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New-generation anti-obesity drugs: naltrexone/bupropion and liraglutide. An update for endocrinologists and nutritionists.
Barrea, L, Pugliese, G, Muscogiuri, G, Laudisio, D, Colao, A, Savastano, S
Minerva endocrinologica. 2020;(2):127-137
Abstract
The prevalence of obesity increases worldwide and has a significant economic impact on health care systems. A comprehensive program of lifestyle modification, including diet, exercise, and behavior therapy is considered the first option for achieving the significant weight loss. However, the intrinsic difficulties associated with maintenance of lifestyle changes contribute to the unsatisfactory long-term outcomes reported and weight regain in the obesity management. In this context, pharmacological approaches are useful to maximize non-pharmacological interventions in the long-term management of obesity. As add-on to lifestyle modification, pharmacological interventions are useful to facilitate clinically weight loss. In the past, anti-obesity drugs were limited. To date, the landscape has changed and naltrexone/bupropion and liraglutide have been recently added as new-generation anti-obesity drugs on obesity treatment and could represent important tools to manage of obesity. Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that shares 97% homology to native GLP-1 with effects on the limbic system. The treatment with liraglutide 3.0 mg, in combination with a hypocaloric diet and increased physical activity, provides a clinically meaningful weight loss. The combination of naltrexone 32 mg and bupropion 360 mg acts on the mesolimbic reward pathway and the hypothalamic hunger system, two areas of the central nervous system. The combination of naltrexone/bupropion, an adjunct to a hypocaloric diet and increased physical activity, is approved for chronic weight management in adults with obesity or overweight and ≥1 weight-related comorbidity. In the present review, we have focused on the current evidence on two new-generation anti-obesity drugs, naltrexone/bupropion and liraglutide 3.0 mg addressing the main studies that investigated these two new drugs for obesity treatment. Furthermore, evidence on semaglutide, currently in the pipeline for potential future therapeutic use for weight loss, are reported.
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Novel Antidiabetic Therapies and Cardiovascular Risk Reduction: The Role of the Noninferiority Trial.
Thompson, J, Schacht, S, Rothenberg, F
Cardiology clinics. 2019;(3):335-343
Abstract
Diabetes is a major risk factor for cardiovascular disease, yet until now treatments for diabetes had only a modest impact on cardiovascular events. New interventions for patients with type 2 diabetes mellitus (oral empagliflozin and injectable liraglutide) are associated with unprecedented reductions in composite cardiovascular outcomes that seem disproportionate to the impact on glycated hemoglobin. This review examines in detail the recent trials that arrived at these conclusions, limitations of these studies, and how these outcomes may influence patient management in the future.
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Diabetic kidney disease in 2017: A new era in therapeutics for diabetic kidney disease.
Wanner, C
Nature reviews. Nephrology. 2018;(2):78-80
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[Efficacy and safety of IdegLira for the intensification of type 2 diabetes treatment].
Costa Gil, JE, Faingold, MC, Fuente, GV, Litwak, LE, Rodríguez, M
Medicina. 2018;(4):225-233
Abstract
Diabetes mellitus is a true pandemic; type 2 diabetes in particular, with its progressive nature, constitutes a serious health problem. Despite advances and innovations in treatment, it continues to generate high morbidity and mortality. Many patients do not achieve their metabolic control objectives, due to clinical inertia, fear of hypoglycaemia, weight gain, the complexity of the treatment and the lack of adherence to it. Recently, the clinical results of the combined use of basal insulin and agonist receptor of the glucagon-like peptide type 1 (AR-GLP1) have been successfully evaluated. Therefore, the combined use of a basal insulin (insulin degludec) with an AR-GLP1 (liraglutide), in a single device (IdegLira), is proposed as an effective and safe therapeutic alternative for the treatment intensification in people with type 2 diabetes. IdegLira has shown greater reductions in HbA1c compared to its individual components, with a low risk of hypoglycaemia and weight loss, both in insulin naïve patients and in those previously insulinized. In this review we describe the pharmacology, the rational of the combination and the most relevant clinical evidence on IdegLira safety and efficacy.
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5.
Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity.
Burcelin, R, Gourdy, P
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2017;(1):86-98
Abstract
Over the past 30 years, there has been a dramatic rise in global obesity prevalence, resulting in significant economic and social consequences. Attempts to develop pharmacological agents to treat obesity have met with many obstacles including the lack of long-term effectiveness and the potential for adverse effects. Historically, there have been limited treatment options for overweight and obesity; however, since 2012, a number of new drugs have become available. A number of peptides produced in the gut act as key mediators of the gut-brain axis, which is involved in appetite regulation. This review discusses the role of the gut-brain axis in appetite regulation with special focus on glucagon-like peptide-1. Liraglutide 3.0 mg, a glucagon-like peptide-1 receptor agonist that targets this pathway, is now approved for the treatment of obesity and overweight (body mass index ≥27 kg/m2 ) with comorbidities such as type 2 diabetes, high blood pressure, high cholesterol or obstructive sleep apnoea. In addition, other glucagon-like peptide-1 receptor agonists offer promise for obesity management in the future. This review examines how glucagon-like peptide-1 receptor agonists promote weight loss and summarizes the clinical data on weight loss with glucagon-like peptide-1 receptor agonists.
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The Role of the Pharmacist in Managing Type 2 Diabetes with Glucagon-Like Peptide-1 Receptor Agonists as Add-On Therapy.
Meece, J
Advances in therapy. 2017;(3):638-657
Abstract
UNLABELLED The prevalence and associated clinical burden of type 2 diabetes (T2D) is increasing in the USA and other countries. As a consequence, the role of the pharmacist in managing T2D is expanding, and it is becoming increasingly important for pharmacists to have a complete understanding of the disease course and treatment options. Pharmacists have a key role in the use of injectable therapies, including incretin-based treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This article discusses the role of the pharmacist in the management of patients with T2D, particularly with respect to the use of GLP-1RAs to achieve glycemic control. GLP-1RAs are a class of injectable agents used as an adjunct to diet and exercise to improve glycemic control in adults with T2D. GLP-1RAs have been shown to lower glucose levels, slow gastric emptying, enhance satiety, and reduce body weight without increasing the risk of hypoglycemia. GLP-1RAs currently approved in the USA include exenatide twice daily, liraglutide once daily, and albiglutide, dulaglutide, and exenatide once weekly. Pharmacists can work with physicians to help identify patients for whom GLP-1RA therapy is appropriate. In addition, pharmacists can educate patients regarding medication storage, preparation, and injection techniques, glycated hemoglobin (HbA1c) targets, pre- and post-meal blood glucose goals, adverse events and management strategies, and the long-term benefits of reducing HbA1c. As members of the diabetes care team, pharmacists play an important role in improving patient outcomes. FUNDING AstraZeneca.
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7.
Liraglutide (Saxenda) for Weight Loss.
Whitten, JS
American family physician. 2016;(2):161-6
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[Pharmacotherapy for obesity].
Bruun, JM
Ugeskrift for laeger. 2016;(44)
Abstract
Obesity is a chronic condition, which is why pharmacotherapy can be considered, if lifestyle modification (hypocaloric diet/exercise) does not result in a weight loss of at least 5%. Pharmacotherapy is indicated, if an individual has a BMI > 30 kg/m2 or a BMI > 27 kg/m2 and concomitant disease (e.g. Type 2 diabetes), and can be liraglutide (3 mg) or orlistat (120 mg/60 mg). Choice of treatment must be based on patient preferences and clinical situation, side effects, contraindications and financial considerations. Weight loss of < 5% (about 4-5 kg) after 12 weeks should lead to cessation of the treatment.
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[Cardiovascular and renal protection of patients with type 2 diabetes : focus after EMPA-REG OUTCOME and LEADER].
Scheen, AJ, Piérard, L, Krzesinski, JM, Paquot, N
Revue medicale de Liege. 2016;(9):376-381
Abstract
Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with T2D and high cardiovascular risk : empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER. Both medications showed a significant reduction in major cardiovascular events (-14 and -13 %, respectively), cardiovascular mortality (-38 and -22%), all-cause mortality (-32 and -15 %) and renal events (-39 et -22 %). The underlying protective mechanisms remain controverted. Ongoing studies should allow to decide whether the benefits are specific to each molecule or may be attributed to a class effect.
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10.
Obesity in 2015: Advances in managing obesity.
Dixon, JB
Nature reviews. Endocrinology. 2016;(2):65-6