Review Article iMedPub Journals Journal of Childhood Obesity 2018 http://www.imedpub.com/ Vol.3 No.1:3 ISSN 2572-5394 DOI: 10.21767/2572-5394.100043 Pharmacological Advances to the Treatment of Obesity Milton E. Londoño-Lemos* Vice-Rectory of Research, Physiotherapy Program, Manuela Beltrán University, Bogotá D.C, Colombia *Corresponding Author: Milton E. Londoño-Lemos, Vice-Rectory of Research, Physiotherapy Program, Manuela Beltrán University, Bogotá D.C, Colombia, Tel: +571-5460600; Fax: +571-5460638; E-mail: [email protected] Received date: January 21, 2018; Accepted date: February 15, 2018; Published date: February 23, 2018 Citation: Londoño-Lemos ME (2018) Pharmacological advances to the treatment of obesity. J Child Obes Vol No 3 Iss No 1: 3. Copyright: © 2018 Londoño-Lemos ME. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. countries, men had higher rates of overweight and obesity, while women in developing countries showed higher rates, and Abstract in developed countries, the peak of obesity rates is moving at an earlier age presented in the following map (Figure 1) [2]. Obesity is one of the most serious problems of the 21st century and affects nearly 300 million people worldwide. According to the Organization for Economic Cooperation and Development (OECD), 18% of the adult population is obese. More alarming is the fact that there is a strong correlation between the development of childhood obesity and its prevalence in adulthood. Also, children who do not have this disease have a high probability of staying within normal weight in adulthood. Therefore, the presence of an early obesity predisposes to a prevalence of this condition in adult ages. The Food and Drug Administration (FDA) has approved five long-term obesity drugs for adults who are obese so far: lorcaserin, phentermine/topiramate, naltrexone/bupropion, Orlistat and liraglutide over the past two years. A fifth alternative, orlistat is a long-term Figure 1: Prevalence of obesity and overweight in the world. medication that is effective for up to six months and is the only drug used to treat childhood obesity. For this reason, new pharmacological alternatives are investigated. An important cause in the development of this disease is the Therefore, it is very important the knowledge of the increasing availability of foods rich in calories and High Fat Diet intestine-brain axis and hence leptin, which regulates food intake and energy balance in normal weight subjects and is (HFD), supported by lack of physical activity to increase energy a key hormone in food and body regulation in both children expenditure. Overweight and obesity significantly increase the and adults. risk of chronic non-communicable, premature mortality and the social cost of health. It is estimated that 90% of cases of type 2 diabetes mellitus are attributed to overweight and obesity. A Keywords: Obesity; Gastrointestinal system; Child child is considered obese when it exceeds 20% of its ideal obesity; Leptin; Diet weight, this problem not only triggers physical complications but also psychological. Generalities More alarming is the fact that there is a strong correlation between the development of childhood obesity and its Contextualization of obesity prevalence in adulthood. Likewise, children who do not present this disease have a high probability of staying within normal Obesity is one of the most serious problems of the 21st weight in adulthood [3]. Therefore, children who have an early century and today there is a record that about 2.1 billion people obesity predispose a prevalence of this condition during adult almost 30% of the world population are obese or overweight. stages. The rise in obesity rates worldwide over the last three decades has been substantial and widespread, presenting a public health epidemic in both developed and developing countries [1]. Pharmacological Treatment A systematic analysis of the Global Burden of Disease studies Obesity should be treated ideally with exercise and diet [4]. 2013 revealed that in Over the course of the study, overweight Indeed, the use of diets to control body weight in the long term and obesity rates among adults have increased for both men makes the vast majority of overweight or obese individuals have (from 29% to 37%) and women (from 30% to 38%). In developed to modify their type of diet to reduce daily energy intake. © Under License of Creative Commons Attribution 3.0 License | This article is available from: http://childhood-obesity.imedpub.com/ 1 Journal of Childhood Obesity 2018 ISSN 2572-5394 Vol.3 No.1:3 However, very low-calorie diets (VLCD, fewer than 800 kcal per digestive organs and adipose tissue; which are short-term day) or hypocaloric diets should not be used routinely. This indicators of the nutritional status (with the exception of leptin). should only be contemplated as part of a multicomponent strategy with specialist clinical support, where there is a need for rapid weight loss (such as prior to surgery). They should not be undertaken for more than 12 weeks [5]. VLCDs may not be nutritionally complete and provide far fewer calories than most people need to maintain a healthy weight. In addition, VLCDs may not be nutritionally complete and provide far fewer calories than most people need to maintain a healthy weight. It is not an easy diet to follow. Apart from feeling hungry and low on energy, other side effects can include: dry mouth, constipation or diarrhea, headache, dizziness, cramps, hair thinning While VLCDs can lead to short-term weight loss, most people tend to put the weight back on gradually after coming off the diet. Therefore VLCDs are not a long-term weight management Figure 2: Regulation of diet intake by gastrointestinal strategy and should only be used as part of a wider weight peptides and hormones at central and peripheral levels. management plan. Thus, it has been sought to promote the development of Such peripheral signals may be nerve impulses of the vague several pharmacological treatments to treat this disease. nerve induced by a series of hormonal peptides secreted and However, despite the discovery of the genetic basis of obesity generated just before and after meals (Table 1). [6] and the discovery of more than a dozen of hormones and peptides that regulate appetite, the obesity epidemic has not Table 1: Gastrointestinal hormonal peptides that control yet been halted [7]. appetite. Anti-obesity drugs developed so far Hormone Synthesis Site Main effects Developed drugs The Food and Drug Administration (FDA) in the United States They act in the CNS (ARC) of the hypothalamus has approved five long-term obesity drugs so far: Lorcaserin GIP K-cells of the Incretin effect on (Belviq®), Phentermine/Topiramate (Qsymia®), Naltrexone/ duodenum and insulin secretion; Bupropion (Contrave®), Liraglutide (Saxenda®) and Orlistat jejunum Increases the synthesis of fatty (Xenical®) for the long-term treatment of obesity. Medications acids in adipose like these can be used in combination with diet and exercise to tissue; Effects on food intake: help people lose weight [8]. unknown However, two of these drugs (phentermine/topiramate and GLP-1: Intestinal L Incretin effect on Natural analog of lorcaserin) did not obtain approval in Europe, due to safety peptide like cells insulin secretion; GLP-1 4-exendin. glucagon 1 Suppresses the Approved for the concerns [9]. release of treatment of type 2 glucagon; Inhibits diabetes. Liraglutide Medications approved for long-term obesity treatment, when gastric emptying; (Novo Nordisk) this used as an adjunct to lifestyle intervention, lead to greater mean Inhibits gastric drug has been secretion; Inhibits approved for use in weight loss and an increased likelihood of achieving clinically- energy intake diabetes meaningful 1-year weight loss relative to placebo. Weight loss ≥ 5% is generally considered to be clinically meaningful [10]. Oxyntomod L-cells of the Inhibits the ulin (OXM) distal intestine; production of Orlistat and Lorcaserine at 9% of the higher dose (15/92 mg) Post-prandial gastric acid; Phentermine plus prolonged release Topiramate at 1 year. The release after Reduces gastric food intake motility; Inhibits proportion of patients achieving at least 5% of clinically food intake; Stimulated by Decreased significant weight loss ranges from 37% to 47% for Lorcaserin, the presence plasma levels of of fatty acids 35% to 73% for Orlistat, and 67% to 70% for the higher dose Of Ghrelin Phentermine plus extended release Topiramate. All medications produce greater improvements in many cardio metabolic risk PYY (1-36) Synthesized by Inhibits food In humans it has L-type intake; Inhibits the been shown that the factors than placebo. There are many other medications, but not enteroendocrin secretion of the application of an approved for long-term use [11]. e cells, mainly gallbladder; intravenous infusion in the distal Reduces intestinal (I.V) of PYY (3-36), intestine. The motility; Inhibits decreases the food main pancreatic intake in a dose- The Intestine-Brain Axis circulating form secretion. dependent manner of this with a maximum Figure 2 [12,13] shows how the signals that stimulate hormone is inhibition of 35%; P responses in the regulation of intake in the brain come from the 2 This article is available from: http://childhood-obesity.imedpub.com/ Journal of Childhood Obesity 2018 ISSN 2572-5394 Vol.3 No.1:3 PYY (3-36), <0.001 vs. control) POMC, α-MSH binds to melanocortin MC3 and MC4 receptors. which is Withdrawn in 2005 The importance of the melanocortin system stems from the fact formed from adverse effect dose- the partial dependent nausea, that less than 6% of monkey obesity in humans has been rupture of PYY which would not be a observed to result from a defect in the MC4 receptor.