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Insuline + dpp4 inhibitor

Veronika Lappe, Ingrid Köster, Ingrid Schubert
: Background Ever since the UKPDS study reassessed the usefulness of the substance metformin in 1998, it has been the first-line medication in anti-diabetic treatment. In addition, new classes and agents released on the market have given rise to new treatment options. The present study investigates prescription practice at the onset of treatment and in the years thereafter and measures it against German diabetes guidelines. Database and Methods Database: Statutory health insurance sample AOK/KV Hesse; Ages: 40 and over (N = 142514)...
January 2017: Deutsche Medizinische Wochenschrift
Johanna H M Driessen, Joop P W van den Bergh, Hein A W van Onzenoort, Ronald M A Henry, Hubert G M Leufkens, Frank de Vries
AIMS: To investigate the association between long-term dipeptidyl peptidase-4 (DPP-4) inhibitor use and risk of fracture among people with type 2 diabetes mellitus (T2DM). METHODS: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink database (2007-2015), was conducted. All those (N = 328 254) with at least one prescription for a non-insulin antidiabetic drug (NIAD), aged ≥18 years at the time of data collection, were included...
December 10, 2016: Diabetes, Obesity & Metabolism
Mi-Kyung Kim, Yu Na Chae, Gook-Jun Ahn, Chang Yell Shin, Song-Hyen Choi, Eun Kyoung Yang, Yong Sung Sohn, Moon-Ho Son
Dipeptidyl peptidase 4 (DPP4) is an adipokine that interrupts insulin signaling. The resulting insulin resistance exacerbates hepatic steatosis. We previously reported that the novel DPP4 inhibitor evogliptin improves insulin resistance. This study aimed to verify the therapeutic potential of evogliptin for fatty liver. Evogliptin treatment was initiated simultaneously with a high-fat diet (HFD) feeding in normal mice and in a post-24 week HFD-fed rats. In a prevention study, insulin sensitivity was preserved in evogliptin-treated mice after a 16-week treatment...
November 24, 2016: Archives of Pharmacal Research
Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, George Liu
BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...
November 23, 2016: Lipids in Health and Disease
Sayantan Nath, Sankar Kumar Ghosh, Yashmin Choudhury
INTRODUCTION: A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS: Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day...
October 20, 2016: Journal of Pharmacological and Toxicological Methods
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
Heming Guo, Chen Fang, Yun Huang, Yufang Pei, Linqi Chen, Ji Hu
AIMS: Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel class of antidiabetic medication in the treatment of type 2 diabetes mellitus. Several studies have indicated that DPP4 inhibitors could be used for type 1diabetes (T1DM). Here, we performed a meta-analysis to assess the efficacy and safety of DPP4 inhibitor therapy in patients with T1DM. METHODS: We conducted searches on Medline, Cochrane Library, Web of Science, and EMBASE for relevant studies published before November 21, 2015...
November 2016: Diabetes Research and Clinical Practice
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Mohammad R Ashraghi, Gennaro Pagano, Sotirios Polychronis, Flavia Niccolini, Marios Politis
BACKGROUND: Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment...
2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Sivaporn Sivasinprasasn, Piangkwan Sa-Nguanmoo, Wanpitak Pongkan, Wasana Pratchayasakul, Siriporn C Chattipakorn, Nipon Chattipakorn
OBJECTIVE: Cardiac function was markedly compromised in obese insulin-resistant and estrogen-deprived rats. Metformin and dipeptidyl peptidase-4 inhibitor (vildagliptin) were reported to improve cardiac function in insulin-resistant rats. Their effects on the heart under estrogen-deprived conditions are, however, unknown. Therefore, the effects of metformin, vildagliptin, and estrogen on the cardiac function in estrogen-deprived insulin-resistant female rats were investigated. METHODS: Bilateral ovariectomized female rats (n = 48) were divided to be fed with either a normal diet (ND) or a high-fat diet (HFD) for 12 weeks...
August 2016: Menopause: the Journal of the North American Menopause Society
J F Gautier, P Monguillon, O Verier-Mine, P Valensi, B Fiquet, S Dejager, B Charbonnel
We conducted a pilot study to evaluate two therapeutic strategies at the time of insulin initiation in type 2 diabetic patients insufficiently controlled with metformin+insulin-secretagogues (IS, sulfonylureas or glinides). Patients were randomized to remain under the same dual therapy or to receive metformin+DPP4 inhibitors while starting insulin. Similar glycemic control was achieved in both groups. However less hypoglycemia was observed with DPP4 inhibitors despite higher doses of insulin.
June 2016: Diabetes Research and Clinical Practice
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
F Araújo, N Shrestha, M J Gomes, B Herranz-Blanco, D Liu, J J Hirvonen, P L Granja, H A Santos, B Sarmento
Oral delivery of proteins is still a challenge in the pharmaceutical field. Nanoparticles are among the most promising carrier systems for the oral delivery of proteins by increasing their oral bioavailability. However, most of the existent data regarding nanosystems for oral protein delivery is from in vitro studies, lacking in vivo experiments to evaluate the efficacy of these systems. Herein, a multifunctional composite system, tailored by droplet microfluidics, was used for dual delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 inhibitor (iDPP4) in vivo...
May 19, 2016: Nanoscale
Neha Shrestha, Francisca Araújo, Mohammad-Ali Shahbazi, Ermei Mäkilä, Maria João Gomes, Mikko Airavaara, Esko I Kauppinen, Janne Raula, Jarno Salonen, Jouni Hirvonen, Bruno Sarmento, Hélder A Santos
Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously...
June 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Atsushi Iida, Yusuke Seino, Ayako Fukami, Ryuya Maekawa, Daisuke Yabe, Shinobu Shimizu, Keita Kinoshita, Yusuke Takagi, Takako Izumoto, Hidetada Ogata, Kota Ishikawa, Nobuaki Ozaki, Shin Tsunekawa, Yoji Hamada, Yutaka Oiso, Hiroshi Arima, Yoshitaka Hayashi
AIMS/HYPOTHESIS: The action of incretin hormones including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) is potentiated in animal models defective in glucagon action. It has been reported that such animal models maintain normoglycaemia under streptozotocin (STZ)-induced beta cell damage. However, the role of GIP in regulation of glucose metabolism under a combination of glucagon deficiency and STZ-induced beta cell damage has not been fully explored...
July 2016: Diabetologia
C Klemann, L Wagner, M Stephan, S von Hörsten
CD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by N-terminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients...
July 2016: Clinical and Experimental Immunology
Tsuyoshi Mashitani, Ryuichi Noguchi, Yasushi Okura, Tadashi Namisaki, Akira Mitoro, Hitoshi Ishii, Toshiya Nakatani, Eiryo Kikuchi, Hiroto Moriyasu, Masami Matsumoto, Shinya Sato, Tatsuichi An, Hiroshi Morita, Sigeyuki Aizawa, Yasunori Tokuoka, Masatoshi Ishikawa, Yoshinobu Matsumura, Hiromasa Ohira, Atsuko Kogure, Kazuhiro Noguchi, Hitoshi Yoshiji
Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective anti-fibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes...
February 2016: Biomedical Reports
Jee Eun Lee, Jung Eun Kim, Mi Hwa Lee, Hye Kyoung Song, Jung Yeon Ghee, Young Sun Kang, Hye Sook Min, Hyun Wook Kim, Jin Joo Cha, Jee Young Han, Sang Youb Han, Dae Ryong Cha
Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls...
May 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Diana Röhrborn, Julia Brückner, Henrike Sell, Jürgen Eckel
DPP4 is a ubiquitously expressed cell surface protease which is also released to the circulation as soluble DPP4 (sDPP4). Recently, we identified DPP4 as a novel adipokine oversecreted in obesity and thus potentially linking obesity to the metabolic syndrome. Furthermore, sDPP4 impairs insulin signaling in an autocrine and paracrine fashion in different cell types. However, it is still unknown which functional role DPP4 might play in adipocytes. Therefore, primary human adipocytes were treated with a specific DPP4 siRNA...
March 11, 2016: Biochemical and Biophysical Research Communications
William B White, William L Baker
The incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, are important new classes of therapy for type 2 diabetes mellitus (T2DM). These agents prolong the action of the incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), by inhibiting their breakdown. The incretin hormones improve glycemic control in T2DM by increasing insulin secretion and suppressing glucagon levels. The cardiovascular (CV) effects of the incretin-based therapies have been of substantial interest since 2008, when the US Food and Drug Administration began to require that all new therapies for diabetes undergo rigorous assessment of CV safety through large-scale CV outcome trials...
2016: Annual Review of Medicine
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