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The Challenge of Obesity Treatment: a Review of Approved Drugs and New Therapeutic Targets

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The Challenge of Obesity Treatment: a Review of Approved Drugs and New Therapeutic Targets Review Article iMedPub Journals Journal of Obesity & Eating Disorders 2018 http://www.imedpub.com/ Vol.4 No.1:02 ISSN 2471-8203 DOI: 10.21767/2471-8203.100034 The Challenge of Obesity: A Review of Approved Drugs and New Beatriz Bonamichi1,2*, Erika Bezerra Parente2, Rafael Bonamichi dos Santos3,Rachel Beltzhoover1, Jongsoon Lee 1and Joao Eduardo Nunes Salles2 1Joslin Diabetes Center, Harvard Medical School, Boston 2Unit of Endocrinology in Santa Casa Medical School, Sao Paulo, SP, Brazil 3Brigham and Woman’s Hospital, Boston, MA, USA *Corresponding author: Beatriz Dal Santo Francisco Bonamichi, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA, Tel: +55 11 2176 7000; E-mail: [email protected] Received date: December 12, 2017; Accepted date: January 04, 2018; Published date: January 09, 2018 Citation: Bonamichi BDSF, Parente BE, dos Santos BR, Beltzhoover R, Lee J, et al. (2018) The challenge of obesity treatment: a review of approved drugs and new therapeutic targets. J Obes Eat Disord 4: 1. doi: 10.21767/2471-8203.100034 Copyright: © 2018 Bonamichi BDSF, et al. 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. Americans as being considered obese. Internationally, studies estimate that 1 billion people are overweight with Abstract approximately 500 million considered to be obese. Furthermore, weight averages are also increasing in both developed and Obesity is a metabolic dysfunction associated with a wide developing countries [4-6]. range of chronic illnesses that cause significant increases in comorbidity and mortality. According to the World Health It is also important to highlight that obesity has also been Organization, approximately 13% of the world’s population closely associated with an increased prevalence for is characterized as obese. Predictions state that these cardiovascular disease, hyperlipidemia, systemic arterial numbers are likely to increase exponentially in the future. hypertension and type 2 Diabetes, thus making obesity one of Due to this scenario, it is important to highlight the available the most significant of nutritional diseases [3]. treatments for obesity and to assess their effectiveness. Although obesity is an ancient disease, studies are Height and weight are the measurements currently used in constantly being conducted to improve treatment clinical practice to perform obesity diagnosis. One of the most effectiveness, reduce side effects of any current useful parameters to correlate height and weight is the Body medications, and identify new therapeutics targets. Because the treatment of obesity is constantly evolving, treatment Mass Index, (BMI) originally proposed by Quetelet. BMI is can be quite a challenge. Therefore, it is the objective of this calculated by dividing a person´s weight (in kilograms) by their review to provide a profile of the effectiveness of currently height squared (in meters) [7,8]. The World Health Organization approachable pharmacotherapy and indicate possible new defines obesity as a BMI of over 30 (Kg/m2) (Table 1) [9]. therapeutic targets. Table 1: Classification of obesity according to World Health Organization. Keywords: Obesity; Treatment; Pharmacotherapy BMI (Kg/m2) Classification Risk of related Introduction disease 18.5-24.9 Normal Normal Obesity is a potentially life-threatening, chronic disease. As the most prevalent metabolic disorder affecting humans today, 25.0-29.9 Overweight High obesity requires multidisciplinary, long-term treatment [1,2]. 30.0-34.9 Obesity class I Super high The worldwide prevalence of obesity has experienced a 35.0-40.0 Obesity class II Super super high remarkably steady increase. Yet treatment is essential because obesity has been linked to the onset of many other chronic >40.0 Obesity class III Established disease diseases, as well as higher rates of comorbidities and mortality *Modified by World Health Organization (104) [3-5]. Currently, obesity numbers reveal proportions indicative of a One of the most important requirements in the diagnosis and worldwide epidemic. Looking generally at the Canadian and U.S. follow up of obesity patients is their food history. Physicians population, approximately 50-60% may be classified as must work with the patient to determine dietary patterns and to overweight, while specifically indicating that about 35% of identify errors that contribute to their obesity [10]. It is © Under License of Creative Commons Attribution 3.0 License | This article is available from: 10.21767/2471-8203.100034 1 Journal of Obesity & Eating Disorders 2018 ISSN 2471-8203 Vol.4 No.1:02 extremely difficult, however, to assess the amount of food Phentermine/ 1 12.4% release of FDA intake, primarily because obese patients often underestimate topiramate year α (44) catecholamines and (Qsymia®) 9.6% inhibits excitatory (44, the amount of energy they consume [10,11]. Patient lifestyle is β (44) glutamate receptors 56) and carbonic also another important point to investigate, which should 5% δ anhydrase include: the frequency of physical activity, the environment in (56) which the patient consumes meals, and corrections for possible Sibutramine 1 4.21 inhibits 5-HT and ANVIS failures as being essential to successful treatment [10,11]. (Biomag®, Sibus®, year Kg norepinephrine A However, lifestyle changes are easier said than done, especially Saciette®) (18) (18) reuptake when considering those patients who have been found to have Rimonabant 1 4-7 Kg inverse agonist on * anxiety and their eating behavior is a manifestation of that (Acomplia®, year (105) the cannabinoid anxiety, or in other words, it is anxiety driven. The Redufast®) (105 receptor CB1 ) pathophysiology of obesity is multifactorial and complex and physicians may need to use the support of anxiolytics to help Lorcaserin (Belviq®) 1 5.8% Selective year (66,67 serotonergic 2C their patients control their eating behaviour. (66, ) receptor agonist 67) It should be noted that a reduction in body weight by 5-10% can improve blood pressure, blood glucose, serum lipids as well Liraglutide (Victoza® 1 5% GLP-1 receptor EMA, Saxenda®) year (73) agonist FDA, as improve individual health in most cases [12]. Therefore, in (73) ANVIS this report we have conducted a literature review of the latest A data on the efficiency and security of the drugs used to treat Empagliflozin 3 1.5 to sodium–glucose Phase I obesity, as well as future therapeutic targets (Table 2). (Jardiance®) year 2.0% cotransporter 2 s (76) inhibitor Table 2: Drugs used on obesity treatment (Approved by until (76) February 2017, FDA: Food and Drug Administration; EMA: Cetilistat (Cetislim®) 12 3.3 to inhibiting pancreatic Japan European Medicines Agency; ANVISA: National Health wee 4.1% lipase ks (78,79 Surveillance Agency, Weight loss: consider % and Kg since (78, ) baseline, *have already been approved, due to side effects, 79) require further study. α: phentermine 15.0 mg plus topiramate Belonarib 12 5.5 Kg inhibitor of Phase 92.0 mg, β: phentermine 7.5 mg plus topiramate 46.0 mg δ: wee Ω methionine II and ks aminopeptidase 2 III topiramate 15 mg Ω: 0.6 mg, ε: 1.2 mg, λ: 2.4 mg). 6.9 Kg (105 ε 10.9 ) kg λ Drug Tim Weig Mechanism Approv e ht ed by (105) loss Orlistat (Xenical®) 4 2.9% Triacylglycerol lipase EMA, Pharmacological treatment year (16,18 inhibitor FDA, s ) ANVIS Orlistat: Orlistat was approved in Europe in 1998 and (16, A 18) subsequently in the United States in 1999. Olistat, an inhibitor of gastrointestinal lipase, prevents the hydrolysis of triglycerides Bupropion 24 12.9% Noradrenaline and - (Buproban®, wee (22) dopamine reuptake into fatty acids and monoglycerides [13], thereby decreasing the Wellbutrin®, ks inhibitor absorption of fat in the intestines and calorie intake [13] which Zyban®) (22) then results in an increase in fecal fat excretion by 30% [14]. Naltrexone/ 24 6.1 to Opioid receptor EMA, bupropion wee 9.3% antagonist/ FDA Some studies demonstrated its efficacy in weight loss over (Contrave®) ks (33) Noradrenaline and periods of up to four years [13]. Modest effectiveness has been (33) dopamine reuptake inhibitor shown in combination with lifestyle intervention along with a reduction of 2.9 kg [95% CI, 2.27-3.51 kg] or 2.9% [95% CI, Bupropion/ 12 7.2 Kg Noradrenaline/ FDA 2.5-3.4%] of body weight greater than when compared to the zonisamide wee dopamine reuptake (37) ks inhibitor/ placebo [15-18]. (37) Mitochondrial carbonic anhydrase When being compared with the placebo, Orlistat, in the inhibitor Prevention of Diabetes in Obese Subjects clinical trial (XENDOS), Topiramate 24 6.5% inhibits excitatory * showed improvements in weight loss [5.8 Kg vs. 3.0 Kg; p<0.001] (Topamax®) wee (15) glutamate receptors [18] and revealed an important benefit in metabolic disorders ks and carbonic (15) anhydrase [17]. Furthermore, a meta-analysis of 15 trials with Orlistat demonstrated a mean placebo-adjusted weight reduction of Phentermine 24 7.2 to Noradrenergic EMA, nearly 2.9 kg (2.9%) in a follow up study after 4 years of (Adipex®) wee 8.1% sympathomimetic FDA ks (51) amine treatment [18]. (51) The main side-effects of Orlistat include gastrointestinal symptoms such as: diarrhea, flatulence, abdominal pain, oily or 2 This article is available from: 10.21767/2471-8203.100034 Journal of Obesity & Eating Disorders 2018 ISSN 2471-8203 Vol.4 No.1:02 liquid stool and fecal urgency [20]. These adverse effects also whereas by actively interfering with this system, the aim is to indicated Orlistat’s potential link to liver toxicity [19-21]. decrease food intake. In spite of its adverse effects, Orlistat is presently considered In March 2010, Naltrexone/Bupropion was delivered to the the most important obesity pharmacotherapy with long-term FDA, due to phase III trials in patients with no T2D, security and effectiveness.
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