications. Biguanides and sulfonylureas have been the standard tablets used for this disorder, until 2005-7 when glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors became available. Their major advantage over sulfonylureas is that they are weight lowering or weight neutral, and have a very low incidence of hypoglycaemia...
January 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Takahiro Oguma, Keiko Nakayama, Chiaki Kuriyama, Yasuaki Matsushita, Kumiko Yoshida, Kumiko Hikida, Naoyuki Obokata, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masaharu Shiotani
The sodium glucose cotransporter (SGLT) 1 plays a major role in glucose absorption and incretin hormone release in the gastrointestinal tract; however, the impact of SGLT1 inhibition on plasma glucagon-like peptide-1 (GLP-1) levels in vivo is controversial. We analyzed the effects of SGLT1 inhibitors on GLP-1 secretion in normoglycemic and hyperglycemic rodents using phloridzin, CGMI [3-(4-cyclopropylphenylmethyl)-1-(β-d-glucopyranosyl)-4-methylindole], and canagliflozin. These compounds are SGLT2 inhibitors with moderate SGLT1 inhibitory activity, and their IC50 values against rat SGLT1 and mouse SGLT1 were 609 and 760 nM for phloridzin, 39...
September 2015: Journal of Pharmacology and Experimental Therapeutics
Ele Ferrannini, Ralph A DeFronzo
Type 2 diabetes mellitus (T2DM) is characterized by multiple pathophysiologic abnormalities. With time, multiple glucose-lowering medications are commonly required to reduce and maintain plasma glucose concentrations within the normal range. Type 2 diabetes mellitus individuals also are at a very high risk for microvascular complications and the incidence of heart attack and stroke is increased two- to three-fold compared with non-diabetic individuals. Therefore, when selecting medications to normalize glucose levels in T2DM patients, it is important that the agent not aggravate, and ideally even improve, cardiovascular risk factors (CVRFs) and reduce cardiovascular morbidity and mortality...
September 7, 2015: European Heart Journal
Pendar Farahani
PURPOSE: Pharmacotherapy for diabetes in real-world clinical settings is very complex and is posing a challenge for residents in training. The purpose of this study was to explore the views of residents in Canada regarding educational priorities for pharmacotherapy in diabetes management. METHODS: A questionnaire was developed to explore different domains of pharmacotherapy in diabetes management, including different clinic>al settings, combination pharmacotherapy with different classes of medications and patients' characteristics, including comorbidities and cardiovascular risk factors...
May 31, 2015: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
Christian Meier, Ann V Schwartz, Andrea Egger, Beata Lecka-Czernik
Type 2 diabetes is associated with increased fracture risk and the mechanisms underlying the detrimental effects of diabetes on skeletal health are only partially understood. Antidiabetic drugs are indispensable for glycemic control in most type 2 diabetics, however, they may, at least in part, modulate fracture risk in exposed patients. Preclinical and clinical data clearly demonstrate an unfavorable effect of thiazolidinediones on the skeleton with impaired osteoblast function and activated osteoclastogenesis...
January 2016: Bone
Jan Šoupal, Martin Prázný
SGLT2 and DPP4 inhibitors are new effective oral antidiabetic drugs with low risk of hypoglycemia and positive or neutral impact on body weight. These characteristics are substantially different from more widely used sulphonyl-ureas. Current treatment of type 2 diabetes is rather complicated. Moreover, the position of new antidabetics in the guidelines has not yet been clearly defined. Personalised treatment on the basis of molecular markers is still not possible. Therefore, the position of new antidiabetics in the treatment of type 2 diabetes is often determined by clinical experience and subsequently modified by new clinical studies...
April 2015: Vnitr̆ní Lékar̆ství
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Yoshida, Satoko Kiuchi, Yuka Ikenaga, Yoshinobu Nakamaru, Kumiko Hikida, Akira Saito, Kenji Arakawa, Kozo Oka, Kiichiro Ueta, Masaharu Shiotani
To assess the impact of concomitant inhibition of sodium-glucose cotransporter (SGLT) 2 and dipeptidyl peptidase IV (DPP4) for the treatment of type 2 diabetes mellitus (T2DM), the effect of combined treatment with canagliflozin, a novel SGLT2 inhibitor, and teneligliptin, a DPP4 inhibitor, on glucose intolerance was investigated in Zucker diabetic fatty (ZDF) rats. Canagliflozin potently inhibited human and rat SGLT2 and moderately inhibited human and rat SGLT1 activities but did not affect DPP4 activity. In contrast, teneligliptin inhibited human and rat DPP4 activities but not SGLT activities...
April 2015: Journal of Pharmacological Sciences
Friedrich Mittermayer, Erica Caveney, Claudia De Oliveira, Loukas Gourgiotis, Mala Puri, Li-Jung Tai, J Rick Turner
The global burden of type 2 diabetes is increasing worldwide, and successful treatment of this disease needs constant provision of new drugs. Twelve classes of antidiabetic drugs are currently available, and many new drugs are under clinical development. These include compounds with known mechanisms of action but unique properties, such as once-weekly DPP4 inhibitors or oral insulin. They also include drugs with new mechanisms of action, the focus of this review. Most of these compounds are in Phase 1 and 2, with only a small number having made it to Phase 3 at this time...
2015: Current Diabetes Reviews
André J Scheen
No abstract text is available yet for this article.
November 2013: Lancet Diabetes & Endocrinology
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