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A REVIEW on the CURRENT DRUGS and NEW TARGETS for OBESITY Poojashree M J1*, Siddalingaprasad H S2, Swetha B R1, Shivukumar Swamy1

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A REVIEW on the CURRENT DRUGS and NEW TARGETS for OBESITY Poojashree M J1*, Siddalingaprasad H S2, Swetha B R1, Shivukumar Swamy1 11 Journal of Applied Pharmaceutical Research Volume 8, Issue 1, Year of Publication 2020, Page 11 – 21 DOI: 10.18231/j.joapr.2019.v.8.i.1.002 Review Article JOURNAL OF APPLIED PHARMACEUTICAL RESEARCH | JOAPR www.japtronline.com ISSN: 2348 – 0335 A REVIEW ON THE CURRENT DRUGS AND NEW TARGETS FOR OBESITY Poojashree M J1*, Siddalingaprasad H S2, Swetha B R1, Shivukumar Swamy1 Article Information ABSTRACT Received: 13th May 2019 Obesity is defined as the condition in which the Body Mass Index (BMI) of an individual is th Revised: 17 October 2019 between 25 and 29.5 that is ≥30kg/m2 and is caused by the imbalance management of energy th Accepted: 24 December 2019 intake and expenditure. Obesity is among the most prevalent diseases in the world and approximately over 10% of the people belong to overweight group in the world and over 5% in Keywords India. Currently many drugs are used to treat or to manage obesity. But these drugs also account Obesity, Diet, BMI, weight gain for several side effects. So there is an extensive need of promising drugs which can control obesity with greater efficacy and economic viability. This review focusses on the current drugs in the market used to treat obesity and also few of the new probable targets to discover drugs. INTRODUCTION China, India will occupy more than 50% of the obesity in the Obesity, the most common and complex disorders of this world. Currently, there are many drugs are used for the generation caused due to reasons like genetic heredity, diet and treatment of obesity but these drugs have numerous side environmental factors [1]. Obesity can be defined as a state of effects. Therefore, there is an extensive need of such a kind of an individual where the Body mass index (BMI) is more drugs which can control obesity with greater efficacy and 2 ≥30kg/m and is caused by the imbalance management of economic viability [3]. energy intake and expenditure. Obesity is more common in the Major pathogenesis occurs due to either over appetite or youngsters when compared to the elder people mainly due to dysregulation of energy utilizing functions in the body. This the lifestyle. Obesity has a major influence on social and kind of situation results in accumulation of fat that in turn psychological status of a person which eventually causes makes more adipose tissue. This alerts the secretion of cytokine depression. Physiologically it will also cause many of the in higher amount and thereby causes vascular complications diseases including cardiac problems [2]. In the world due to hyperlipidemia. This may in turn cause cardiovascular approximately 10% of the population belongs to overweight diseases and in most cases liver, gall stone and gut related group. Over 40 million children under age of 5 and 340 million diseases. Therefore management of the obesity is very much above the age of 5 are obese in the year 2016 [4, 5]. USA, essential to restrain these diseases [5]. It is very important to _______________________________________________________________________________________________ 1 Mallige College of Pharmacy, #71, Silvepura, Chikkabanavara Post, Bengaluru 560090 2 Department of Studies and Research in Biochemistry, Tumkur University, Tumakuru, Karnataka 572103 *For Correspondence: [email protected] ©2020 The authors This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY NC), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. (https://creativecommons.org/licenses/by-nc/4.0/) Journal of Applied Pharmaceutical Research 8 (1); 2020: 11 – 21 Poojashree et. al maintain the fatty acids, triglycerides and cholesterol in the between genetic and also environmental factors. All the People blood at very low level because higher amount of these who exposed urban and rural environments will become obese, molecules will start accumulating in the adipose all over the it means that there is some genetic mechanism working at the body called atherosclerosis and if it is not controlled may lead individual level. Hypothalamus expresses Leptin and to myocardial infarction and stroke. This also results in the Melanocortin-4 receptors, which are involved in the regulation increase of oxidative stress, lipotoxicity, hypertriglyceridemia of homeostasis in the neural circuits. Inefficiency to express and other complications like diabetes. Managing and reducing those proteins also brings obesity in the individuals [29]. the oxidative stress to prevent the obesity and few other People with multiple copies of FTO gene (Fat mass & obesity complications [5]. associated gene) are found to have 1.67 times higher risk of the Obesity anyhow can be managed either by reducing the obesity than the people who do not possess that extra copy of appetite or by enhancing the calorie utilization. Hunger and gene. satiety are managed by regulating the hormones which are Addition to insulin, glucagon, somatostatin, somatropin, responsible for hunger. However physical exercise can prevent cortisol, gastric inhibitory polypeptide/glucose-dependent the accumulation of white adipose [6]. The goal of treatment is insulinotropic peptide [GIP], adinopectin thyroxin, chemerin, to make the individual to attain and stay at healthy weight. The perilipin-1, apelin, GLP-1 catecholamines and cholecystokinin- preliminary treatment target is a sudden loss of weight of 5% to pancreozymin there are other 5 molecules which are produced 10% of the total weight. However, loss of more weight has endogenously have been found to regulate the apetite, satiety, greater benefits [7]. If the individual wants to reduce weight, storage of energy and metabolism. It includes Leptin, the person must change eating habits and do lot of physical Obestatin, Endocannabinoids, Ghrelin and Nesfatin-1 [29]. exercise [8]. The treatment methods which are right for the individual directly depend on the obesity severity, health and Current Drug based therapy for Obesity the enthusiasm in willingness in losing weight. Doctors may People with diabetes, sleep apnea, hypertension, arthritis and recommend medication for the weight loss only if the other hyperlipidemia have many risk factors for the treatment of plans like diet and exercise do not work [9]. Doctors will obesity using pharmacological therapy [30]. At present none of consider the health history of the person and possible side the drugs have been taken for clinical trials for more than 4 effects before choosing any medication for the obese patient years and also most of the drugs have serious side effects. [10]. Few of the medications can’t be given to pregnant women Treating obese person with drugs for a short period may have and to the people with chronic health diseases [11]. Plethora of side effects but it benefits for treating obesity. For any drug to information available in the literature suggests that variety of consider it as antiobesity drug, it should reduce the weight at drugs used treat obesity [12-26]. least by 2kg within 30 days and 5-8% in the next 180 days. Medication for obesity is so interesting and confusing that one Pharmacotherapy will be considered effective only if the medicine can’t react the same way to others and in few cases patient loses at least 10-15% of the initial weight in 1-2 years the effects may be slower as the time passes. Pausing or period [31]. After starting treatment, decrease in the weight stopping of the medication will result in the regain of the full or should be 10-15% of the initial weight within one year, then little weight which was lost. Keeping these things in mind, a only the demonstrated therapeutic drug will be called as anti- common, economically viable and effective drug is required to obesity drug. After losing weight, patients have to reduce the control obesity and with a proper diet plan which can intake of energy by 8kcal/kg [32]. substantially decrease the obesity of the individual. There are many agents used to treat obesity, they have different Physiological study of Obesity target and different mechanism of action. Appetite suppressant Development of obesity involves various pathological events at drugs, antidiabetic agents, anticonvulsant drugs, inhibitors of molecular level. Excess intake of food and less physical pancreatic lipase, serotonin 5-HT2c agonists, antidepressants, exercise leads to the condition of obesity [27]. A few number beta 3 adrenoceptor agonists, hormones and hormone of the cases are due to genetic inheritance, medical problems or analogues and other combinational formulae are the kind of psychiatric problems [28]. Obesity occurs due to the interplay drugs used in treating obesity. Clinician should select the type Journal of Applied Pharmaceutical Research (JOAPR)| January – March 2020 | Volume 8 Issue 1 | 12 Journal of Applied Pharmaceutical Research 8 (1); 2020: 11 – 21 Poojashree et. al of drug for each individual using the clinical trial data available physical exercise. Some of the approved antiobesity drugs are and prescribe the drug along with some diet restriction and listed in the Table 1. Table 1: Drugs which are approved by various authorities for treating obesity Drug Brand Treatment % or kg of Drug Mechanism of action Approved Reference name period weight loss authority EMA, FDA, Orlistat Xenical 4 years Approx. 3% TAG lipase inhibitor [33,34] ANVISA Buproban, Inhibits Noradrenaline and dopamine Bupropion Wellbutrin, 24 weeks
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