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Liraglutide and obesity

Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill-defined. To address this gap, we evaluated the effects of an intravenous (IV) infusion of native OXM on insulin secretory rates (ISR) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo-controlled, single dose crossover trials in 12 overweight and obese subjects without diabetes, and in 12 obese subjects with Type 2 diabetes (T2DM) respectively, using the GLP-1 analog, liraglutide as a comparator in the T2DM...
March 15, 2018: Diabetes
Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Katerina Kapodistria, Effie-Photini Tsilibary, Eleni Kotsopoulou, Petros Moustardas, Paraskevi Kitsiou
Liraglutide, a human long-lasting GLP-1 analogue, is currently regarded as a powerful treatment option for type 2 diabetes. Apart from glucoregulatory and insulinotropic actions, liraglutide increases β-cell mass through stimulation of β-cell proliferation and islet neogenesis, as well as inhibition of β-cell apoptosis. However, the underline molecular mechanisms have not been fully characterized. In this study, we investigated the mechanism by which liraglutide preserves islet β-cells in an animal model of overt diabetes, the obese db/db mice, and protects a mouse pancreatic β-cell line (βTC-6 cells) against apoptosis...
March 10, 2018: Journal of Cellular and Molecular Medicine
Ilijana Babic, Ashleigh Gorak, Martin Engel, Dominic Sellers, Paul Else, Ashleigh L Osborne, Nagesh Pai, Xu-Feng Huang, Jessica Nealon, Katrina Weston-Green
BACKGROUND: Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment...
February 1, 2018: Journal of Psychopharmacology
V Chedid, P Vijayvargiya, P Carlson, K Van Malderen, A Acosta, A Zinsmeister, M Camilleri
BACKGROUND: Weight loss in response to the long-acting GLP-1 receptor (GLP1R) analog, liraglutide, is correlated with delay in gastric-emptying (GE). The aim of this pilot study was to assess whether specific genetic variants in GLP1R or TCF7L2 are associated with delayed GE and weight loss in obese patients treated with liraglutide or the short-acting GLP-1 agonist, exenatide. METHODS: We evaluated in obese individuals the associations of genetic variations of GLP1R (rs6923761) and TCF7L2 (rs7903146) on GE T1/2 and weight from two trials that evaluated separately exenatide, 5 μg BID for 30 days, or liraglutide, 3 mg daily for 5 weeks...
February 28, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Rodrigo B Mansur, Yena Lee, Mehala Subramaniapillai, Elisa Brietzke, Roger S McIntyre
Major depressive disorder and bipolar disorder are highly prevalent and disabling conditions. Cognition is considered a core domain of their psychopathology and a principle mediator of psychosocial impairment, disproportionately accounting for overall illness-associated costs. There are few interventions with replicated evidence of efficacy in treating cognitive deficits in mood disorders. Evidence also indicates that cognitive deficits are associated with obesity and involve significant impairment across multiple domains...
February 23, 2018: Neuropharmacology
Ariana M Chao, Thomas A Wadden, Robert I Berkowitz
Pediatric obesity is a serious public health concern. Five medications have been approved by the Food and Drug Administration (FDA) for chronic weight management in adults with obesity, when used as an adjunct to lifestyle modification. Orlistat is the only FDA-approved medication for pediatric patients aged 12 years and above. Areas covered: This paper summarizes safety and efficacy data from clinical trials of weight loss medications conducted among pediatric samples. Relevant studies were identified through searches in PubMed...
February 7, 2018: Expert Opinion on Drug Safety
E Capristo, S Panunzi, A De Gaetano, M Raffaelli, C Guidone, A Iaconelli, L L'Abbate, A L Birkenfeld, R Bellantone, S R Bornstein, G Mingrone
BACKGROUND/OBJECTIVES: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. SUBJECTS/METHODS: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age...
December 29, 2017: Diabetes & Metabolism
Dhiren K Patel, Fatima Cody Stanford
The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3...
February 8, 2018: Postgraduate Medicine
Tariq Chukir, Alpana P Shukla, Katherine H Saunders, Louis J Aronne
Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. Areas covered: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes...
January 29, 2018: Expert Opinion on Pharmacotherapy
Kirstine S Tølbøl, Maria Nb Kristiansen, Henrik H Hansen, Sanne S Veidal, Kristoffer Tg Rigbolt, Matthew P Gillum, Jacob Jelsing, Niels Vrang, Michael Feigh
AIM: To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis (NASH) in obese mouse models of biopsy-confirmed NASH. METHODS: Male wild-type C57BL/6J mice (DIO-NASH) and Lep ob/ob (ob/ob-NASH) mice were fed a diet high in trans-fat (40%), fructose (20%) and cholesterol (2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score (NAS) and fibrosis staging system...
January 14, 2018: World Journal of Gastroenterology: WJG
Michael A Nauck, Juris J Meier
Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known incretin hormones from the upper (GIP, K cells) and lower (GLP-1, L cells) gut. Together, they are responsible for the incretin effect: a two- to three-fold higher insulin secretory response to oral as compared to intravenous glucose administration. In subjects with type 2 diabetes, this incretin effect is diminished or no longer present...
February 2018: Diabetes, Obesity & Metabolism
Julie Rask Larsen, Lorena Dima, Christoph U Correll, Peter Manu
The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice...
January 31, 2018: Expert Review of Clinical Pharmacology
Yongmei Li, Jianying Du, Endong Zhu, Juanjuan Zhang, Jie Han, Wei Zhao, Bei Sun, Derun Tian
Liraglutide, as a glucagon-like peptide‑1 analogue, is used to treat type 2 diabetes mellitus and obesity. Previous findings have demonstrated the effects of liraglutide on adipogenesis; however, the underlying mechanism involved in this process remains to be elucidated. In the present study, to certify the effect of liraglutide on adipogenesis and explore the possible underlying mechanism involved in this process, preadipocyte 3T3‑L1 cells were cultured in adipocyte‑inducing medium and treated with liraglutide...
January 16, 2018: Molecular Medicine Reports
Vaia Lambadiari, George Pavlidis, Foteini Kousathana, Maria Varoudi, Dimitrios Vlastos, Eirini Maratou, Dimitrios Georgiou, Ioanna Andreadou, John Parissis, Helen Triantafyllidi, John Lekakis, Efstathios Iliodromitis, George Dimitriadis, Ignatios Ikonomidis
BACKGROUND: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months...
January 8, 2018: Cardiovascular Diabetology
Rohan Khera, Ambarish Pandey, Apoorva K Chandar, Mohammad H Murad, Larry J Prokop, Ian J Neeland, Jarett Berry, Michael Camilleri, Siddharth Singh
BACKGROUND & AIMS: We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications, approved by the Food and Drug Administration (FDA) for long-term use, on cardiometabolic risk profiles of obese adults. METHODS: We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of FDA-approved weight loss medications (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide), administered to obese adults for 1 year or more, compared with placebo or another active agent...
January 3, 2018: Gastroenterology
Kishore M Gadde, Corby K Martin, Hans-Rudolf Berthoud, Steven B Heymsfield
Obesity continues to be among the top health concerns across the globe. Despite our failure to contain the high prevalence of obesity, we now have a better understanding of its pathophysiology, and how excess adiposity leads to type 2 diabetes, hypertension, and cardiovascular disease. Lifestyle modification is recommended as the cornerstone of obesity management, but many patients do not achieve long-lasting benefits due to difficulty with adherence as well as physiological and neurohormonal adaptation of the body in response to weight loss...
January 2, 2018: Journal of the American College of Cardiology
L Engelbrechtsen, J Lundgren, N J Wewer Albrechtsen, Y Mahendran, E W Iepsen, P Finocchietto, A E Jonsson, S Madsbad, J J Holst, H Vestergaard, T Hansen, S S Torekov
Background: Dislipidaemia and increased levels of apolipoprotein B (apoB) in individuals with obesity are risk factors for development of cardiovascular disease (CVD). The aim of this study was to investigate the effect of weight loss and weight maintenance with and without liraglutide treatment on plasma lipid profiles and apoB. Methods: Fifty-eight individuals with obesity (body mass index 34.5 ± 3.0 kg/m2 [mean ± SD]) were included in this study. After 8 weeks on a very low-calorie diet (800 kcal/day), participants were randomized to weight maintenance with meal replacements with or without liraglutide (1...
December 2017: Obesity Science & Practice
Petr Sucharda
Weight loss drugs or anti-obesity drugs have a long history but are still far from being successful. Only in two last decades have the drugs been launched, which, when appropriately indicated, may be significantly beneficial to patients in need of weight loss as they are comparably effective to intensive programs to promote changes in eating habits and lifestyles. The combination naltrexone/bupropion is promising for food intake control including the reward mechanism, but the experience with its use has only been short-term...
2017: Casopís Lékar̆ů C̆eských
J Decara, P Rivera, S Arrabal, A Vargas, A Serrano, F J Pavón, C Dieguez, R Nogueiras, F Rodríguez de Fonseca, J Suárez
AIM: To explore the cooperation of GLP-1 receptor and β3-adrenergic receptor (β3-AR)-mediated signalling in the control of fat mass/feeding behaviour by studying the effects of a combined therapy composed of the GLP-1R agonist liraglutide and the β3-AR agonist CL316243. METHODS: The study included the analysis of key mechanisms regulating lipid/cholesterol metabolism, and thermogenesis in brown (BAT) and epididymal white (eWAT) adipose tissues, abdominal muscle and liver of male rats...
November 28, 2017: Acta Physiologica
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