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.