Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial

The Lancet Diabetes & Endocrinology, Journal Year: 2017, Volume and Issue: 5(4), P. 251 - 260

Published: Jan. 17, 2017

Language: Английский

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Semaglutide lowers body weight in rodents via distributed neural pathways

JCI Insight, Journal Year: 2020, Volume and Issue: 5(6)

Published: March 25, 2020

Semaglutide, a glucagon-like peptide 1 (GLP-1) analog, induces weight loss, lowers glucose levels, and reduces cardiovascular risk in patients with diabetes. Mechanistic preclinical studies suggest loss is mediated through GLP-1 receptors (GLP-1Rs) the brain. The findings presented here show that semaglutide modulated food preference, reduced intake, caused without decreasing energy expenditure. Semaglutide directly accessed brainstem, septal nucleus, hypothalamus but did not cross blood-brain barrier; it interacted brain circumventricular organs several select sites adjacent to ventricles. induced central c-Fos activation 10 areas, including hindbrain areas targeted by semaglutide, secondary direct GLP-1R interaction, such as lateral parabrachial nucleus. Automated analysis of access, activity, distribution, connectivity revealed may involve meal termination controlled neurons Transcriptomic microdissected from semaglutide-treated rats showed upregulation prolactin-releasing hormone tyrosine hydroxylase area postrema. We body interaction diverse populations indirectly affecting activity neural pathways involved reward,

Language: Английский

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Cardiovascular risk and obesity

Diabetology & Metabolic Syndrome, Journal Year: 2019, Volume and Issue: 11(1)

Published: Aug. 28, 2019

This is an overview of the mechanisms obesity and its relation to cardiovascular risks, describing available treatment options manage this condition. The pathogenesis includes balance between calories consumed energy expenditure followed by maintenance body weight. Diet, physical activity, environmental, behavioral physiological factors are part complex process weight loss, since there several hormones peptides involved in regulation appetite, eating behavior expenditure. complications associated also driven processes involving which include inflammation, insulin resistance, endothelial dysfunction, coronary calcification, activation coagulation, renin angiotensin or sympathetic nervous systems. Pharmacological treatments often needed insure loss as adjuncts diet activity people with overweight patients. To accomplish satisfactory goals, patients physicians seek for improvement risk condition, especially risk.

Language: Английский

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Obesity as a Disease

Medical Clinics of North America, Journal Year: 2017, Volume and Issue: 102(1), P. 13 - 33

Published: Oct. 23, 2017

Language: Английский

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Pharmacotherapy of obesity: an update on the available medications and drugs under investigation

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 58, P. 101882 - 101882

Published: March 21, 2023

Obesity is an epidemic and a public health threat. Medical weight management remains one of the options for treatment excess recent advances have revolutionized how we treat, more importantly will be treating obesity in near future. Metreleptin Setmelanotide are currently indicated rare syndromes, 5 other medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide) approved non-syndromic obesity. Tirzepatide about to approved, drugs, with exciting novel mechanisms action primarily based on incretins, being investigated different phases clinical trials. The majority these compounds act centrally, reduce appetite increase satiety, secondarily, gastrointestinal tract slow gastric emptying. All anti-obesity improve metabolic parameters, variable potency effects depending specific drug. available data do not support reduction hard cardiovascular outcomes, but it almost certain that such forthcoming very choice medication needs take into consideration patient's biochemical profile, co-morbidities, drug contra-indications, as well expected degree loss improvements cardio-renal risk. It also seen whether precision medicine may offer personalized solutions individuals obesity, represent future medical along development novel, potent, pipeline.FundingNone.

Language: Английский

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Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?

Current Obesity Reports, Journal Year: 2021, Volume and Issue: 10(1), P. 14 - 30

Published: Jan. 6, 2021

Language: Английский

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Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon‐like peptide‐1 receptor agonists: A systematic analysis of published clinical trials

Diabetes Obesity and Metabolism, Journal Year: 2016, Volume and Issue: 19(3), P. 336 - 347

Published: Nov. 10, 2016

GLP-1 receptor agonists (RAs) may cause nausea, vomiting or diarrhoea. The aim of this study was to assess the risk adverse events (AEs) with RAs and their relation dose, background medication duration action.The PubMed database searched 32 clinical trials (phase 3) were selected. We performed a systematic analysis compared proportion patients reporting diarrhoea, for different doses glucose-lowering medications, relative reference compound within subclasses short- (exenatide b.i.d.) long-acting (liraglutide) RAs, calculating risks ± 95% confidence intervals.The nausea dose-dependent (P = .0063) across all .0017), similar trend observed .23). Diarrhoea .031). Background treatment metformin associated more .04) .0009). Compared exenatide b.i.d., there less diarrhoea lixisenatide. liraglutide, dulaglutide, q.w. albiglutide. Long-acting vomiting, but than short-acting agents.GLP-1 are gastrointestinal AEs that related dose medications (especially metformin) vary in compound-specific manner. agents

Language: Английский

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Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function

Frontiers in Endocrinology, Journal Year: 2018, Volume and Issue: 9

Published: Nov. 23, 2018

The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its 'incretin effect' in restoring glucose homeostasis diabetics, however, it now apparent that has a broader range of physiological effects the body. Both vitro and vivo studies have demonstrated GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression influence neuroprotective pathways. A substantial body evidence accumulated with respect to how analogues act restore maintain normal cellular functions. These findings prompted several clinical trials which reported improve cardiac function, lung function reduce mortality patients obstructive disease, blood pressure lipid storage, even prevent synaptic loss neurodegeneration. Mechanistically, elicits via acute elevation cAMP levels, subsequent protein kinase(s) activation, pathways well defined pancreatic β-cells insulin secretion conjunction elevated Ca2+ ATP. More recently, new shed light on additional downstream stimulated by chronic exposure, direct relevance our understanding potential therapeutic longer lasting recently developed use. In this review, we provide comprehensive description diverse roles across multiple tissues, describe discuss novel pleiotropic applications treatment human disease.

Language: Английский

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Pharmacotherapy of obesity: Available medications and drugs under investigation

Metabolism, Journal Year: 2018, Volume and Issue: 92, P. 170 - 192

Published: Nov. 1, 2018

Language: Английский

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Obesity as a risk factor for Alzheimer's disease: weighing the evidence

Obesity Reviews, Journal Year: 2017, Volume and Issue: 19(2), P. 269 - 280

Published: Oct. 10, 2017

Alzheimer's disease (AD) is the sixth leading cause of death in USA today; therefore, it imperative that public health initiatives and clinical strategies are developed to prevent effectively treat AD. Despite enormous impact AD has on individuals, families, society, care system, there no biomarkers clearly identify those at risk for AD, prevention place, or treatments address underlying pathology stop progression There ample scientific as well empirical evidence obesity its metabolic vascular comorbidities related likely causative pathway. Obesity treatment could prove be an efficacious safe approach preventing a serious daunting epidemic disease. In this review, we present current pathophysiological linking obesity-related (eg, insulin resistance, hyperglycaemia, type 2 diabetes) with Additionally, discuss which population target when consider Finally, summarize regarding efficacy anti-obesity anti-diabetic pharmacotherapeutic agents

Language: Английский

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