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https://www.readbyqxmd.com/read/28223856/uncertainties-around-incretin-based-therapies-a-literature-review
#1
REVIEW
Bader Al Tulaihi, Samia Alhabib
Background: Diabetes mellitus is a chronic debilitating and non-communicable disease. It has several long-term outcomes that are associated with various end organ damage, mainly the heart, blood vessels, eyes, nerves, and kidneys. There are different modalities of treatment of diabetes. The recent incretin-based therapies provided an innovative class of drugs including GLP-1 receptor agonists and DPP-4 inhibitors. This review aims to summarize the available evidence of their effectiveness. Method: This is a narrative review...
January 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28180064/dipeptidyl-peptidase-4-inhibitor-treatment-induces-a-greater-increase-in-plasma-levels-of-bioactive-gip-than-glp-1-in-non-diabetic-subjects
#2
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Hidemitsu Sakagami, Hiroya Kitsunai, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J Kieffer, Masakazu Haneda
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) possess multiple bioactive isoforms that are rendered non-insulinotropic by the enzyme dipeptidyl peptidase-4 (DPP-4). Recently, some ELISA kits have been developed to specifically measure "active" GIP and GLP-1, but it is unclear if these kits can accurately quantify all bioactive forms. Therefore, it remains uncertain to what extent treatment with a DPP-4 inhibitor boosts levels of biologically active GIP and GLP-1...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#3
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#4
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28169086/basal-insulin-treatment-intensification-in-patients-with-type-2-diabetes-mellitus-a-comprehensive-systematic-review-of-current-options
#5
REVIEW
D Raccah
AIM: As type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin...
February 3, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28127851/impact-of-insulin-sensitivity-beta-cell-function-and-glycemic-control-on-initiation-of-second-line-glucose-lowering-treatment-in-newly-diagnosed-type-2-diabetes
#6
Wolfgang Rathmann, Klaus Strassburger, Brenda Bongaerts, Pavel Bobrov, Oliver Kuss, Karsten Müssig, Daniel F Markgraf, Julia Szendroedi, Christian Herder, Michael Roden
AIMS: The aim was to investigate whether insulin sensitivity, beta-cell function or glycemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes. MATERIAL AND METHODS: Type 2 diabetes patients (n = 138) on initial metformin monotherapy (age [mean ± SD]: 52 ± 10 years; 67% males; BMI: 32 ± 6 kg/m(2) ) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under treatment of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp: M value; i...
January 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28120022/-cardiovascular-aspects-of-diabetes-treatment-finally-a-reason-for-cardiologists-to-be-pleased
#7
T Forst, L Plum-Mörschel, M M Weber
Cardiovascular disease significantly determines morbidity and mortality in patients with diabetes mellitus type 2. Large clinical trials in the past left controversial evidence about the effect of blood glucose-lowering treatments on cardiovascular outcomes. In 2008, the regulatory authorities defined new requirements on cardiovascular safety data for the approval of new drugs for the treatment of type 2 diabetes mellitus. Since then, numerous large safety studies have been initiated to prove cardiovascular noninferiority of new antidiabetic drugs...
January 24, 2017: Der Internist
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#8
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28036112/protocol-of-glucose-control-safety-and-efficacy-in-type-2-diabetes-a-network-meta-analysis-glucose-dinet-protocol-rational-and-design
#9
REVIEW
Guillaume Grenet, Audrey Lajoinie, Shams Ribault, Gia Bao Nguyen, Thomas Linet, Augustin Metge, Catherine Cornu, Michel Cucherat, Philippe Moulin, François Gueyffier
The aim of this study is to propose a ranking of the currently available antidiabetic drugs, regarding vascular clinical outcomes, in type 2 diabetic patients, through a network meta-analysis approach. Randomized clinical trials, regardless of the blinding design, testing contemporary antidiabetic drugs and considering clinically relevant outcomes in patients with type 2 diabetes mellitus will be included. The primary outcomes of this analysis will be overall mortality, cardiovascular mortality, and major cardiovascular events...
December 30, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#10
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27998910/pancreatic-effects-of-liraglutide-or-sitagliptin-in-overweight-patients-with-type-2-diabetes-a-12-week-randomized-placebo-controlled-trial
#11
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Mark H H Kramer, Indra C Pieters-van den Bos, Karuna E W Vendrik, Trynke Hoekstra, Marco J Bruno, Michaela Diamant, Daniël H van Raalte, Djuna L Cahen
OBJECTIVE: To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology. RESEARCH DESIGN AND METHODS: For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg (n = 19), sitagliptin 100 mg (n = 19), or matching placebos (n = 17) once daily for 12 weeks...
December 20, 2016: Diabetes Care
https://www.readbyqxmd.com/read/27997588/protective-effects-of-vildagliptin-against-pioglitazone-induced-bone-loss-in-type-2-diabetic-rats
#12
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Ju-Young Kim, Seung Hee Yu, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Kwang-Won Kim, Kiyoung Lee, Byung-Joon Kim
Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model...
2016: PloS One
https://www.readbyqxmd.com/read/27986341/incretin-related-drugs-and-cardiovascular-events-a-comparison-of-glp-1-analogue-and-dpp-4-inhibitor
#13
EDITORIAL
Yukihito Higashi
No abstract text is available yet for this article.
March 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/27976813/evaluation-of-drug-efficacy-of-dpp-4-inhibitors-based-on-theoretical-analysis-with-pharmacokinetics-and-pharmacodynamics
#14
Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada
Dipeptidyl peptidase-4 (DPP-4) inhibitors are used clinically as therapeutic agents for treatment of diabetes. To determine the rate of DPP-4 inhibition induced by these inhibitors, we used pharmacokinetic and pharmacodynamic parameters to theoretically examine the relationship between the rate of DPP-4 inhibition and clinical efficacy following administration of 4 different DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, linagliptin) by focusing on the increase in level of glucagon-like peptide-1 (GLP-1) induced by their administration...
December 15, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27933334/improved-glycaemia-in-high-fat-fed-neprilysin-deficient-mice-is-associated-with-reduced-dpp-4-activity-and-increased-active-glp-1-levels
#15
Joshua R Willard, Breanne M Barrow, Sakeneh Zraika
AIM/HYPOTHESIS: Neprilysin, a widely expressed peptidase, is upregulated in metabolically altered states such as obesity and type 2 diabetes. Like dipeptidyl peptidase-4 (DPP-4), neprilysin can degrade and inactivate the insulinotropic peptide glucagon-like peptide-1 (GLP-1). Thus, we investigated whether neprilysin deficiency enhances active GLP-1 levels and improves glycaemia in a mouse model of high fat feeding. METHODS: Nep (+/+) and Nep (-/-) mice were fed a 60% fat diet for 16 weeks, after which active GLP-1 and DPP-4 activity levels were measured, as were glucose, insulin and C-peptide levels during an OGTT...
December 8, 2016: Diabetologia
https://www.readbyqxmd.com/read/27898108/monotreme-glucagon-like-peptide-1-in-venom-and-gut-one-gene-two-very-different-functions
#16
Enkhjargal Tsend-Ayush, Chuan He, Mark A Myers, Sof Andrikopoulos, Nicole Wong, Patrick M Sexton, Denise Wootten, Briony E Forbes, Frank Grutzner
The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881129/impact-of-dipeptidyl-peptidase-4-inhibitors-on-serum-adiponectin-a-meta-analysis
#17
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
https://www.readbyqxmd.com/read/27862902/cardiovascular-events-and-all-cause-mortality-associated-with-sulphonylureas-compared-with-other-antihyperglycaemic-drugs-a-bayesian-meta-analysis-of-survival-data
#18
Steve Bain, Eric Druyts, Chakrapani Balijepalli, Carl A Baxter, Craig J Currie, Romita Das, Richard Donnelly, Kamlesh Khunti, Haya Langerman, Paul Leigh, Gaye Siliman, Kristian Thorlund, Kabirraaj Toor, Jiten Vora, Edward J Mills
AIM: To conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulphonylureas (SUs) vs other glucose lowering drugs in patients with T2DM (T2DM). MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane and clinicaltrials.gov was conducted for studies comparing SUs with placebo or other antihyperglycaemic drugs in patients with T2DM. A cloglog model was used in the Bayesian framework to obtain comparative hazard ratios (HRs) for the different interventions...
November 14, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27858848/a-genetic-variant-in-glp1r-is-associated-with-response-to-dpp-4-inhibitors-in-patients-with-type-2-diabetes
#19
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-Ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27844335/cardiovascular-safety-of-incretin-based-therapies-in-type-2-diabetes-systematic-review-of-integrated-analyses-and-randomized-controlled-trials
#20
REVIEW
Edoardo Mannucci, Matteo Monami
INTRODUCTION: Regulatory requirements mandate that new drugs for treatment of patients with type 2 diabetes mellitus (T2DM), such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, are evaluated to show that they do not increase cardiovascular (CV) risk. METHODS: A systematic review was undertaken to evaluate the association between DPP-4 inhibitor and GLP-1 receptor agonist use and major adverse cardiac events (MACE)...
January 2017: Advances in Therapy
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