Metabolism 133 (2022) 155217

Contents lists available at ScienceDirect

Metabolism
journal homepage: www.journals.elsevier.com/metabolism

A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19
pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on

A R T I C L E I N F O A B S T R A C T

Keywords The WHO just released in May 2022 a report on the state of the obesity pandemic in Europe, stating that 60% of
Prevalence citizens in the area of Europe are either overweight or obese, and highlighting the implications of the obesity
BMI pandemic, especially as it interacts with the COVID pandemic to create a twin pandemic, to increase morbidity
Adiposity
and mortality. Obesity is a complex disease which has reached pandemic dimensions. The worldwide prevalence
Obesity
Overweight
of obesity has nearly tripled since 1975, mainly due to the adoption of a progressively more sedentary lifestyle
Health risk and the consumption of less healthy diets. We first report herein updated prevalence rates of overweight and
obesity by sex, age, and region first in Europe, per the WHO report, and then worldwide between 1980 and 2019,
as we analyze and present herein the data provided by the Global Burden of Disease Study. The prevalence of
obesity is higher in women than in men of any age and the prevalence of both overweight and obesity increases
with age and has reached their highest point between the ages of 50 to 65 years showing a slight downward trend
afterwards. The age-standardized prevalence of obesity has increased from 4.6% in 1980 to 14.0% in 2019. The
American and European region have the highest obesity prevalence and the USA and Russia are the countries
with the most obese residents. Given dire implications in terms of comorbidities and mortality, these updated
epidemiological findings call for coordinated actions from local and regional governments, the scientific com­
munity and individual patients alike, as well as the food industry for the obesity pandemic to be controlled and
alleviated. We can hopefully learn from the COVID-19 pandemic, where collaborative efforts worldwide, focused
intense work at both the local and global level and well-coordinated leadership have demonstrated that hu­
mankind is capable of amazing accomplishments by leveraging science and public health, and that we can finally
make strides in terms of understanding and combating the obesity pandemic and its dire comorbidities including
diabetes, NAFLD, CVD and obesity associated malignancies.

1. Introduction to determine the degree of overweight or obesity. It is calculated using

the weight in Kg divided by the square of the height in meters and it is
Obesity is a chronic disease that is increasing in prevalence and is associated well with the percentage of body fat and body fat mass [14] in
now considered to be a global epidemic. Epidemiologic studies have most groups.
revealed an association between high body mass index (BMI) and an The sedentary lifestyle and the decline in overall physical activity in
extensive range of chronic diseases such as Non Alcoholic Fatty Liver combination with consumption of unhealthy diets, e.g. a high sugar and
(NAFL), cardiovascular disease [1,2], diabetes mellitus [1], several refined carb diet, building upon the myriad of genetic, endocrine,
malignancies [3,4], musculoskeletal diseases [5,6], chronic kidney dis­ metabolic, and environmental factors, are currently considered the main
ease [1], and mental disorders [7,8], which consequently, affect nega­ common causes for the obesity epidemic that is taking over many parts
tively subjects' quality of life and raise healthcare costs [9,10]. of the world during the last decades [15,16].
Interestingly, it has been demonstrated that BMI 30–40 kg/m2 is asso­ Studies examining the trends in obesity have shown that its preva­
ciated with almost 50%, and BMI over 40 kg/m2 is associated with 100% lence has raised in all age groups, regardless the ethnicity or socioeco­
greater healthcare expenditures due to treatment of obesity comorbid­ nomic status [17]. From 1999 through 2018, the obesity prevalence in
ities [11]. Similarly, BMI >30 kg/m2 has been linked with an increase in the United States increased from 30.5% to 42.4%. Notably, the obesity
annual healthcare costs of approximately 37% [12]. prevalence was 40% among adults aged 20 to 39 years, 45% among
The World Health Organization (WHO) defines overweight as BMI adults aged 40 to 59 years, and 43% among the group aged 60 years and
>25 kg/m2 and obesity >30 kg/m2 and describes these conditions as older.
abnormal or excessive fat accumulation that is associated with increased Prevalence data on obesity have been obtained using two platforms
health risk. BMI, although not the most accurate metric of excess fat in the USA; the annual phone call surveys conducted by state De­
[13], is easy to assess and is thus the most commonly accepted first step partments of Health in collaboration with the Centers for Disease

https://doi.org/10.1016/j.metabol.2022.155217
Received 10 May 2022; Accepted 11 May 2022
Available online 15 May 2022
0026-0495/© 2022 Elsevier Inc. All rights reserved.
C. Boutari and C.S. Mantzoros Metabolism 133 (2022) 155217

Control and Prevention (the Behavioral Risk Factor Surveillance System WHO European Region, impairing almost 60% of adults [20]. Children
[BRFSS]), and surveys by the National Center for Health Statistics as the are also affected, with almost 8% of children younger than 5 years and
National Health and Nutrition Examination Survey (NHANES), one in three school-aged children living with overweight or obesity.
providing a sample selected through a complex, multistage probability Prevalence decreases temporarily in the age group 10–19 years, where
design [18]. The age-adjusted prevalence of obesity among US adults one in four live with overweight or obesity. Repercussions of obesity on
based upon data collected for NHANES was 42.4% in 2017–2018. Data health include those that result from the mechanical effects of excess
from BRFSS consistently report obesity prevalence rates lower than body weight, such as some musculoskeletal complications, metabolic
those from the NHANES surveys (30.9% in 2019), probably due to the effects such as diabetes and cardiovascular risk, and the effects on
self-report bias on phone surveys. Moreover, the CDC report on obesity mental health. Obesity is also considered to be responsible for more than
prevalence in the USA estimates that 31.4% of adults were obese in 2019 13 types of malignancies. Overweight and obese people have been
[19]. Thus, it is crucial to identify the data source when evaluating disproportionately impaired by the effects of the COVID-19 pandemic.
obesity prevalence information. It would also be interesting to evaluate The report concludes by recommending a series of interventions in
and report the prevalence of obesity in the USA and the world in the post general population and policy options that Member States can follow in
COVID-19 pandemic, a pandemic that caused 15 million deaths (esti­ preventing and managing obesity in the Region, focusing on building
mates vary between 12 and 22 million) during the past two years and back better after the COVID-19 pandemic.
mainly deaths of patients with obesity and metabolic comorbidities.
On the occasion of the newly released WHO report on the status of 3.2. Global burden of disease study results
Obesity in the European region stating that both overweight and obesity
rates have reached epidemic proportions across the European Region, 3.2.1. Prevalence of overweight and obesity by sex and age
where 59% of adults and almost 1 in 3 children are suffering from Fig. 1 depicts the global prevalence rates of overweight and obesity
overweight or obesity [20], we publish this report as an update on the in 2019, for men and women over 20 years, by age group. In 2019, the
epidemiology of obesity [21]. The purpose of this update is to re- prevalence of overweight was slightly lower in young females than in
evaluate the global and regional prevalence and trends of overweight young males aged 20–44 years whilst this trend was inverted among the
and obesity given the new advances in our knowledge on the patho­ age groups over 45 years, probably because of the menopause occurring
physiology of obesity and the resultant new therapeutic tools that have in women. The prevalence of obesity is in general higher in women than
been introduced recently in the field [22,23]. The purpose of this update in men of any age. [Fig. 2] The prevalence of both overweight and
is also to draw attention to the obesity pandemic, and the need for more obesity increased with age, reached their highest point between the ages
research and care and public health efforts as a call to action. Now that of 50 to 65 years, and showed a slight downward trend afterwards.
the COVID-19 pandemic appears to be receding, we need to learn from
our successes in that front as we prioritize work on the other pandemic, 3.2.2. Global trends in obesity
that of obesity and its comorbidities e.g. diabetes which will continue to The age-standardized prevalence of obesity increased from 4.6% in
plague our society unless global leaders provide the guidance and re­ 1980 to 14.0% in 2019. Half of this rise occurred in 22 years between
sources needed to create a meaningful difference. 1980 and 2002 and another half occurred in the 17 years between 2002
and 2019. A constant predominance of women in the prevalence rates of
2. Methods obesity compared to men is observed. [Fig. 3].

We report data from the May 2022 European Regional Report on 3.2.3. Regional prevalence of obesity
Obesity by the WHO. We also used the data published from the Global The highest prevalence of obesity was observed in the American and
Burden of Disease Study (Institute for Health Metrics and Evaluation, the European region. In the Americas, the prevalence of obesity
Seattle, WA) [17]. The full data file is available online from Global increased from 6.8% in 1980 to 22.4% in 2019. The countries with the
Health Data Exchange (http://ghdx.heathdata.org). highest prevalence rates were the United States (23.2%) and Mexico
We adopted the WHO division of the world into six regions; namely (18.4%), while Colombia had the lowest prevalence rate of obesity
African, Americas, Eastern Mediterranean, European, South East Asian, (9.8%). Likewise, in Europe, the rates increased from 8.4% in 1980 to
and Western Pacific. We isolated the data for the five most populous 20% in 2019 and the countries with the highest percentage of obese
countries from each region: the African region included Nigeria, inhabitants were Russia (15.9%) and Turkey (17.5%). France had the
Ethiopia, Congo, the United Republic of Tanzania, and South Africa; the lowest rate of obesity prevalence (10.3%).
Americas included the United States of America, Brazil, Mexico, In the Eastern Mediterranean region, the prevalence of obesity
Colombia, and Argentina; the Eastern Mediterranean included Pakistan, increased from 6.4% to 17.4% in 2019, while in the African region the
Egypt, Iran, Iraq, and Afghanistan; the European region included prevalence of obesity increased from 3.8% to 10.9%. Some countries in
Russian Federation, Germany, Turkey, United Kingdom, and France; the these two regions presented much fluctuation in the prevalence rates of
South East Asian region included India, Indonesia, Bangladesh, Thailand obesity. For instance, this rate in South Africa increased from 11.8% in
and Myanmar; and finally, the Western Pacific region included China, 1980 to 23.3% in 2019, and in Iran from 5.9% in 1980 to 20.1% in 2019.
Japan, Philippines, Viet Nam, and Republic of Korea. The aforemen­ Finally, as for the region with the lowest obesity prevalence rates, the
tioned selected countries represent ~78% of the world's population. West Pacific, the prevalence of obesity increased approximately fivefold,
We report prevalence rates (%) of overweight and obesity by sex, from 0.9% in 1980 to 5% almost 40 years later. Particularly, in China,
age, and region between 1980 and 2019. the prevalence of obesity increased from 0.4% to 5.8%. In parallel, the
prevalence rate of obesity in the South East Asian region started from the
3. Results same level as that of the West Pacific (0.9% in 1980) and showed a larger
increase reaching 7.9% in 2019. [Fig. 4].
3.1. Prevalence of overweight and obesity in the European region by the In general, rising trends in the prevalence rates of both obesity and
WHO overweight are observed globally over the last 4 decades.

Obesity has been recognized as an important public health issue 4. Discussion

globally and a major determinant of morbidity and mortality in the
WHO European Region which raises the risk of noncommunicable dis­ The worldwide prevalence of obesity has nearly tripled between
eases. Overweight and obesity have reached epidemic dimensions in the 1975 and 2016 and has now reached pandemic dimensions [14].

2
C. Boutari and C.S. Mantzoros Metabolism 133 (2022) 155217

Global prevalence of overweight

60%

50%

40%

30%

20%

10%

0%
20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80+
Males Females Both
Fig. 1. Global prevalence of overweight in adults >20 years old by age group and sex (ca. 2019). [Data from the Global Burden of Disease Study (Institute for Health
Metrics and Evaluation, Seattle, WA)] [17].

Global prevalence of obesity

30%

25%

20%

15%

10%

5%

0%
20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

Men Women Both

Fig. 2. Global prevalence of obesity in adults >20 years old by age group and sex (ca. 2019). [Data from the Global Burden of Disease Study (Institute for Health
Metrics and Evaluation, Seattle, WA)] [14].

Specifically, the global obesity prevalence has risen approximately 2 on the rise in low- and middle-income countries due to the global free
percentage points per decade [24]. According to the WHO, there are trade, the economic growth and the urbanization these countries are
about 2 billion adults who are overweight, whilst 650 million are obese. experiencing [27]. Moreover, it has been reported that obesity is
If these rates do not slow down, it is expected that 2.7 billion adults will concentrated among the rich in low-income countries and the poor in
be overweight and over 1 billion will be obese by 2025. The prevalence high-income countries [28]. There are several reasons for this. As the
of obesity increased markedly between 1980 and 2019 from 3.2% to income rises people can afford more food. In parallel, their dietary
12.2% in men, and from 6% to 15.7% in women. The fact that females habits change and become more ‘westernized’. Also, the rich adopt a
constantly lead in terms of the proportions of obesity is expected, given more sedentary lifestyle and occupation. However, this pattern changes
the biologically driven higher percentage of body fat in women [25,26]. at the societies with higher levels of income where the social stigma of
Fundamental sex differences include distribution and mobilization of being obese prevails. Moreover, access to healthy diets, healthcare,
adipose tissue storage, different insulin sensitivity and lipoprotein pro­ education, and activities promoting weight loss is improved in high-
files, and effects of gonadal hormones. Although overweight and obesity income countries.
are considered a high-income country problem, they both are currently Obesity prevalence increased in every single country of the world.

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C. Boutari and C.S. Mantzoros Metabolism 133 (2022) 155217

Global trends in obesity

16%

14%

12%

10%

8%

6%

4%

2%

0%
1980 1985 1990 1995 2000 2005 2010 2015 2020

Males Females Both

Fig. 3. Age-standardized global prevalence of obesity in men and women >20 years old by year (ca. 1980–2019). [Data from the Global Burden of Disease Study
(Institute for Health Metrics and Evaluation, Seattle, WA)] [17].

Regional trends in obesity

25%

20%

15%

10%

5%

0%
1980 1985 1990 1995 2000 2005 2010 2015 2020

African Americas East Mediterranean

European South East Asian West Pacific

Fig. 4. Age-standardized prevalence of obesity in adults >20 years old by geographical region and year (ca. 1980–2019). [Data from the Global Burden of Disease
Study (Institute for Health Metrics and Evaluation, Seattle, WA)] [17].

Interestingly, 12 countries had a prevalence of obesity under 2% in Nigeria, Ethiopia, Tanzania, Pakistan, Afghanistan, India, Bangladesh,
1980: Ethiopia (0.4%), Pakistan (1.7%), India (0.9%), Indonesia (1.0%), Myanmar, China, Japan, Philippines, Viet Nam, Korea. Interestingly, 9
Bangladesh (0.3%), Thailand (1.9%), Myanmar (0.5%), China (0.4%), countries had a prevalence of obesity >20%: South Africa (23.3%), USA
Japan (1.6%), Philippines (1.8%), Viet Nam (0.5%), and Korea (0.7%). (32%), Brazil (21.4%), Mexico (25%), Egypt (30%), Iran (20.1%), Iraq
Hunger is high even today in almost all subregions of Africa and to a (21%), Russia (21.5%), Turkey (26%).
lesser extent in Latin America and Western Asia, and a large portion of Alterations in the global food system in combination with the
people in those regions experience moderate or severe food insecurity. adoption of a sedentary lifestyle represent the main drivers of the
Nevertheless, a considerable rise in caloric supply across Asia and Africa obesity pandemic. In addition, regional differences are largely associ­
is observed in recent decades [29]. Of note, nowadays, there is no ated with differences in socioeconomic status [30]. Poverty, aspects of
country with obesity prevalence below 2%. the food environment (e.g., accessibility to fast-food restaurants and/or
The absolute rates of obesity varied considerably among regions and supermarkets, groceries), community characteristics (e.g., cultural
countries. In 1980, the obesity prevalence rates ranged from 0.3% in norms, education, the way towns are built), and ideal weight and body
Bangladesh to 12.8% in the USA and in only 5 countries the prevalence image unique to particular regions are some of the underlying factors
rate was over 10%: South Africa (11.8%), USA (12.8%), Egypt (10.7%), impairing regional disparities in obesity prevalence. It is also of great
Iraq (10.3%), Russia (11.8%). In 2019, obesity prevalence rates ranged interest that the economic disparity within a society may cause het­
from 3.5% in Bangladesh to 32% in the USA and only 13 out of the 30 erogeneity in obesity prevalence [31,32]. It has been advocated that
countries examined had an obesity prevalence rate less than 10%: wider income gaps cause wider waists [31]. Moreover, at a given BMI,

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C. Boutari and C.S. Mantzoros Metabolism 133 (2022) 155217

Asian populations apparently have higher health risks in comparison to the pandemic’ but the lower virulence of the Omicron variant of SARS-
Caucasians and this may result from the different fat distribution, i.e. CoV-2, in conjunction with the increasing coverage of the populations
more central body fat distribution, these populations have [33]. BMI by vaccination and the reduced burden on healthcare systems create
does not assess body fat directly and in younger population may also hope for a subdued pandemic. Disappointingly, and in contrast to the
reflect muscle mass. The relationship between BMI and body fat is COVID-19 pandemic, the obesity epidemic is continuing to worsen, and
related to the body composition of a specific person and is also affected it is acknowledged as a global public health issue which continues to
by sex, age, race, and origin. On the other hand, the waist-to-hip ratio growth in significance.
(WHR) is assumed to reflect more accurately the distribution of fat. The COVID-19 pandemic had an unprecedented impact on research
Variation in waist circumference reflects mainly variation in subcu­ and education for medical and healthcare professions. Healthcare pro­
taneous and visceral fat, whereas variation in hip circumference repre­ fessionals have been forced to concentrate on COVID-19 patients and,
sents variation in bone structure (pelvic width), gluteal muscle, and for a long time, not seeing and caring for the patients in their own
subcutaneous gluteal fat [34]. However, the considerable fluctuation in clinics. The education of medical students has been discontinued and the
methodology used in the field and the results reported in the literature, graduation of many final year students was expedited so they could start
apparently reflect the lack of a standardized approach [35]. work as junior doctors on the frontline of the COVID-19 pandemic
Another important issue is the observed gender gap in obesity rates earlier. Patients have had restricted access to healthcare. Researchers
in many countries. This seems to be correlated with income. In partic­ have been prevented from working in their laboratories, as well as from
ular, the gap is much larger for middle-income countries than it is for their interactions with colleagues. Clinical studies have been delayed or
low- or high-income countries [28,36]. Specifically, the difference be­ even cancelled. The effects of all this remain to be determined.
tween the two genders in obesity prevalence rates in Tanzania, which is The experience from the last two years is expected to be decisive.
a middle-income country, is about 7% (6.7% the obesity prevalence for Recently, the WHO announced the global excess-deaths estimate for
males vs 13.1% for females) in 2019, while this difference was only 1.7% 2020 and 2021 due to COVID-19 (14.9 million) [47], which is compa­
in Japan and 1% in Bangladesh, which are countries with high and low rable to that of diabetes. For this reason, we should orient ourselves
income, respectively. For women, there is a non-linear relationship be­ again to the ongoing pandemic that we are battling—the obesity
tween obesity prevalence and income. This relationship is positive in pandemic which causes morbidity and mortality from diabetes, cardio­
low-income and negative in high-income countries. Nevertheless, male vascular diseases and other metabolic disorders, without losing focus on
obesity increases for all income levels, and although the curve plateaus, the COVID-19 pandemic which has subsided but continues to be with us.
there is no turning point. In high-income countries, this gender gap Undoubtedly, the golden key for combating the obesity pandemic, is
mitigates since the increase in female obesity is slower than that of male dual, first understanding its pathophysiology and then designing the
obesity. best prevention, education of the population and treatment approach.
Interestingly, the rate of BMI increase has been slowed down since No intervention would flourish if the patient continues a sedentary
2000 in high-income and some-middle income countries than the rates lifestyle and the adoption of a balanced dietary practice, such as the
of the previous century [24]. It is worth noting that the rise of obesity Mediterranean diet, which is reputed for its demonstrated preventive
prevalence rates has slowed down, especially during the past decade in effect of cardiovascular and metabolic disorders and obesity is of critical
the developed countries, such as the USA (from 30% in 2009 to 32% in importance [48]. There is also an urgent need for collaboration and
2019), UK (from 19% in 2009 to 19.7% in 2019) and France (from 13% communication between the government, public health authorities,
in 2009 to 14.5% in 2019). Nevertheless, the global obesity prevalence is community organizations, the food industry, physical therapists, di­
still rising, since in several, particularly developing regions with large etitians, clinicians, and schools to promote healthier eating habits and
populations the obesity trends have accelerated. For example, China, regular physical activity. Important first steps in this direction would be
which belongs to the countries with the largest population in the world educational programs and advertisements, restructuring urban and
[37], experienced a 90% increase in the prevalence of obesity in the last educational environments to facilitate physical activity, incentives for
decade (from 3.0% in 2009 to 5.7% in 2019). healthy living, as well as policy changes, such as taxes on sugar-
We would like to also emphasize the strong relationship between the sweetened beverages or mandatory standards for meals at schools. It is
two pandemics, the obesity and the COVID-19 pandemic, that coexist of great interest and encouragement that taxing sugar-sweetened bev­
and synergize, since it has repeatedly been shown after we first reported erages in Chile and Mexico led to a highly significant decrease in the
that, in a way, one exacerbates the other [38]. Several studies have purchase of this kind of drinks by 21.6% in Chile and 6.3% in Mexico
shown that patients with COVID-19 and obesity have increased risk for [49,50]. Additionally, the food industry should make efforts to reduce
severe disease, hospitalization, incubation, and death [38–43]. This is the fat, sugar, and salt content of processed foods, ensure the availability
not surprising since it has been described that obesity causes increased of affordable healthy food choices and limit the advertisement of foods
work of breathing by inducing the airway resistance and decreases high in sugar, salt, and fat especially those targeting the kids and teen
expiratory reserve volume, functional capacity, and pulmonary market [14].
compliance. Furthermore, obesity impedes diaphragmatic excursion in A stepwise approach to the obesity pandemic includes lifestyle
supine patients by compromising ventilation [44]. In addition, obesity is intervention with physical activity and diet [20,51] but this is generally
a chronic inflammatory condition with increased circulating levels of associated with moderate weight loss which is gradually regained, as
pro-inflammatory cytokines and COVID-19 builds upon that impaired well as pharmacotherapy, and the most efficacious method, bariatric
immune system to further exacerbate inflammation and lead to its surgery, which however costs more, is not really available to all, and
complications, morbidity and mortality [45]. According to the mortality may be accompanied by complications. In terms of pharmacotherapy, a
data examined by a team from Johns Hopkins University and the WHO special case of obesity derives from congenital or acquired leptin defi­
and released by the World Obesity Federation, global COVID-19 death ciency. Leptin is an adipokine which reflects the amount of energy
rates were more than 10 times higher in countries where more than half stored in the adipose tissue, acts centrally and decreases appetite. Thus it
the adults are overweight, compared to countries where fewer than half plays a key role in the pathogenesis of obesity. In this case, leptin
are overweight [46]. This report makes the correlation between obesity replacement ‘dramatically’ improves obesity and for this purpose the US
and mortality rates from COVID-19 clear and compelling and highlights Food and Drug Administration (FDA), the European Medicines Agency
the need for effective actions by individuals, the public, and govern­ (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency
ments to raise awareness of the risks flowing from obesity. (PMDA) approved metreleptin as a replacement therapy for leptin
To the relief of everyone, the negative impacts of the COVID-19 deficiency in patients with lipodystrophy as is provided to extremely
pandemic appear to be receding. It is too early to declare ‘the end of obese persons with congenital leptin deficiency on a compassionate

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C. Boutari and C.S. Mantzoros Metabolism 133 (2022) 155217

basis where it cannot be compensated [52]. Except that, at the end of and therapeutic tools that need to be safe, effective and affordable and
2020, the US FDA approved setmelanotide, a melanocortin 4 receptor we need better and broader implementation of novel therapies to make
agonist for use in individuals with severe obesity due to the rare genetic progress and thus help the obese live longer, happier and healthier lives.
leptin receptor deficiency [53]. Concerning pharmacotherapy for the
more conventional cases of obesity, glucagon-like peptide-1 (GLP-1)
analogs or receptor agonists play a role in regulating eating behavior by Declaration of competing interest
slowing gastric emptying, inducing postprandial satiety, and reducing
appetite and food consumption by acting on the hypothalamus, limbic Over the past 3 years, CSM has been a shareholder of and reports
reward system and cortex. Liraglutide and semaglutide have been sug­ grants through his institution from Merck, grants through his Institution
gested to be the most efficacious GLP-1 receptor agonists to induce and personal consulting fees from Coherus Inc. and AltrixBio, he reports
weight loss over at least 12 weeks of treatment (− 4.49 kg and − 9.88 kg, grants through his institution and personal consulting fees from Novo
respectively) [54]. Importantly, it has been demonstrated that the Nordisk, reports personal consulting fees and support with research re­
weight reducing effect of these agents is associated with changes in agents from Ansh Inc., reports personal consulting fees from Genfit,
regional fat stores while lean body mass is preserved resulting in a Lumos, Amgen, Corcept, Intercept, Astra Zeneca and Regeneron, reports
favorable effect on metabolic and cardiovascular risks of obesity [55]. support (educational activity meals at and through his institution) from
Thus, these agents currently appear as promising anti-obesity treatment Amarin, Novo Nordisk and travel support and fees from TMIOA, Elsev­
options. Recently, tirzepatide, a once weekly glucose-dependent insuli­ ier, College Internationale Researche Servier and the Cardio Metabolic
notropic polypeptide (GIP) receptor and GLP-1 receptor agonist that Health Conference. None is related to the work presented herein. C.S.M.
integrates the actions of both incretins into a single novel molecule, was also reports that in the past he was a shareholder of Pangea Inc., member
shown to achieve superior weight loss compared to placebo at 72 weeks of the California Walnut Commission Scientific Advisory Board and has
of treatment [56]. Specifically, 63% of participants taking a dose of 15 received travel and grant support by the California Walnut Commission,
mg lost at least 20% of their body weight. If there is inadequate response outside the submitted work. CB declares no conflicts of interest.
to initial therapy with a GLP-1 agonist or it is not tolerated, switching to
orlistat, a lipase inhibitor, is recommended. Phentermine, the most
widely prescribed weight loss drug in the USA, is only approved for the References
short-term treatment of obesity [57]. Additionally, existing anti-obesity
[1] Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D, et al. The
strategies we have recently reviewed extensively [58], other potential age-specific quantitative effects of metabolic risk factors on cardiovascular diseases
anti-obesity strategies are being explored, including novel drug delivery and diabetes: a pooled analysis. PLoS One 2013;8. https://doi.org/10.1371/
systems, vaccines, modulators of the gut microbiome, and gene therapy JOURNAL.PONE.0065174.
[2] Wormser D, Kaptoge S, Di Angelantonio E, Wood AM, Pennells L, Thompson A,
are currently under investigation. Undoubtedly, choosing a drug for et al. Separate and combined associations of body-mass index and abdominal
weight loss, which should definitely be safe and accessible, should be adiposity with cardiovascular disease: collaborative analysis of 58 prospective
individualized, shared decision-making process that accounts for pa­ studies. Lancet 2011;377:1085. https://doi.org/10.1016/S0140-6736(11)60105-0.
[3] Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body
tients' preferences, comorbidities, and out-of-pocket expenses, espe­ fatness and cancer — viewpoint of the IARC working group. N Engl J Med 2016;
cially during the economic downturn period following the pandemic. 375:794. https://doi.org/10.1056/NEJMSR1606602.
At Metabolism, the pandemic has been intellectually and physically [4] Barb D, Pazaitou-Panayiotou KMC. Adiponectin: a link between obesity and cancer.
Expert Opin Investig Drugs 2006;15:917–31. https://doi.org/10.1517/
demanding for the entire journal's personnel, who had all to preserve 13543784.15.8.917.
productivity beyond extraordinary personal and professional circum­ [5] Jiang L, Tian W, Wang Y, Rong J, Bao C, Liu Y, et al. Body mass index and sus­
stances in our everyday lives. Despite this and thanks to the magnificent ceptibility to knee osteoarthritis: a systematic review and meta-analysis. Jt Bone
Spine 2012;79:291–7. https://doi.org/10.1016/J.JBSPIN.2011.05.015.
efforts of everyone involved, the journal did not cease to deliver a high-
[6] Jiang L, Rong J, Wang Y, Hu F, Bao C, Li X, et al. The relationship between body
quality science, our metrics have continued to increase considerably (e. mass index and hip osteoarthritis: a systematic review and meta-analysis. Jt Bone
g. our cite score, i.e. our 4 year impact factor, has increased to 16.5 Spine 2011;78:150–5. https://doi.org/10.1016/J.JBSPIN.2010.04.011.
[7] Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in midlife and late-life
bringing us to the top 3% of Endocrinology and Diabetes journals) and
as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev 2011;
provides a notable platform for the outstanding research into obesity, 12. https://doi.org/10.1111/J.1467-789X.2010.00825.X.
diabetes and metabolism and their complications. [8] Alford S, Patel D, Perakakis N, Mantzoros CS. Obesity as a risk factor for Alz­
In the post-COVID-19 pandemic era it will be of utmost importance heimer's disease: weighing the evidence. Obes Rev 2018;19:269–80. https://doi.
org/10.1111/OBR.12629.
for all of us to learn from the COVID-19 pandemic, where collaborative [9] Vityala Y, Tagaev T, Zhumabekova A, Mamatov S. Evaluation of metabolic syn­
efforts worldwide have proven that science is capable of estimable drome, insulin secretion and insulin resistance in adolescents with overweight and
achievements. Obesity, diabetes and metabolism research and care de­ obesity. MetabClin Exp 2022;128:155011. https://doi.org/10.1016/J.
METABOL.2021.155011.
mand currently to be prioritized if we want to cast off the obesity [10] Morosanu A, Morosanu M. Relations between food intake, weight status and
pandemic. cardio-metabolic disturbances in area representative group. MetabClin Exp 2022;
In conclusion, the rise in obesity has accelerated in the last decade. 128:155022. https://doi.org/10.1016/J.METABOL.2021.155022.
[11] Andreyeva T, Sturm R, Ringel JS. Moderate and severe obesity have large differ­
Its prevalence is higher in females than males and increases with age. ences in health care costs. Obes Res 2004;12:1936–43. https://doi.org/10.1038/
Simultaneously, regional differences also exist. This obesity pandemic OBY.2004.243.
demands actions and interventions to reverse and address this problem. [12] Kjellberg J, Larsen AT, Ibsen R, Højgaard B. The socioeconomic burden of obesity.
Obes Facts 2017;10:493–502. https://doi.org/10.1159/000480404.
Prevention is the golden key in this direction and requires combined
[13] Woolcott OO, Seuring T. Prevalence trends in obesity defined by the relative fat
efforts from the governments, the scientific community, and the food mass (RFM) index among adults in the United States: 1999–2018. MetabClin Exp
industry to introduce the appropriate lifestyle modifications. 2022;128:155027. https://doi.org/10.1016/J.METABOL.2021.155027.
[14] Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obe
In this context, recently, on May 4, 2022, the President of the USA
sity-and-overweight. [Accessed 22 April 2022]. 2009.
Joe Biden announced a White House conference on hunger, nutrition, [15] Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C. Obesity as a disease. Med
and health to take place in September 2022 with a view to amplifying Clin North Am 2018;102:13–33. https://doi.org/10.1016/J.MCNA.2017.08.004.
and attenuating long-standing health inequities and disparities. This [16] Polyzos SA, Mantzoros CS. Obesity: seize the day, fight the fat. Metabolism 2019;
92:1–5. https://doi.org/10.1016/j.metabol.2018.12.011.
conference is expected to reflect evidence-based nutrition research and [17] Global Burden of Disease Study 2019 (GBD 2019). Covariates 1980-2019 | GHDx.
science, it should promote future research on nutrition science and focus n.d, https://ghdx.healthdata.org/record/global-burden-disease-study-2019-gbd-
on ensuring nutrition security and preventing and managing diet-related 2019-covariates-1980-2019. [Accessed 28 April 2022].
[18] Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe
diseases in the US and beyond. We need similar initiatives, ideally co­ obesity among adults: United States, 2017-2018 Key findings Data from the Na­
ordinated, worldwide, we need more research, we need new diagnostic tional Health and Nutrition Examination Survey. 2017.

6
C. Boutari and C.S. Mantzoros Metabolism 133 (2022) 155217

[19] DNPAO Data. Trends and maps: explore by topic | CDC. n.d, https://nccd.cdc.go [41] Qu HQ, Qu J, Glessner J, Hakonarson H. Mendelian randomization study of obesity
v/dnpao_dtm/rdPage.aspx?rdReport=DNPAO_DTM.ExploreByTopic&islClass=OW and type 2 diabetes in hospitalized COVID-19 patients. Metabolism 2022;129:
S&islTopic=&go=GO. [Accessed 2 May 2022]. 155156. https://doi.org/10.1016/J.METABOL.2022.155156/ATTACHMENT/
[20] Kluge HHP. Weltgesundheitsorganisation Regionalbüro für Europa. WHO Euro­ 701A9F6A-50CC-4E5D-9A8C-D42725EEF909/MMC5.PDF.
pean regional obesity report. 2022. n.d. [42] Sanoudou D, Hill MA, Belanger MJ, Arao K, Mantzoros CS. Editorial: obesity,
[21] Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism 2019;92: metabolic phenotypes and COVID-19. MetabClin Exp 2022;128:155121. https://
6–10. https://doi.org/10.1016/j.metabol.2018.09.005. doi.org/10.1016/J.METABOL.2021.155121.
[22] Toumba M, Fanis P, Vlachakis D, Neocleous V, Phylactou LA, Skordis N, et al. [43] Wang Y, Xu J, Wang Y, Hou H, Feng H, Yang H. An updated meta-analysis on the
Molecular modelling of novel ADCY3 variant predicts a molecular target for relationship between obesity and COVID-19 mortality. MetabClin Exp 2021;122:
tackling obesity. Int J Mol Med 2022;49. https://doi.org/10.3892/ 154820. https://doi.org/10.1016/J.METABOL.2021.154820.
IJMM.2021.5065. [44] Muscogiuri G, Pugliese G, Barrea L, Savastano S, Colao A. Commentary: obesity:
[23] Angelidi AM, Belanger MJ, Kokkinos A, Koliaki CC, Mantzoros CS. Novel non- the “Achilles heel” for COVID-19? Metabolism 2020;108:154251. https://doi.org/
invasive approaches to the treatment of obesity: from pharmacotherapy to gene 10.1016/J.METABOL.2020.154251.
therapy. Endocr Rev 2021. https://doi.org/10.1210/ENDREV/BNAB034. [45] Dietz W, Santos-Burgoa C. Obesity obesity and its implications for COVID-19
[24] NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, mortality. 2020. https://doi.org/10.1001/jama.2020.4683.
underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of [46] Obesity report: COVID-19 death rates 10 times higher in countries where most
2416 population-based measurement studies in 128⋅9 million children, adoles­ adults are overweight - CNN. n.d, https://edition.cnn.com/2021/03/04/health
cents, and adults. Lancet (London, England) 2017;390:2627–42. https://doi.org/ /obesity-covid-death-rate-intl/index.html. [Accessed 5 May 2022].
10.1016/S0140-6736(17)32129-3. 2009. [47] Global excess deaths associated with COVID-19, January 2020 - December 2021. n.
[25] Mathew H, Castracane VD, Mantzoros C. Adipose tissue and reproductive health. d, https://www.who.int/data/stories/global-excess-deaths-associated-with-covid-
Metabolism 2018;86:18–32. https://doi.org/10.1016/J.METABOL.2017.11.006. 19-january-2020-december-2021. [Accessed 10 May 2022].
[26] Wells JCK, Marphatia AA, Cole TJ, McCoy D. Associations of economic and gender [48] Angelidi AM, Kokkinos A, Katechaki E, Ros E, Mantzoros CS. Mediterranean diet as
inequality with global obesity prevalence: understanding the female excess. Soc Sci a nutritional approach for COVID-19. MetabClin Exp 2021;114:154407. https://
Med 2012;75:482–90. https://doi.org/10.1016/J.SOCSCIMED.2012.03.029. doi.org/10.1016/J.METABOL.2020.154407.
[27] Health effects of overweight and obesity in 195 countries over 25 years. N Engl J [49] Nakamura R, Mirelman AJ, Cuadrado C, Silva-Illanes N, Dunstan J, Suhrcke M.
Med 2017;377:13–27. https://doi.org/10.1056/NEJMOA1614362/SUPPL_FILE/ Evaluating the 2014 sugar-sweetened beverage tax in Chile: an observational study
NEJMOA1614362_DISCLOSURES.PDF. in urban areas. PLoS Med 2018;15:e1002596. https://doi.org/10.1371/JOURNAL.
[28] Ameye H, Swinnen J. Obesity, income and gender: the changing global relation­ PMED.1002596.
ship. Glob Food Sec 2019;23:267–81. https://doi.org/10.1016/J. [50] Colchero MA, Molina M, Guerrero-López CM. After Mexico implemented a tax,
GFS.2019.09.003. purchases of sugar-sweetened beverages decreased and water increased: difference
[29] Food supply - our world in data. n.d, https://ourworldindata.org/food-supply. by place of residence, household composition, and income level. J Nutr 2017;147:
[Accessed 3 May 2022]. 1552–7. https://doi.org/10.3945/JN.117.251892.
[30] Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol [51] Strategies to prevent & manage obesity | Overweight & Obesity | CDC. n.d, htt
2019;15:288–98. https://doi.org/10.1038/S41574-019-0176-8. ps://www.cdc.gov/obesity/strategies/index.html. [Accessed 6 May 2022].
[31] Wilkinson RG, Pickett K. The Spirit level: why more equal societies almost always [52] SA Polyzos CS. Mantzoros Metreleptin for the treatment of lipodystrophy: leading
do better. 2009. the way among novel therapeutics for this unmet clinical need n.d. doi:10.1080/
[32] Loomis WF. Why inequality is fatal. Nature 2009;4587242(458):1109–10. https:// 03007995.2022.2059974.
doi.org/10.1038/4581109a. 2009. [53] GSH Yeo, DHM Chao, Siegert AM, Koerperich ZM, Ericson MD, Simonds SE, et al.
[33] Nishida C, Barba C, Cavalli-Sforza T, Cutter J, Deurenberg P, Darnton-Hill I, et al. The melanocortin pathway and energy homeostasis: from discovery to obesity
Appropriate body-mass index for Asian populations and its implications for policy therapy. Mol Metab 2021;48. https://doi.org/10.1016/J.MOLMET.2021.101206.
and intervention strategies. Lancet (London, England) 2004;363:157–63. https:// [54] Vosoughi K, Atieh J, Khanna L, Khoshbin K, Prokop LJ, Davitkov P, et al. Associ­
doi.org/10.1016/S0140-6736(03)15268-3. ation of glucagon-like peptide 1 analogs and agonists administered for obesity with
[34] Seidell JC, Pérusse L, Després JP, Bouchard C. Waist and hip circumferences have weight loss and adverse events: a systematic review and network meta-analysis-
independent and opposite effects on cardiovascular disease risk factors: the Quebec NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). eClini­
Family Study. Am J Clin Nutr 2001;74:315–21. https://doi.org/10.1093/AJCN/ calMedicine 2021;42:101213. https://doi.org/10.1016/j.eclinm.2021.101213.
74.3.315. [55] Kadouh H, Chedid V, Halawi H, Burton DD, Clark MM, Khemani D, et al. GLP-1
[35] Lear SA, James PT, Ko GT, Kumanyika S. Appropriateness of waist circumference analog modulates appetite, taste preference, gut hormones, and regional body fat
and waist-to-hip ratio cutoffs for different ethnic groups. Eur J Clin Nutr 2010;641 stores in adults with obesity. J Clin Endocrinol Metab 2020;105. https://doi.org/
(64):42–61. https://doi.org/10.1038/ejcn.2009.70. 2009. 10.1210/CLINEM/DGZ140.
[36] Garawi F, Devries K, Thorogood N, Uauy R. Global differences between women and [56] Lilly's tirzepatide delivered up to 22.5% weight loss in adults with obesity or
men in the prevalence of obesity: is there an association with gender inequality? overweight in SURMOUNT-1 2022.
Eur J Clin Nutr 2014;6810(68):1101–6. https://doi.org/10.1038/ejcn.2014.86. [57] Pilitsi E, Farr OM, Polyzos SA, Perakakis N, Nolen-Doerr E, Papathanasiou AE, et al.
2014. Pharmacotherapy of obesity: available medications and drugs under investigation.
[37] Mi YJ, Zhang B, Wang HJ, Yan J, Han W, Zhao J, et al. Prevalence and secular MetabClin Exp 2019;92:170–92. https://doi.org/10.1016/J.
trends in obesity among Chinese adults, 1991–2011. Am J Prev Med 2015;49: METABOL.2018.10.010.
661–9. https://doi.org/10.1016/J.AMEPRE.2015.05.005. [58] Angelidi AM, Belanger MJ, Kokkinos A, Koliaki CC, Mantzoros CS. Novel non-
[38] Palaiodimos L, Kokkinidis DG, Li W, Karamanis D, Ognibene J, Arora S, et al. invasive approaches to the treatment of obesity: from pharmacotherapy to gene
Severe obesity, increasing age and male sex are independently associated with therapy. Endocr Rev 2021. https://doi.org/10.1210/ENDREV/BNAB034.
worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of pa­
tients with COVID-19 in the Bronx,New York. Metabolism 2020;108:154262.
https://doi.org/10.1016/J.METABOL.2020.154262. Chrysoula Boutari, Christos S. Mantzoros*
[39] Favre G, Legueult K, Pradier C, Raffaelli C, Ichai C, Iannelli A, et al. Visceral fat is Department of Medicine, Boston VA Healthcare system and Beth Israel
associated to the severity of COVID-19. Metabolism 2021;115:154440. https://doi. Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave,
org/10.1016/J.METABOL.2020.154440/ATTACHMENT/6E45EDD2-EB7F-4609-
A8BB-3F59D53FC351/MMC2.PDF.
Slosberg-Landay SL-419, Boston, MA 02215, USA
[40] Huang Y, Lu Y, Huang YM, Wang M, Ling W, Sui Y, et al. Obesity in patients with
COVID-19: a systematic review and meta-analysis. Metabolism 2020;113:154378. *
Corresponding author.
https://doi.org/10.1016/J.METABOL.2020.154378/ATTACHMENT/554D76D1-
70FA-4F5F-9AD1-CB630BDD72C5/MMC1.DOCX. E-mail address: [email protected] (C.S. Mantzoros).