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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/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#2
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28801475/understanding-the-gap-between-efficacy-in-randomized-controlled-trials-and-effectiveness-in-real-world-use-of-glp-1ra-and-dpp4-therapies-in-patients-with-type-2-diabetes
#3
Ginger S Carls, Edward Tuttle, Ruo-Ding Tan, Johnny Huynh, John Yee, Steven V Edelman, William H Polonsky
OBJECTIVE: This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs...
August 11, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28764219/teneligliptin-in-early-diabetic-kidney-disease-an-observation-in-asian-indian-patients-with-type-2-diabetes-mellitus-in-real-life-scenario
#4
Kiran Shah
INTRODUCTION: Teneligliptin is a recently developed Dipeptidyl Peptidase 4 (DPP4) inhibitor. Teneligliptin is suitable for glycaemic control with renal impairment including end stage renal disease. AIM: To assess the efficacy and safety of teneligliptin in Asian Indian patients of Type 2 Diabetes Mellitus (T2DM) with early Diabetic Kidney Disease (DKD). MATERIALS AND METHODS: This was a single centre, retrospective analysis of patients with early DKD, who received teneligliptin 20 mg once daily for 24 weeks...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28756774/heart-failure-hospitalization-risk-associated-with-use-of-two-classes-of-oral-antidiabetic-medications-an-observational-real-world-analysis
#5
Santosh Gautam, Abiy Agiro, John Barron, Thomas Power, Harry Weisman, Jeff White
BACKGROUND: Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium-glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients. METHODS: This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included...
July 31, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28750074/dpp4-gene-variation-affects-glp-1-secretion-insulin-secretion-and-glucose-tolerance-in-humans-with-high-body-adiposity
#6
Anja Böhm, Robert Wagner, Fausto Machicao, Jens Juul Holst, Baptist Gallwitz, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF)...
2017: PloS One
https://www.readbyqxmd.com/read/28747063/dpp4-inhibitors-can-be-a-drug-of-choice-for-type-3-diabetes-a-mini-review
#7
Nehru Sai Suresh Chalichem, Chaitanya Gonugunta, Praveen Thaggikuppe Krishnamurthy, Basavan Duraiswamy
As well known to the scientific community, Alzheimer's disease (AD) is an irreversible neurodegenerative disease that ends up with impairment of memory and cognition due to neuronal and synapse loss. Patient's quality of life can be enhanced by targeting neurogenesis as a therapeutic paradigm. Moreover, several research evidences support the concept that AD is a type of metabolic disorder mediated by impairment in brain insulin responsiveness and energy metabolism. Growing evidence suggests that endogenous peptides such as glucagon-like peptide-1 (GLP-1) and stromal-derived factor-1α (SDF-1α) provide neuroprotection across a range of experimental models of AD...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28736981/ketoacidosis-and-sglt2-inhibitor-treatment-analysis-of-faers-data
#8
Jenny E Blau, Sri Harsha Tella, Simeon I Taylor, Kristina I Rother
BACKGROUND: Regulatory agencies have concluded that sodium glucose cotransporter 2 (SGLT2) inhibitors lead to ketoacidosis, but published literature on this point remains controversial. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) for reports of acidosis in patients treated with canagliflozin, dapagliflozin, or empagliflozin (from the date of each drug's FDA approval until May 15, 2015). We compared the number of SGLT2 inhibitor-related reports to reports of acidosis in patients treated with the two most commonly used DPP4 inhibitors: sitagliptin and saxagliptin...
July 24, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#9
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#10
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28680862/sglt2-inhibitors-as-add-on-therapy-in-type-2-diabetes-a-real-world-study
#11
Héctor Eloy Tamez-Perez, Enrique Delgadillo-Esteban, David Soni-Duque, Mayra Ivonne Hernández-Coria, Alejandra Lorena Tamez-Peña
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive chronic disease associated with severe microvascular and macrovascular complications. Our aim is to assess the real world effectiveness of SGT" inhibitors in achieving metabolic therapeutic goals. METHODS: A retrospective, observational study. Inclusion criteria for patients were a previous diagnosis of type 2 diabetes mellitus, age > 18 years, patients receiving either dapagliflozin 10 mg and/or canagliflozin 300 mg...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28659588/the-dual-dpp4-inhibitor-and-gpr119-agonist-hbk001-regulates-glycemic-control-and-beta-cell-function-ex-and-in-vivo
#12
Yi Huan, Qian Jiang, Gang Li, Guoliang Bai, Tian Zhou, Shuainan Liu, Caina Li, Quan Liu, Sujuan Sun, Miaomiao Yang, Nan Guo, Xing Wang, Shusen Wang, Yaojuan Liu, Guanqiao Wang, Haihong Huang, Zhufang Shen
Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining β-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630069/degradation-of-incretins-and-modulation-of-blood-glucose-levels-by-periodontopathic-bacterial-dipeptidyl-peptidase-4
#13
Yuko Ohara-Nemoto, Manami Nakasato, Yu Shimoyama, Tomomi T Baba, Takeshi Kobayakawa, Toshio Ono, Takashi Yaegashi, Shigenobu Kimura, Takayuki K Nemoto
Severe periodontitis is known to aggravate diabetes mellitus, though molecular events related to that link have not been fully elucidated. Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans. We examined the enzymatic characteristics of DPP4 from P. gingivalis as well as two other periodontopathic bacteria, Tannerella forsythia and Prevotella intermedia, and determined whether it is capable of regulating blood glucose levels...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28585374/svmdlf-a-novel-r-based-web-application-for-prediction-of-dipeptidyl-peptidase-4-inhibitors
#14
Sharat Chandra, Jyotsana Pandey, Akhilesh K Tamrakar, Mohammad Imran Siddiqi
Dipeptidyl peptidase 4 (DPP4) is a well-known target for the antidiabetic drugs. However, currently available DPP4 inhibitor screening assays are costly and labor-intensive. It is important to create a robust in-silico method to predict the activity of DPP4 inhibitor for the new lead finding. Here, we introduce a R based web application SVMDLF (SVM based DPP4 Lead Finder) to predict the inhibitor of DPP4; based on support vector machine (SVM) model, predictions of which are confirmed by in-vitro biological evaluation...
June 6, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28575350/dipeptidyl-peptidase-iv-as-a-prognostic-marker-and-therapeutic-target-in-papillary-thyroid-carcinoma
#15
Jie-Jen Lee, Tao-Yeuan Wang, Chien-Liang Liu, Ming-Nan Chien, Ming-Jen Chen, Yi-Chiung Hsu, Ching-Hsiang Leung, Shih-Ping Cheng
Context: Dipeptidyl peptidase IV (DPP4) is overexpressed in thyroid cancer and certain malignancies. Furthermore, DPP4 has been identified as a discriminatory marker for thyroid cancer. However, it remains unclear whether DPP4 expression plays a prognostic role. Objective: The aim of this study was to investigate the expression and function of DPP4 in thyroid cancer and the mechanisms involved. Design: We determined the expression of DPP4 by immunohistochemistry in tissue microarrays of thyroid tumors...
May 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28542373/comparative-effectiveness-of-oral-antidiabetic-drugs-in-preventing-cardiovascular-mortality-and-morbidity-a-network-meta-analysis
#16
Gyeongsil Lee, Seung-Won Oh, Seung-Sik Hwang, Ji Won Yoon, Sungchan Kang, Hee-Kyung Joh, Hyuktae Kwon, Jeehyun Kim, Danbee Park
In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28539088/prescription-patterns-and-disease-control-in-type-2-diabetes-mellitus-patients-in-nursing-home-and-home-care-settings-a-retrospective-analysis-in-germany
#17
Karel Kostev, Timo Rockel, Louis Jacob
AIM: The aim of this study was to analyze prescription patterns and disease control in patients with type 2 diabetes mellitus (T2DM) in nursing home and home care settings in Germany. METHODS: The present study is based on data from the Disease Analyzer database (QuintilesIMS). Patients with an initial diagnosis of T2DM and documented HbA1c values between January 2011 and December 2015 were included in the analysis. The index date corresponded to the last documented HbA1c value...
May 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28534682/diabetic-ketoacidosis-a-common-debut-of-diabetes-among-african-americans-with-type-2-diabetes
#18
Priyathama Vellanki, Guillermo E Umpierrez
OBJECTIVE: More than half of African Americans (AA) with a new diagnosis of diabetic ketoacidosis have clinical and metabolic features of type 2 diabetes during follow-up. This particular presentation of diabetes has been termed as ketosis-prone type 2 diabetes (KPDM) or atypical diabetes. METHODS: We review the epidemiology, diagnosis, pathophysiology, and acute and long-term management of AA with KPDM and compare these similarities to patients with type 2 diabetes...
August 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28514822/-cardiovascular-effects-of-antidiabetic-therapies
#19
Katharina Laubner, Jochen Seufert
Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin...
May 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28502212/-trends-in-antidiabetic-treatment-prescribed-for-patients-with-type-2-diabetes-in-hungary-between-2001-and-2014-results-from-the-database-analysis-of-the-national-health-insurance-fund
#20
György Jermendy, Zoltán Kiss, György Rokszin, Zsolt Abonyi-Tóth, István Wittmann, Péter Kempler
In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000...
May 2017: Orvosi Hetilap
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