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Liraglutide and obesity

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https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#1
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28503750/comparative-effects-of-liraglutide-3%C3%A2-mg-versus-structured-lifestyle-modification-on-body-weight-liver-fat-and-liver-function-in-obese-patients-with-non-alcoholic-fatty-liver-disease-a-pilot-randomized-trial
#2
Joan Khoo, John Hsiang, Ranu Taneja, Ngai-Moh Law, Tiing-Leong Ang
We compared effects of weight loss induced by the glucagon-like peptide 1-agonist liraglutide with a structured lifestyle intervention in obese adults with non-alcoholic fatty liver disease (NAFLD). Obese (BMI ≥ 30 kg/m(2) , mean weight 96.0 ± 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on MRI without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/day) plus moderate-intensity aerobic exercise (~200 minutes/week) (DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks...
May 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28483802/glucagon-like-peptide-1-receptor-activation-augments-cardiac-output-and-improves-cardiac-efficiency-in-obese-swine-following-myocardial-infarction
#3
Daniel J Sassoon, Johnathan D Tune, Kieren J Mather, Jillian N Noblet, Mackenzie A Eagleson, Abass M Conteh, Joshua T Sturek, Adam G Goodwill
This study tested the hypothesis that glucagon-like peptide-1 therapies improve cardiac contractile function at rest and in response to adrenergic stimulation in obese swine following myocardial infarction. Obese Ossabaw swine were subjected to gradually developing regional coronary occlusion using an ameroid occluder placed around the left anterior descending coronary artery. Animals received subcutaneous injections of saline or liraglutide (0.005-0.015 mg/kg/day) for 30 days following ameroid placement. Cardiac performance was then assessed at rest and in response to sympathomimetic challenge (dobutamine 0...
May 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28481334/liraglutide-reduces-body-weight-by-upregulation-of-adenylate-cyclase-3
#4
Z Li, Y Liang, N Xia, Y Lai, H Pan, S Zhou, F Jiang, Y He
OBJECTIVE: According to recent studies, adenylate cyclase 3 (AC3) is associated with obesity. Liraglutide reduces blood glucose levels and body weight (BW). We performed a 2 × 2 factorial experiment to study the relationships among AC3, liraglutide and obesity and to obtain a more comprehensive understanding of the mechanisms underlying the physiological effects of liraglutide on obesity. METHODS: A high-fat diet was used to induce obesity in C57BL/6J mice. Both the normal and obese mice were treated with liraglutide (1 mg kg(-1)) or saline twice daily for 8 weeks...
May 8, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28473337/impact-of-liraglutide-on-amylase-lipase-and-acute-pancreatitis-in-participants-with-overweight-obesity-and-normoglycemia-prediabetes-or-type-2-diabetes-secondary-analyses-of-pooled-data-from-the-scale-clinical-development-program
#5
William M Steinberg, Julio Rosenstock, Thomas A Wadden, Morten Donsmark, Christine B Jensen, J Hans DeVries
OBJECTIVE: To describe amylase/lipase activity levels and events of acute pancreatitis (AP) in the SCALE (Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes) weight-management trials. RESEARCH DESIGN AND METHODS: Secondary analyses were performed on pooled data from four trials (N = 5,358 with BMI ≥30, or 27 to <30 kg/m(2) with ≥1 comorbidity). Of these, 1,723 had normoglycemia, 2,789 had prediabetes, and 846 had type 2 diabetes...
May 4, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28462892/effect-of-weight-reductions-on-estimated-kidney-function-post-hoc-analysis-of-two-randomized-trials
#6
Bernt Johan von Scholten, Melanie J Davies, Frederik Persson, Tine W Hansen, Sten Madsbad, Lars Endahl, Cecilie H Jepsen, Peter Rossing
AIMS: Weight loss-induced serum creatinine reduction may increase creatinine-based estimated glomerular filtration rate (eGFR) producing incorrect estimates of kidney function. We investigated whether weight changes in the SCALE program with liraglutide 3.0mg were associated with changes in serum creatinine. METHODS: Post hoc analysis of two 56-week, randomized, double-blind trials: SCALE Obesity and Prediabetes (n=3731, without type 2 diabetes [T2D], randomized [2:1] to liraglutide 3...
April 11, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28462579/pharmacological-management-of-obesity
#7
Amanda Velazquez, Caroline M Apovian
Current management of obesity includes three main arms: behavioral modification, pharmacologic therapy, and bariatric surgery. Decades prior, the only pharmacological agents available to treat obesity were approved only for short-term use (≤ 12 weeks) by the Food and Drug Administration (FDA). However, in the last several years, the FDA has approved several medications for longer term treatment of obesity. This highlights the important progression that we, as a society, better appreciate now the chronicity and complexity of obesity as a disease...
April 28, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28421338/tailoring-pharmacotherapy-to-specific-eating-behaviours-in-obesity-can-recommendations-for-personalised-therapy-be-made-from-the-current-data
#8
Carl A Roberts, Paul Christiansen, Jason C G Halford
Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28392927/liraglutide-for-weight-management-a-critical-review-of-the-evidence
#9
A Mehta, S P Marso, I J Neeland
OBJECTIVE: To review the efficacy, safety, and clinical applicability of liraglutide for weight management from phase III clinical trials. METHODS: A search of the English language literature was performed using PubMed search terms: "liraglutide", "glucagon-like peptide-1 receptor agonist", and "randomized clinical trial". Articles and bibliographies relevant to the subject were reviewed and additional references known to the authors were included. RESULTS: Five randomized, placebo-controlled trials of liraglutide for weight management were identified...
March 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/28386912/neuropsychiatric-safety-with-liraglutide-3-0%C3%A2-mg-for-weight-management-results-from-randomized-controlled-phase-2-and-3a-trials
#10
P M O'Neil, V R Aroda, A Astrup, R Kushner, D C W Lau, T A Wadden, J Brett, A Cancino, J P H Wilding
AIMS: Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Due to concerns over the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 kg/m(2) or ≥27 kg/m(2) with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3...
April 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28379427/tolerance-does-not-develop-toward-liraglutides-glucose-lowering-effect
#11
Tuuli Sedman, Eero Vasar, Vallo Volke
Context: Glucagon-like peptide-1 receptor agonists are popular antidiabetic drugs with potent glucose-lowering effects and low risk of hypoglycemia. Animal experiments and human data indicate that tolerance develops toward at least some of their effects, e.g., gastric motility. Whether tolerance develops toward the glucose-lowering effect of glucagon-like peptide-1 receptor agonists has never been formally tested. Objective: The objective of this pilot study was to test the hypothesis whether tolerance develops toward glucagon-like peptide-1 receptor agonists' glucose lowering effect in chronic use...
March 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28378293/pharmacotherapy-of-obesity-clinical-trials-to-clinical-practice
#12
REVIEW
Kishore M Gadde, Y Pritham Raj
PURPOSE OF REVIEW: This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice...
May 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28366815/liraglutide-suppression-of-caloric-intake-competes-with-the-intake-promoting-effects-of-a-palatable-cafeteria-diet-but-does-not-impact-food-or-macronutrient-selection
#13
Kellie M Hyde, Ginger D Blonde, Carel W le Roux, Alan C Spector
Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is used as a treatment for Type 2 diabetes mellitus and obesity because it improves glycemia and decreases food intake. Here, we tested whether chronic activation of the GLP-1 receptor system with liraglutide would induce decreases in intake accompanied by changes in proportional food or macronutrient intake similar to those seen following RYGB in rats when a variety of palatable food options are available. A "cafeteria diet" was used that included: laboratory rodent chow, refried beans (low-fat/low-sugar), low-fat yogurt (low-fat/high-sugar), peanut butter (high-fat/low-sugar) and sugar-fat whip (high-fat/high-sugar)...
March 30, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28351720/estradiol-effects-on-hypothalamic-ampk-and-bat-thermogenesis-a-gateway-for-obesity-treatment
#14
REVIEW
Miguel López, Manuel Tena-Sempere
In addition to their prominent roles in the control of reproduction, estrogens are important modulators of energy balance, as evident in conditions of deficiency of estrogens, which are characterized by increased feeding and decreased energy expenditure, leading to obesity. AMP-activated protein kinase (AMPK) is a ubiquitous cellular energy gauge that is activated under conditions of low energy, increasing energy production and reducing energy wasting. Centrally, the AMPK pathway is a canonical route regulating energy homeostasis, by integrating peripheral signals, such as hormones and metabolites, with neuronal networks...
March 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28292761/optimization-of-tolerability-and-efficacy-of-dual-amylin-and-calcitonin-receptor-agonist-kbp-089-through-dose-escalation-and-combination-with-a-glp-1-analogue
#15
Sofie Gydesen, Kim Vietz Andreassen, Sara Toftegaard Hjuler, Lars I Hellgren, Morten Asser Karsdal, Kim Henriksen
Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study, we investigated how to optimize tolerability, while maintaining efficacy of KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 potently activated both the amylin and calcitonin receptors in vitro, demonstrated a prolonged receptor activation, and potently reduced acute food intake. HFD rats dosed every or every second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and bodyweight in rats dosed every second day...
March 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28276830/bariatric-surgery-time-to-replace-with-glp-1
#16
Dominic-Luc Webb, Niclas Abrahamsson, Magnus Sundbom, Per M Hellström
Obesity with a body mass index (BMI) over 30 kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass...
June 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28276778/glp-1-receptor-agonists-in-the-treatment-of-polycystic-ovary-syndrome
#17
REVIEW
Elizabeth Mary Lamos, Rana Malek, Stephen N Davis
Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28254770/sglt2-inhibition-in-the-diabetic-kidney-from-mechanisms-to-clinical-outcome
#18
Erik J M van Bommel, Marcel H A Muskiet, Lennart Tonneijck, Mark H H Kramer, Max Nieuwdorp, Daniel H van Raalte
Diabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously...
April 3, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28245771/current-drug-targets-in-obesity-pharmacotherapy-a-review
#19
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of anti-obesity drugs has often been riddled with problems in the past...
February 27, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28237263/3-years-of-liraglutide-versus-placebo-for-type-2-diabetes-risk-reduction-and-weight-management-in-individuals-with-prediabetes-a-randomised-double-blind-trial
#20
Carel W le Roux, Arne Astrup, Ken Fujioka, Frank Greenway, David C W Lau, Luc Van Gaal, Rafael Violante Ortiz, John P H Wilding, Trine V Skjøth, Linda Shapiro Manning, Xavier Pi-Sunyer
BACKGROUND: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. METHODS: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m(2), or at least 27 kg/m(2) with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity...
April 8, 2017: Lancet
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