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Sitagliptin AND pancreatitis

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https://www.readbyqxmd.com/read/28432745/safety-of-sitagliptin-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-outcomes-from-tecos
#1
Samuel S Engel, Shailaja Suryawanshi, Susanna R Stevens, Robert G Josse, Jan H Cornel, Neli Jakuboniene, Axel Riefflin, Tsvetalina Tankova, Julio Wainstein, Eric D Peterson, Rury R Holman
AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14,528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR <60 mL/min per 1.73 m(2) ) versus those without CKD. Within the CKD cohort, the same analyses were performed comparing sitagliptin- and placebo-assigned participants...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28355570/pancreatic-%C3%AE-cell-derived-glucagon-related-peptides-are-required-for-%C3%AE-cell-adaptation-and-glucose-homeostasis
#2
Shuyang Traub, Daniel T Meier, Friederike Schulze, Erez Dror, Thierry M Nordmann, Nicole Goetz, Norina Koch, Elise Dalmas, Marc Stawiski, Valmir Makshana, Fabrizio Thorel, Pedro L Herrera, Marianne Böni-Schnetzler, Marc Y Donath
Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α cell ablation and with α cell-specific GLP-1 deficiency. Normally, intestinal GLP-1 compensates for the lack of α cell-derived GLP-1. However, upon aging and metabolic stress, glucose tolerance is impaired...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-after-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#3
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well-described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFAs) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance, and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323942/incretin-therapies-do-not-expand-%C3%AE-cell-mass-or-alter-pancreatic-histology-in-young-male-mice
#4
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, disagreement exists on whether incretins increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions, we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
June 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28283565/assessment-of-pancreas-safety-in-the-development-program-of-once-weekly-glp-1-receptor-agonist-dulaglutide
#5
Michael A Nauck, Jean-Louis Frossard, Jamie S Barkin, Greg Anglin, Ingrid E Hensley, Kristine D Harper, Zvonko Milicevic
OBJECTIVE: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks...
May 2017: Diabetes Care
https://www.readbyqxmd.com/read/28157387/trigonelline-attenuates-hepatic-complications-and-molecular-alterations-in-high-fat-high-fructose-diet-induced-insulin-resistance-in-rats
#6
Nehal A Afifi, Amer Ramadan, Emad Y Erian, Dalia O Saleh, Ahmed A Sedik, Manal Badawi, Walid El Hotaby
The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines...
April 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#7
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28078647/sitagliptin-a-review-in-type-2-diabetes
#8
REVIEW
Lesley J Scott
The dipeptidyl peptidase-4 inhibitor sitagliptin (Januvia(®); Glactiv(®); Tesavel(®); Xelevia™) is approved in more than 130 countries worldwide as monotherapy and in combination with other antihyperglycaemic drugs for the treatment of adult patients with type 2 diabetes (T2D). Extensive clinical experience has firmly established the glycaemic efficacy of oral sitagliptin (±other antihyperglycaemic drugs) in a broad spectrum of patients with T2D, including obese, elderly and renally impaired patients and those with established cardiovascular (CV) disease (CVD)...
February 2017: Drugs
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#9
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
March 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28057693/assessing-the-safety-of-sitagliptin-in-older-participants-in-the-trial-evaluating-cardiovascular-outcomes-with-sitagliptin-tecos
#10
M Angelyn Bethel, Samuel S Engel, Jennifer B Green, Zhen Huang, Robert G Josse, Keith D Kaufman, Eberhard Standl, Shailaja Suryawanshi, Frans Van de Werf, Darren K McGuire, Eric D Peterson, Rury R Holman
OBJECTIVE: Limited data exist regarding safety and efficacy of antihyperglycemic drugs in older patients with type 2 diabetes. The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) was a randomized, double-blind, placebo-controlled trial assessing the impact of sitagliptin on a primary composite outcome of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or unstable angina hospitalizations in patients with type 2 diabetes (HbA1c ≥6.5% [48 mmol/mol] and ≤8...
April 2017: Diabetes Care
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...
March 2017: Diabetes Care
https://www.readbyqxmd.com/read/27964837/efficacy-of-sitagliptin-for-the-hospital-management-of-general-medicine-and-surgery-patients-with-type-2-diabetes-sita-hospital-a-multicentre-prospective-open-label-non-inferiority-randomised-trial
#12
Francisco J Pasquel, Roma Gianchandani, Daniel J Rubin, Kathleen M Dungan, Isabel Anzola, Patricia C Gomez, Limin Peng, Israel Hodish, Tim Bodnar, David Wesorick, Vijay Balakrishnan, Kwame Osei, Guillermo E Umpierrez
BACKGROUND: The role of incretin-based drugs in the treatment of patients with type 2 diabetes admitted to hospital has not been extensively assessed. In this study, we compared the safety and efficacy of a dipeptidyl peptidase-4 inhibitor (sitagliptin) plus basal insulin with a basal-bolus insulin regimen for the management of patients with type 2 diabetes in general medicine and surgery in hospitals. METHODS: We did a multicentre, prospective, open-label, non-inferiority randomised clinical trial (Sita-Hospital) in five hospitals in the USA, enrolling patients aged 18-80 years with type 2 diabetes and a random blood glucose concentration of 7·8-22·2 mmol/L who were being treated with diet or oral antidiabetic drugs or had a total daily insulin dose of 0·6 units per kg or less, admitted to general medicine and surgery services...
February 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27882107/effects-of-sitagliptin-as-initial-therapy-in-newly-diagnosed-elderly-type-2-diabetics-a-randomized-controlled-study
#13
Xiaoyan Xiao, Xiaopei Cui, Jianbo Zhang, Zhenxia Han, Yu Xiao, Nan Chen, Baoying Li, Mei Cheng, Haiqing Gao, Kuanxiao Tang
The objective of this study was to investigate the characteristics of blood glycemic excursion, incretins and pancreatic hormone secretion in elderly people with newly diagnosed type 2 diabetes mellitus (T2DM) and to study the effects of sitagliptin on glycemic excursion in these subjects. A total of 129 newly diagnosed T2DM patients were enrolled in the study from March 2012 to August 2013. Clinical data, serum incretin, pancreatic hormone and continuous glucose monitoring data were collected. Among these subjects, elderly patients (NEDM) randomly received metformin combined with sitagliptin phosphate or glimepiride for 24 weeks...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27870481/glycemic-effect-and-safety-of-a-systemic-partial-glucokinase-activator-pf-04937319-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-on-metformin-a-randomized-crossover-active-controlled-study
#14
William S Denney, Douglas S Denham, Michael R Riggs, Neeta B Amin
Glucokinase enhances glucose conversion to glucose-6-phosphate, causing glucose-stimulated insulin secretion from pancreatic β cells and increased hepatic glucose uptake. PF-04937319 is a partial glucokinase activator designed to maintain efficacy with reduced hypoglycemia risk. In this randomized, double-blind, double-dummy, 3-period crossover phase 1b study, patients aged 18-70 years with type 2 diabetes mellitus and on metformin received once-daily PF-04937319 (300 mg), split-dose PF-04937319 (150+100 mg; breakfast+lunch), or sitagliptin (100 mg once daily)...
November 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27745828/efficacy-and-safety-of-dpp-4-inhibitors-in-patients-with-type-2-diabetes-meta-analysis-of-placebo-controlled-randomized-clinical-trials
#15
MULTICENTER STUDY
M B Rehman, B V Tudrej, J Soustre, M Buisson, P Archambault, D Pouchain, H Vaillant-Roussel, F Gueyffier, J-L Faillie, M-C Perault-Pochat, C Cornu, R Boussageon
BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial...
February 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/27659407/combined-analysis-of-three-large-interventional-trials-with-gliptins-indicates-increased-incidence-of-acute-pancreatitis-in-patients-with-type-2-diabetes
#16
Ivan Tkáč, Itamar Raz
OBJECTIVE: Data on the possible relationship of gliptin treatment to the incidence of acute pancreatitis have been controversial. The aim of the current study was to combine data on the incidence of acute pancreatitis from three large randomized controlled trials. RESEARCH DESIGN AND METHODS: Three trials designed to test cardiovascular safety and efficacy of add-on treatment with a gliptin were included in the analysis, as follows: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin)...
September 22, 2016: Diabetes Care
https://www.readbyqxmd.com/read/27630212/pancreatic-safety-of-sitagliptin-in-the-tecos-study
#17
John B Buse, M Angelyn Bethel, Jennifer B Green, Susanna R Stevens, Yuliya Lokhnygina, Pablo Aschner, Carlos Raffo Grado, Tsvetalina Tankova, Julio Wainstein, Robert Josse, John M Lachin, Samuel S Engel, Keyur Patel, Eric D Peterson, Rury R Holman
OBJECTIVE: We evaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i). RESEARCH DESIGN AND METHODS: In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, a cardiovascular safety study of sitagliptin, all suspected cases of acute pancreatitis and pancreatic cancer were collected prospectively for 14,671 participants during a median follow-up time of 3 years, and were adjudicated blindly...
February 2017: Diabetes Care
https://www.readbyqxmd.com/read/27459721/sitagliptin-treatment-after-total-pancreatectomy-with-islet-autotransplantation-a-randomized-placebo-controlled-study
#18
M D Bellin, G J Beilman, T B Dunn, T L Pruett, D E R Sutherland, S Chinnakotla, J S Hodges, A Lane, P Ptacek, K L Berry, B J Hering, A Moran
Insulin independence after total pancreatectomy and islet autotransplant (TPIAT) for chronic pancreatitis is limited by a high rate of postprocedure beta cell apoptosis. Endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are increased by dipeptidyl peptidase 4 inhibitor therapy (sitagliptin) may protect against beta cell apoptosis. To determine the effect of sitagliptin after TPIAT, 83 adult TPIAT recipients were randomized to receive sitagliptin (n = 54) or placebo (n = 29) for 12 months after TPIAT...
February 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27440852/liraglutide-improved-glycaemic-instability-in-a-patient-with-diabetes-with-insulin-antibodies
#19
Takehiro Kato, Katsumi Iizuka, Hiroyuki Niwa, Jun Takeda
Insulin antibodies sometimes cause glucose instability. A 52-year-old male patient was admitted to our department for the treatment of diabetes mellitus. From October 2003, he received insulin treatment for autoimmune pancreatitis and diabetes mellitus, but his hemoglobin A1c (HbA1c) levels gradually reached 8.0% (64 mmol/mol IFCC). In January 2010, insulin glargine and insulin aspart were introduced. In April 2010, the insulin antibody titre rose to >13.6 U/mL. In July 2010, treatment was changed to insulin glargine, metformin and miglitol...
July 20, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27042085/the-effect-of-sitagliptin-on-cardiovascular-risk-profile-in-korean-patients-with-type-2-diabetes-mellitus-a-retrospective-cohort-study
#20
Sooyoung Shin, Hyunah Kim
BACKGROUND: A 2013 postmarketing study suggested a possible link between saxagliptin use and hospital admission for heart failure. Cardiovascular (CV) effects of sitagliptin, the most commonly prescribed antidiabetic in the same class as saxagliptin, have not been evaluated much in Asian patients with type 2 diabetes. This study sought to ascertain the CV safety of sitagliptin in Korean patients. METHODS: A retrospective cohort study of 4,860 patients who were classified into the sitagliptin and metformin groups was conducted using electronic patient data retrieved from a major tertiary care medical center in Korea...
2016: Therapeutics and Clinical Risk Management
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