Recently, the “epidemic of obesity” has emerged as one of the major global health concerns. Between 1975 and 2016, the worldwide prevalence...
Recently, the “epidemic of obesity” has emerged as one of the major global health concerns. Between 1975 and 2016, the worldwide prevalence of obesity tripled and was primarily attributed to the intake of a high calorie diet and a sedentary lifestyle [1]. Although the prevalence of being overweight was similar between men (39%) and women (40%) in 2016 according to the World Health Organization, recent studies have reported more rapid increases in obesity-related indicators in men than in women [2,3]. This sex disparity can be explained by genetic, sociocultural, socioeconomic, and behavioral factors [4]. After starting a career, men might succumb to obesogenic environmental changes— frequent dining outside the home, drinking, and stress, Received: Jan 13, 2020 Revised: Feb 5, 2020 Accepted: Feb 16, 2020 Published online Mar 9, 2020 Correspondence to: Sang Yeoup Lee https://orcid.org/0000-0002-3585-9910 Family Medicine Clinic, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea.
Tel: +82-55-360-1442, Fax: +82-51-510-8125, E-mail: saylee@pnu.edu Copyright © 2021 Korean Society for Sexual Medicine and Andrology Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review Young Jin Tak1,2 , Sang Yeoup Lee3,4 1 Department of Family Medicine, Pusan National University School of Medicine, Yangsan, 2 Biomedical Research Institute, Pusan National University Hospital, Busan, 3 Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, 4 Department of Medical Education, Pusan National University School of Medicine, Yangsan, Korea As a chronic and relapsing disease, obesity negatiⓇvely impacts the health of men to a greater extent than that of women, with a higher risk of cardiovascular disease. Since lifestyle modifications alone are often challenging and limited for the maintenance of weight reduction, pharmacotherapy should be considered in a timely manner for obese men or overweight patients with weight-related comorbidities. Recent advances in anti-obesity drugs have enabled the potential of achieving clinically significant weight loss. Increasing evidence has shown that behavior-based interventions with one of these medications can result in greater weight loss than that elicited by usual care conditions. Data from most recent meta-analyses showed that the overall placebo-subtracted weight reduction (%) with the use of anti-obesity drugs for at least 12 months ranges from 2.9% to 6.8%; phentermine/topiramate (-6.8%) liraglutide (-5.4%), naltrexone/bupropion (-4.0%), lorcaserin (-3.1%), and orlistat (-2.9%). However, they have a high cost and may cause adverse outcomes depending on the individual. Very recently, on February 13, 2020, the US Food and Drug Administration requested withdrawal of lorcaserin from the market because a safety clinical trial showed an increased occurrence of cancer.
Therefore the decision to initiate drug therapy in obese individuals should be made after the benefits and risks are considered. Thereafter, treatment should be tailored to specific patient subpopulations depending on their chronic conditions, comorbidities, and preferences. Herein, we provide an overview of the latest developments in weight loss medications, which may serve as one of the strategies for long-term obesity control. Keywords: Liraglutide; Lorcaserin; Naltrexone/bupropion; Obesity; Orlistat; Phentermine/topiramate This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Review Article pISSN: 2287-4208 / eISSN: 2287-4690 World J Mens Health 2021 Apr 39(2): 208-221 https://doi.org/10.5534/wjmh.200010 Metabolic syndrome and related conditions Young Jin Tak and Sang Yeoup Lee: An Updated Review on Anti-Obesity Drugs www.wjmh.org 209 which ultimately lead to high calorie intake [3]. Men also tend to have lower body image dissatisfaction than women. Resultantly, they tend to be less interested in the weight gained over time than women [5]. Excess fat distribution displays different patterns according to gender; it is concentrated in the centrally located visceral areas in men and subcutaneous areas in premenopausal women [6]. This difference may explain the greater negative impact of obesity on the cardiovascular health of men than on that of premenopausal women. Unlike subcutaneous fat, visceral fat is related to the worsening of insulin resistance and lipid and fluid metabolism [4]. Additionally, obesity in men predominantly reduces total testosterone due to the insulin resistance-associated decrease in sex hormonebinding globulin. Severe obesity is also related to reductions in free testosterone levels via suppression of the hypothalamic–pituitary–thyroid axis, whereas low testosterone alone results in increases in adiposity, thereby establishing a self-perpetuating cycle of metabolic impairment [7,8]. Previously, obese men were found to have a greater risk of erectile dysfunction (ED). In fact, obesity can cause vasculogenic ED, which has common features, including obesity-related metabolic alterations [9]. Timely and appropriate treatment to reduce excessive body fat is required in men with a body mass index (BMI) ≥30 kg/m2 (25 kg/m2 for some ethnic groups), ≥27 kg/m2 (23 kg/m2 for some ethnic groups) and obesity-related comorbidities or abdominal obesity (waist circumference [WC] ≥102 cm [90 cm for some ethnic groups]) [10,11]. Although intensive lifestyle modification, including calorie restriction and engaging in physical activities, is the first approach to ameliorate obesity, sustaining these efforts over a long period can be challenging and often prove insufficient [12]. Currently, most guidelines recommend pharmacotherapy as a second-line treatment for weight management after lifestyle modification [13,14]. In fact, numerous medications have been developed for the long-term management of obesity, with different mechanisms targeting various factors and diverse pathways that might cause a positive energy balance [15]. During the last decades, some anti-obesity drugs have been used to treat morbid obesity; however, most of these have been removed from the market owing to serious longterm side effects, particularly cardiovascular-related issues [16].
Since then, efforts to develop anti-obesity drugs have been made focusing on not only weight loss efficacy but also cardiovascular safety and lowered risk of cardiovascular disease (CVD). In recent years, the US Food and Drug Administration (FDA) has approved newer pharmacological options following more cautious studies elucidate their safety and efficacy [17]. As these anti-obesity drugs are approved for long-term management, they provide a better appreciation of the complex, chronic, and relapsing nature of obesity [18]. Importantly, the availability of different medications offers healthcare providers more options for deriving better patient-tailored treatment plans. In this review, we aimed to provide an overview of the latest developments in weight loss medications, which may serve as one of the strategies for long-term obesity control (Table 1). ANTI-OBESITY DRUGS FOR LONGTERM USE 1. Orlistat Orlistat (Xenical® ) was first approved by the FDA in 1999. Today, it remains the longest licensed antiobesity drug for long-term use and is available over the counter (Alli® ). As a non-central nervous system agent, orlistat 120 mg is prescribed for adults and adolescents ≥12 years of age [19]. 1) Mechanism of action Unlike other anti-obesity drugs on the market, orlistat does not exert its effect by affecting appetite; instead, it reduces calorie absorption. The main mechanism of orlistat is the inhibition of gastric and pancreatic lipases, which leads to a ~30% decrease in the absorption of intestinal triglycerides and thus calories [20]. Orlistat is expected to have little effect on weight loss with non-fatty food consumption. 2) Side effects Common side effects of orlistat include fatty/oily stools, increased defecation, fecal urgency, and flatus with discharge. However, by co-prescribing a fibercontaining supplement—psyllium, its gastrointestinal side effects can be reduced.
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