Journal of Internal Medicine - 2024 - Sundbom - Obesity treatment in adolescents and adults in the era of personalized

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Review
doi: 10.1111/joim.13816
Obesity treatment in adolescents and adults in the era
of personalized medicine
Magnus Sundbom1,2, Kajsa Järvholm3,4, Lovisa Sjögren5,6 , Paulina Nowicka7 &
Ylva Trolle Lagerros8,9
From the 1Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; 2Department of Surgery, University Hospital, Uppsala,
Sweden; 3Department of Psychology, Lund University, Lund, Sweden; 4Childhood Obesity Unit, Skåne University Hospital, Malmö, Sweden;
5Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
6Department of Pediatrics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; 7Department of Food Studies,
Nutrition and Dietetics, Uppsala University, Uppsala, Sweden; 8Department of Medicine (Solna), Clinical Epidemiology Division, Karolinska
Institutet, Stockholm, Sweden; and 9Center for Obesity, Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden
Abstract. Sundbom M, Järvholm K, Sjögren L, Now-
icka P, Lagerros YT. Obesity treatment in ado-
lescents and adults in the era of personalized
medicine. J Intern Med. 2024;296:139–55.
In this multi-professional review, we will provide
the in-depth knowledge required to work in the
expanding field of obesity treatment. The preva-
lence of obesity has doubled in adults and quadru-
pled in children over the last three decades.
The most common treatment offered has been
lifestyle treatment, which has a modest or lit-
tle long-term effect. Recently, several new treat-
ment options—leading to improved weight loss—
have become available. However, long-term care
is not only about weight loss but also aims to
improve health and wellbeing overall. In the era
of personalized medicine, we have an obligation
to tailor the treatment in close dialogue with our
patients. The main focus of this review is new
pharmacological treatments andmodern metabolic
surgery, with practical guidance on what to con-
sider when selecting and guiding the patients
and what to include in the follow-up care. Fur-
thermore, we discuss common clinical challenges,
such as patients with concurrent eating disor-
der or mental health problems, and treatment
in the older adults. We also provide recommen-
dations on how to deal with obesity in a non-
stigmatizing way to diminish weight stigma dur-
ing treatment. Finally, we present six microcases—
obesity treatment for persons with neuropsy-
chiatric disorders and/or intellectual disability;
obesity treatment in the nonresponsive patient
who has “tried everything”; and hypoglycemia,
abdominal pain, and weight regain after metabolic
surgery—to highlight common problems in weight-
loss treatment and provide personalized treatment
suggestions.
Keywords: bariatric surgery, body mass index,
lifestyle, patient-centered care, pharmacotherapy,
weight loss
Introduction
One in eight people in the world lives with obesity,
that is, almost one billion people in 2022 [1]. From
1990 to 2022, the prevalence of obesity—defined by
a body mass index (BMI) of 30 kg/m2 or higher—
doubled in older adults and quadrupled in school-
aged children and adolescents [1]. Severe obesity
(BMI > 35 kg/m2) continues to increase, especially
in women [2].
Although obesity is not an immediate life-
threatening condition, it may affect quality of life
[3], reduce life expectancy, and result in comorbidi-
ties such as cardiovascular disease and type 2 dia-
betes [4]. Lifestyle treatment options have largely
been unsuccessful, leaving persons living with obe-
sity to a lifelong struggle. Lately, the advances in
basic science in pharmacotherapy have led to new
insights into the role of the brain for regulating
weight. Although genetic susceptibility differs, it is
well known that diet and physical activity influ-
ence energy balance, making those behaviors the
obvious target for lifestyle improvement. However,
hunger and reward often override the ability to
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Personalized obesity treatment / M. Sundbom et al.
Fig. 1 General factors influencing the choice of modern obesity treatment, that is, lifestyle modifications, pharmacotherapy,
and metabolic surgery in general, including long-term efficacy. The width of the bar indicates increased fulfillment of the
criterion. BMI, body mass index.
make the educated choices that could lead to sus-
tainable lifestyle change for persons affected by
obesity.
Obesity is a heterogeneous disease, and there
are no well-established predictors of response to
weight-loss interventions. A weight loss of >5% in
the first 3 months is currently our best predictor of
long-term weight loss [5, 6]. In the era of person-
alized care, the choice between fundamentally dif-
ferent interventions such as pharmacotherapy and
metabolic surgery should be based on individual
patient characteristics. Most patients will proba-
bly need several interventions or a combination of
interventions during his/her lifetime.
This multi-professional review on personalized
obesity treatment will present pros and cons as well
as risks with current weight-loss treatments, giving
practical tips in recommending the most suitable
method for long-term weight control in individual
patients. We will also present six microcases, fur-
ther discussing different solutions to various com-
mon problems in weight-loss treatment.
Treatment options
Treatment selection must be conducted in a care-
ful, personalized manner, preferably after evalua-
tion by multi-professional teams.
Although BMI is a blunt measure, especially in per-
sonalized medicine, BMI cannot be ruled out in the
decision-making process. Furthermore, most treat-
ment programs are BMI-based, even if cut-off levels
for different treatments may vary between coun-
tries and populations [7].
In general, BMI, severity and number of comor-
bidities, age, patient compliance, and risk of mal-
nutrition, together with overall efficacy, influence
the choice of treatment method in modern obesity
treatment Fig. 1.
Lifestyle treatment
Traditionally, the starting point for all obesity
treatment has been lifestyle treatment, aiming to
decrease energy intake and increase energy expen-
diture, resulting in a negative energy balance. In
broad terms, this requires modification of food
habits and physical activity, as also as attention
to other lifestyle aspects such as sleep and stress.
However, just providing simple advice such as
“eat more vegetables” and “exercise more” is not
effective and can even be counterproductive [8].
The most important factor for success is usually
a well-defined and structured program with close
follow-up.
Evidence-based healthy diet includes a vari-
ety of foods with daily servings of fruits and
140 © 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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Correspondence: Ylva Trolle Lagerros, Department of Medicine
Solna, Clinical Epidemiology Division, Karolinska Institutet,
Eugeniahemmet T2:02, Stockholm SE-171 76, Sweden.
Email: ylva.trolle@ki.se
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mailto:ylva.trolle@ki.se
	Obesity treatment in adolescents and adults in the era of personalized medicine
	 Introduction
	 Treatment options
	 Lifestyle treatment
	 Pharmacological treatment
	 Metabolic surgery
	 Practical advice for obtaining optimal results in obesity treatment
	 How to address obesity in a non-stigmatizing way
	 Obesity treatment in patients with eating disorder
	 Obesity treatment in patients with concurrent mental health disorders
	 Obesity treatment in older adults
	 Practical tips for successful pharmacological treatment
	 Choice of metabolic procedure
	 Microcases, highlighting different common problems in weight-loss treatment
	 Neuropsychiatric disorders and obesity treatment
	 Intellectual disability and obesity treatment
	 The non-responding patient who “has tried everything”
	 Hypoglycemia after gastric bypass surgery
	 Abdominal pain after metabolic surgery
	 Weight regain after metabolic surgery
	 Final comments
	 Author contributions
	 Conflict of interest statement
	 Funding information
	 Data availability statement
	Referencesspread throughout the day, and less energy-dense
foods such as low-fat alternatives and whole-grain
products, as well as choosing water instead of
sugar-sweetened drinks and fruit juices [9, 10].
To incrementally increase physical activity from
sedentary to any type of activity has beneficial
health effects, whereas highly intensive activities
are superior for cardiovascular health and weight
loss [11]. However, a person-centered approach is
fundamental in guiding toward realistic goals. A
subtle increase in daily activity can be a good start-
ing point for a healthy lifestyle for a person with
a moderately high BMI and a sedentary lifestyle,
although it might not lead to major weight loss.
Other psychosocial factors, such as stress and
mental health, need to be addressed because they
can influence the ability to achieve meaningful
changes in lifestyle. Because excessive alcohol use
can lead to weight gain [12], it needs to be han-
dled first. Pharmacotherapy for mood disorder,
sleep agents, insulin, systemic glucocorticoids,
and therapies for human immunodeficiency virus
can result in weight gain and alterations in the
metabolic profile [13]. A comprehensive review of
existing medications and collaboration with other
specialists to optimize the medication list—aiming
to minimize its potential to contribute to weight
gain—can be beneficial.
Additionally, support such as problem-solving
strategies, setting realistic sub-goals, identifying
obstacles and opportunities to overcome them, as
well as creating a plan and scheduling regular
follow-ups is often needed for successful weight
loss or weight loss maintenance [14]. At the same
time, it is important to have realistic expectations
of the effectiveness of lifestyle treatment. Behav-
ioral treatment can be successful if it begins early
in life, but the effect decreases with age [15]. Favor-
able long-term results from behavioral treatment in
adolescents are conspicuously absent. Overall, the
impact on weight loss based on changed lifestyle
behaviors is modest, also when implemented well.
In individuals with a genetic vulnerability to weight
gain, the normal trajectory is to gain weight.
For many people living with obesity, hunger is
the omnipresent component. This makes lifestyle
changes and weight maintenance a challenge.
Today, treatment options such as pharmacological
treatment and metabolic surgery, targeting hunger
and satiety, have led to new possibilities for per-
sonalized medicine. For that reason, we will pro-
vide an overview of these two options and present
recommendations of how they can be personalized.
Pharmacological treatment
The choice to initiate pharmacological treatment
is always based on clinical judgment. The guide-
lines issued by the American Association of Clin-
ical Endocrinologists and the American College of
Endocrinology [16] suggest initiating pharmacolog-
ical treatment as an adjunct to lifestyle treatment
in the following situations: (a) no weight-related
complication, but progressive weight gain; (b) mild
to moderate weight-related complications, where
lifestyle treatment did not give clinical improve-
ment on weight-related complications or when
there is weight regain after successful weight loss;
and (c) severe weight-related complications.
American Academy of Pediatrics clinical practice
guidelines state that adolescents from the age of 12
years should be offered pharmacological treatment
as an adjunct to lifestyle treatment [17]. Pharma-
cotherapy may be offered from the age of eight
under specific conditions [17].
A wide range of pharmacological treatment options
are available, with more on the way. This presenta-
tion will focus on treatment options that are avail-
able in most countries.
Orlistat. Orlistat, a gastric and pancreatic lipase
inhibitor, was introduced on the market in the
nineties. By inactivation of lipase, only 70% of
the ingested fat is absorbed [18], and the rest
is excreted as an oily diarrhea. After one year of
treatment with orlistat and a diet low in energy,
a weight reduction of 10.2%—that is, 4.1% more
than placebo and diet—can be expected in adults
[19]. However, based on clinical experience, well-
informed patients—using orlistat to detect fatty
products in daily life and avoiding or exchanging
them with low-fat alternatives—can have a three-
fold better effect than shown in studies.
Treatment duration of orlistat is unlimited. It can
also be used intermittently—for example, on week-
ends or as a safeguard to help keep to the low-
energy alternatives when energy-dense food can be
expected. Orlistat can also be used in combination
with other anti-obesity medications to enhance
weight loss or be used as support to maintain suc-
cessful weight loss.
© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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Naltrexone–bupropion. Naltrexone–bupropion
mediates its effect by affecting central appetite
control through the opioid receptor antagonist
naltrexone and by decreasing the reward-related
sensation of eating through the noradrenaline
reuptake inhibitor bupropion. Together, they mod-
ulate mood, appetite, and cravings. It has shown
a 6.1% weight reduction after 12 months of treat-
ment, 4.8% better than placebo [20]. Naltrexone–
bupropion can be an alternative when obesity is
coupled with pathological eating style, such as
binge eating, grazing, night-eating, hyperphagia,
sweet eating, and cravings for carbohydrates [21].
Phentermine–topiramate. Phentermine–topiramate
has shown a 10.9% weight reduction, that is, 9.3%
better weight loss than placebo after 12 months
of treatment [22]. Phentermine hydrochloride was
approved by the FDA already in 1959. It stimulates
the hypothalamic release of norepinephrine, which
affects the central control of appetite. Topiramate,
used for treatment of epilepsy and prevention of
migraine, has also been shown to produce weight
loss. Animal experiments suggest that the mech-
anisms are decreased energy intake, increased
energy expenditure, and decreased energetic
efficiency [23]. It can be used from 16 years of age.
GLP-1 and GIP receptor agonists. Glucagon-like
peptide-1 (GLP-1) is an incretin hormone released
from the enteroendocrine cells in the gut as a
response to food intake [24]. GLP-1 receptor ago-
nists mimic this effect in two different pathways.
The central effect is increased sensation of satiety
and reduced hunger, whereas the peripheral effect
contributes to a slower gastrointestinal transit,
decreased blood pressure, and increased insulin
secretion. GLP-1 receptor agonists are currently
available as daily (liraglutide) or weekly (semaglu-
tide) subcutaneous injections and are approved
from 12 years of age.
In adults, an 8%-weight loss can be expected from
liraglutide treatment lasting 12 months, 5.4% bet-
ter than placebo [25], while adolescents during a
56-week trial had a mean weight loss of 3.3%.
Adolescents randomized to placebo increased their
weight by 2.2% during the same time [26].
Semaglutide has demonstrated a 15.5%-weight
loss in adolescents and a 12.5%-weight reduc-
tion in adults after 68 weeks of treatment [27,
28]. Both substances have cardiovascular benefi-
ciary effects [29, 30]. Semaglutide reduced the risk
of cardiovascular events in a large population of
patients with obesity without type 2 diabetes [30]
and reduced symptoms in patients with heart fail-
ure while achieving weight loss [31]. Persons with
type 2 diabetes, prediabetes,metabolic syndrome,
a potential risk of future cardiovascular events, or
a low grade of satiety following a meal should be
prioritized for GLP-1 receptor agonists.
Low levels of GLP-1 after metabolic surgery are a
biological driver that seems associated with poor
weight loss and weight regain after surgery. Adju-
vant treatment with GLP-1 analogues can give back
the sense of being newly operated and has been
shown to give clinically effective weight loss in
patients with meager surgical weight loss [32, 33].
Tirzepatide is a dual GLP-1 and glucose-dependent
insulinotropic peptide (GIP) receptor agonist.
Although GIP has several peripheral effects, the
central effect on energy intake is thought to be
of greatest importance [34]. Weekly injections of
tirzepatide resulted in a 20.9% weight reduction
compared to 3.2% for the placebo group after 72
weeks [35].
Treatment options in monogenetic obesity. Two
new treatment options have emerged for patients
with monogenetic causes of obesity, with uncon-
trolled hyperphagia and early onset of severe obe-
sity [36, 37]. First, metreleptin—a recombinant
leptin analog—is a treatment option for patients
with congenital leptin deficiency. It normalizes
weight and appetite [37]. Second, setmelanotide—
a peptide agonist of the melanocortin 4 recep-
tor (MC4R)—can be used in patients with genetic
variants of the MC4R receptor. By affecting the
MC4R pathway, a normalized appetite function is
attained [38].
What to expect from pharmacological treat-
ment. At 1 year, a total weight loss of 5% to >20%
can be expected from pharmacological treatment,
depending on pharmacological substance, inten-
sity of lifestyle modification, and degree of support.
In an attempt to enhance response to obesity
pharmacotherapy, Acosta et al. conducted a
pragmatic clinical trial and stratified 84 persons
attending care at an obesity clinic into different
phenotypes [39]. Persons classified as having a
hungry gut (reduced duration of fullness) received
GLP-1 analogues, those classified as having
a hungry brain (abnormal satiation) received
phentermine–topiramate, those with emotional
142 © 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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iley O
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ibrary on [02/01/2025]. See the T
erm
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onditions (https://onlinelibrary.w
iley.com
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ibrary for rules of use; O
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reative C
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icense
Personalized obesity treatment / M. Sundbom et al.
Fig. 2 General factors influencing the choice of pharmacological therapy, that is, orlistat, naltrexone/bupropion,
phentermine–topiramate, and glucagon-like peptide-1 (GLP-1) analogues, with or without glucose-dependent insulinotropic
peptide (GIP) analogues, including long-term efficacy. The width of the bar indicates increased fulfillment of the criterion.
BMI, body mass index; MAFLD, metabolic dysfunction-associated fatty liver disease.
hunger (emotional eating, cravings, and reward-
seeking) received naltrexone–bupropion and
those with low predicted energy expenditure—
labeled slow burn—received phentermine and
were advised to engage in resistance training. The
authors concluded that weight loss was 1.75-fold
greater (in total 15.9%) in the phenotype-guided
treatment group after 12 months, compared to
patients for which phenotype did not guide the
decision.
Anti-obesity medication is currently prescribed
based on comorbidities, risk profile, preferences,
and economy (or insurance coverage). However,
further studies on personal factors such as biol-
ogy, behavior, psychosocial situation, and envi-
ronment are needed to enhance our under-
standing of personalized medicine and how to
improve clinical outcomes of pharmacological
treatment.
Suitable patients. Persons with BMI ≥ 30 kg/m2,
or for adults, a BMI ≥27 kg/m2 with ≥1 comor-
bidity, can be offered pharmacological treatment.
Specific comorbidities influence the choice of phar-
macological treatment. The recommendations are
summarized in Fig. 2.
Metabolic surgery
The metabolic procedures performed today are
the result of continuous improvements over many
decades. Herein, we focus on the two most
common procedures—gastric bypass and sleeve
gastrectomy—and a highly effective malabsorptive
procedure, duodenal switch. As the type of proce-
dure fundamentally changes eating behavior and
daily life, the patient’s opinion regarding the choice
of surgical method is especially important. In con-
trast to pharmacological treatment, discontinua-
tion or switching to another surgical treatment is
difficult, or sometimes even impossible.
Today, almost all procedures are performed by
laparoscopic technique—that is, minimally inva-
sive surgery. This technical revolution has resulted
in reduced postoperative pain, faster recovery, and
fewer complications than open surgery [40].
This, in combination with the superior effects on
obesity-related diseases, has resulted in a tenfold
increase of metabolic surgery since the turn of the
millennium [41, 42]. Despite this, only about 1% of
eligible patients receive surgical treatment, even in
countries with the highest operative rate [41]. Fur-
thermore, health-related quality of life—measured
by various questionnaires—demonstrates large
improvements after surgery, especially in physical
domains [43].
There are systematic reports of improved mental
health short-term after surgery, but when patients
are followed long-term, mental health problems
seem to return to baseline [44]. An increased
risk of developing substance use disorder—mainly
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iley.com
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Personalized obesity treatment / M. Sundbom et al.
alcohol [45], due to altered uptake and metabolism
[46, 47]—has been described.
In 2022, the American Society for Metabolic and
Bariatric Surgery (ASMBS) and International Fed-
eration for the Surgery of Obesity and Metabolic
Disorders (IFSO) updated the guidelines and now
recommend metabolic surgery for individuals with
a BMI≥ 35 kg/m2, regardless of presence, absence,
or severity of concomitant obesity-related dis-
ease. According to the new recommendations,
surgery should also be considered for individ-
uals with metabolic disease and BMI of 30–
34.9 kg/m2. In the Asian population, BMI thresh-
olds should be adjusted such that individuals with
BMI ≥ 27.5 kg/m2 ought to be offered surgery.
Finally, selected children and adolescents should
be considered for metabolic surgery—for example,
when BMI is above 120% of the 95th percentile and
there is comorbidity, or when BMI is above 140%
of the 95th percentile [48].
Gastric bypass. In gastric bypass, ingested food
is prevented from entering the stomach. This is
done by redirecting the passage of food into the
small intestine directly after passing a small gastric
pouch, just below the esophagus. Initially, reduced
food intake was thought to be the sole working
mechanism, but in time, the vast changes in var-
ious gastrointestinal hormones—triggered by the
rapid emptying into the small bowel—have become
evident. The changes in GLP-1 and GIP decrease
hunger, whereas increased levels of incretins result
in improvement of type 2 diabetes, even before any
substantialweight loss occurs.
What to expect from gastric bypass. Gastric
bypass results in large and long-lasting weight
loss. Maximum weight loss is achieved at 2 years
(30%–35% reduction of total body weight), and at
12–15 years postoperatively, a 25%–27% total body
weight loss remains [49, 50]. The procedure leads
to long-term remission of obesity-associated condi-
tions such as type 2 diabetes, dyslipidemia, hyper-
tension, and sleep apnea [51]. Furthermore, the
rate of new onset obesity-related diseases is low
[52]. Gastric bypass is also known to relieve gas-
troesophageal reflux [53]. In adolescents, general
health and physical functioning increased follow-
ing gastric bypass [54].
On the downside, dumping syndrome may occur
if a meal contains a high level of sugar or fat,
probably due to osmotic disturbances in the prox-
imal small bowel. In addition, to avoid micro and
macronutrient deficiencies, the patient needs to
be on lifelong vitamin and mineral supplemen-
tation. In a recent meta-analysis, 23% of gastric
bypass patients were found to have iron deficiency
at 10 years [55], a condition often resulting in
anemia. Furthermore, drugs with a narrow ther-
apeutic window—for example, lithium and some
antiepileptics—can be difficult to dose. Stomal
ulcers and small bowel obstruction—either due
to kinking or internal herniation behind one of
the two anastomoses—occur in about 5% of all
patients [56].
Suitable patients. According to our opinion, gas-
tric bypass is suitable for patients with BMI 35–
50 kg/m2, especially those having type 2 diabetes
and other obesity-related comorbidities, and for
patients with reflux.
Patient groups less suitable for gastric bypass
include those with chronic abdominal pain, those
at increased risk of alcohol or substance abuse,
and those with inflammatory bowel disease.
Sleeve gastrectomy. In sleeve gastrectomy, a
major part of the stomach is removed, leaving a
narrow passage—a “sleeve”—along the lesser cur-
vature. The rather simple nature of the operation
has made it popular. It can also be performed as
a first step for patients with severe obesity and
rather easily be converted into other procedures
such as gastric bypass and duodenal switch. How-
ever, sleeve gastrectomy is a truly nonreversible
procedure.
What to expect from sleeve gastrectomy. Ini-
tial weight loss is similar to gastric bypass, but in
the long-term many will regain weight [57]. Thus,
sleeve gastrectomy is considered less effective than
gastric bypass. Additionally, it has lower remission
rate of obesity-related diseases [57].
Notably, sleeve gastrectomy is prone to induce or
worsen reflux, which is a risk factor for esophageal
cancer. It has been shown that the use of continu-
ous proton pump inhibitors more than triples, from
5.2% before surgery to 16.4% 5 years postopera-
tively [53].
Suitable patients. According to our opinion, sleeve
gastrectomy can be suitable for patients with BMI
30–40 kg/m2, especially in those with an expected
need for future access to the biliary tree, chronic
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iley O
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onditions (https://onlinelibrary.w
iley.com
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ibrary for rules of use; O
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icense
Personalized obesity treatment / M. Sundbom et al.
Fig. 3 General factors influencing the choice of metabolic procedures, that is, gastric bypass, sleeve gastrectomy, and
duodenal switch, including long-term efficacy. The width of the bar indicates increased fulfillment of the criterion. BMI,
body mass index.
abdominal pain, or inflammatory bowel disease
[58, 59].
Less suitable patients include those with reflux,
type 2 diabetes, and other severe comorbidities, or
those with a need for large weight loss.
Biliopancreatic diversion with duodenal switch.
In duodenal switch, the sleeve-shaped stomach
pouch empties directly into the distal part of the
small bowel, thus shortening the passage. The pro-
cedure leads to reduced food intake by the sleeve
component and reduced absorption of fat-soluble
nutrients by the jejunal exclusion.
What to expect from duodenal switch. Duodenal
switch has shown a total weight loss of 38.6% at 15
years of follow-up [60] and good effect on obesity-
related diseases, such as type 2 diabetes [61].
The disadvantages include diarrhea and smelly
stools due to undegraded fat. In a study of
bowel habits, duodenal switch-operated patients
needed to empty their bowel at least twice daily
and reported an increased need for keeping a
strict diet [53]. The malabsorption also induces
a large risk for vitamin and micronutrient defi-
ciencies, as well as hypoproteinaemia, sometimes
resulting in edema in the lower part of the
body.
Suitable patients. Duodenal switch and other
malabsorptive procedures are suitable for patients
with BMI > 50 kg/m2, especially those having dia-
betes type 2 or other severe obesity-related dis-
eases.
Less suitable patients include those with inflam-
matory bowel disease or frequent loose stools, and
those with lower likelihood of participating in a
close follow-up regime. Postoperative vitamin and
mineral supplementation should be carefully mon-
itored by experienced specialists.
As demonstrated in Fig. 3, the three discussed
metabolic procedures have their special profiles,
making gastric bypass most suitable in those hav-
ing type 2 diabetes or higher BMIs (35–50 kg/m2),
whereas duodenal switch can be recommended in
patients with more severe obesity (BMI >50 kg/m2)
who are able to participate in a close follow-up.
Although sleeve gastrectomy lacks long-term
data, the procedure can be used for patients with
moderate BMIs (30–35 kg/m2), preferably free of
diabetes, or the ambition to maintain normal BMI
in the long term.
Short summary of potential treatment options, with
focus on pharmacological treatment and metabolic
surgery. Individuals with a BMI ≥ 27 kg/m2 can
be offered pharmacological treatment, whereas
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Personalized obesity treatment / M. Sundbom et al.
those with a BMI ≥ 30 kg/m2 may be surgical
candidates. Individuals with a very high BMI
should be offered surgery, independent of prior
treatment. Irrespective of therapy chosen, lifestyle
changes are important for long-term weight loss
maintenance. A short summary of pros and cons
with pharmacological treatment and metabolic
surgery is given in Table 1.
Practical advice for obtaining optimal results in obesity
treatment
How to address obesity in a non-stigmatizing way
A significant barrier in obesity treatment is weight
stigma. For example, according to a Canadian
study, 18.5% of family physicians expressed feel-
ings of disgust while attending to patients with
obesity [62]. Stigmatizing attitudes impact patients
with obesity and lead to increased stress, reluc-
tance to seek treatment, lack of trust in medical
professionals, and diminished expectations of
treatment [63].
To address and diminish weight bias and obesity
stigma:*
• Begin by seeking permission to discuss weight.
• Use people-first language—that is, talkabout
the disease as something the patient has (obe-
sity) and not as something the patient is (obese).
• Make sure that the clinic is equipped to be
inclusive of people with higher weights. Are
there chairs without armrests and large blood
pressure cuffs? Can the scales measure weights
above 250 kg/550 lbs? Can weight be measured
in private?
• Conduct a respectful weight assessment.
• Assist the patient in comprehending the compli-
cated nature of obesity, the impact of the cur-
rent obesogenic environment, and acknowledge
the genetic inheritance.
• Undertake a thorough medical evaluation,
encompassing both physical and psychological
aspects and offer regular reassessments.
• Do not assume that you know anything about
a patient’s lifestyle and habits based on his or
her weight.
• Assess food habits, physical activity, and other
lifestyle factors as neutrally as possible.
• Ask the patient about previous weight-loss
attempts and obesity treatments. What has and
has not been helpful in the past?
• Inquire sensitively about any past experiences
of stigma.
• Provide the patient with an overview of offi-
cial recommendations for obesity care. Involve
the patient in developing a personalized and
sustainable care plan. Avoid oversimplified
solutions such as presuming that minor
daily changes in diet and physical activity
suffice.
• Facilitate collaboration with other professionals
as needed.
• Avoid assuming that if weight remains
unchanged, behaviors have also stayed the
same.
*Adapted from the recommendations for pediatri-
cians on how to tackle weight stigma in children
by Tanas et al. [64] and the joint consensus state-
ment about the importance of language for health
care professionals by Albury et al. [65].
Obesity treatment in patients with eating disorder
Eating disorders are more prevalent in people liv-
ing with obesity, yet often undiagnosed [66]. Binge
eating disorder is the most common eating dis-
order in people with obesity. Still, it is important
to acknowledge that most people with obesity do
not fulfill the criteria for an eating disorder [66].
Clinicians should ask patients seeking weight-loss
treatment whether they experience loss of con-
trol while eating. Patients who present with an
eating disorder should be referred to such treat-
ment. However, it is important to inform patients
that treatment for binge eating disorder normally
leads to weight stabilization rather than weight
loss [67].
A common concern among both patients and care-
givers is that obesity treatment could trigger an
eating disorder. However, available evidence con-
tradicts such a notion [68]. Instead, all forms
of professional obesity treatment seem to reduce
eating disorder symptoms. Reduced symptoms of
eating disorders have been seen after metabolic
surgery [69].
Obesity treatment in patients with concurrent mental
health disorders
Patients with manifest mental health disorders
are often excluded from clinical trials, leav-
ing little guidance on obesity treatment for this
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iley O
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erm
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onditions (https://onlinelibrary.w
iley.com
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ibrary for rules of use; O
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icense
Personalized obesity treatment / M. Sundbom et al.
Ta
bl
e
1.
Su
m
m
ar
y
of
co
m
m
on
ph
ar
m
ac
ol
og
ic
al
an
d
su
rg
ic
al
tr
ea
tm
en
to
pt
io
ns
fo
r
ob
es
ity
.
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ar
m
ac
ol
og
ic
al
tr
ea
tm
en
t
M
et
ab
ol
ic
su
rg
er
y
O
rl
is
ta
t
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al
tr
ex
on
e
+
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pr
op
io
n
Ph
en
te
rm
in
e
+
to
pi
ra
m
at
e
Li
ra
gl
u
ti
de
S
em
ag
lu
ti
de
Ti
rz
ep
at
id
e
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as
tr
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by
pa
ss
S
le
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ga
st
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ct
om
y
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u
od
en
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it
ch
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pe
of
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te
rv
en
ti
on
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ac
ti
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e
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en
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xc
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© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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iley O
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iley.com
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iley O
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A
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reative C
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m
ons L
icense
Personalized obesity treatment / M. Sundbom et al.
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148 © 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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erm
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onditions (https://onlinelibrary.w
iley.com
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Personalized obesity treatment / M. Sundbom et al.
group of patients. A common side effect of psy-
chotropic medications is increased hunger, which
leads to overeating and significant weight gain
[70]. Concurrent metformin treatment can, for
some, alleviate the weight increase, whereas GLP-
1 analogues—which do not interfere with psy-
chotropic drugs—are better for weight loss.
Metabolic surgery can be an option, provided that
the patient receives careful postoperative monitor-
ing for any psychiatric decline. A meta-analysis of
more than 32,000 patients indicated a postsurgi-
cal reduction in depressive symptom scores after
24 months, irrespective of surgical procedure [71].
However, self-harm and depression prior to surgery
seem to be risk factors for subsequent readmission
to psychiatric care [72].
Obesity treatment in older adults
The older the patient, the more important it is
to make an individual risk-benefit assessment
before weight-loss treatment begins. Multimorbid-
ity, polypharmacy, and frailty must be considered,
whereas health-related goals rather than weight
should guide the decisions. As with the young,
weight loss in older patients will lead to improved
cardiovascular risk factors, better physical func-
tion, fewer symptoms of pain, remission of comor-
bid disease, better regulation of diabetes, and
reduced markers of inflammation, but there is lim-
ited data on the effect of weight loss on risk for CVD
and longevity [73]. Similarly, there is limited data
on the effect of weight-loss medications in older
adults.
The weight loss trajectory is not the same in older
adults compared to younger counterparts. It is
more challenging to lose weight in older age than
in younger age. Preserving lean and bone mass
is essential independent of choice of treatment
because lean body mass accretion is decreased
while fat accretion is increased. Weight regain after
weight loss may thus be particularly problematic
as it does not restore lost lean mass or bone follow-
ing weight loss [74]. In older adults, weight regain
might thus increase the risk of sarcopenic and/or
osteopenic obesity and should be avoided.
Nonetheless, the 2022 international consensus
statement for metabolic surgery points out that
there is no evidence to support an upper age limit
for surgery. Frailty rather than age alone is associ-
ated with postoperative complications [48].
Practical tips for successful pharmacological treatment
There is heterogeneity in the inter-individual
response to different treatment options. Con-
trary to pharmacological treatment of diabetes, for
example, there is a lack of a target laboratory value
in obesity treatment. Lowest possible effective dose
leading to weight loss is desirable and will lead to
fewer side effects. Side effects, high cost, and con-
sequently low compliance may be the price of a fast
titration to maximal dosage. Instead of a set sched-
ule for titration, titration can be conducted by the
informed patient, who increases the dose in rela-
tion to the effect on appetite. This leads to a suit-
able dosage with tolerable side effects and possi-
bly improved compliance. It can be wise to prolong
certain dosage steps until side effects subside or to
decrease the dosage to the previous dose if intol-
erable side effects occur. Because many patients
experience an adaptation—with a lower effect of
anti-obesity medication over time and an increased
desire to eat [75]—the possibility to increase the
dosage at a later treatment stage can be useful. Yet,
those that have reached target weight may require
a lowered dose for weight maintenance.
Timing of medication over the day should be eval-
uated to better respond to certain eating habits
or cravings. Side effects and treatment outcomes
ought to be assessed regularly. If the patient is
weight stable after the first 12 weeks of treat-
ment, other treatment options should be evalu-
ated. Extra psychosocial support may be needed
if the treatment has failed the patient, as self-
confidence to lose weight might be low. Failing
pharmacotherapy or other non-surgical therapies
does not exclude metabolic surgery but instead
strengthens the indication.
Medication discontinuation. Medication discontin-
uation can be done without tapering. The patient
should be informed of the high risk of weight regain
[76]. Regular meetings with a dietician and/or
intermittent pharmacological treatment could be
strategies to minimize the risks for weight regain.
Periodic pharmacological treatment may also be a
way to meet high costs, restricted drug availability,
and life events leading to loss of control overeating.
Pharmacological treatment can also be used for
weight control after successful weight loss [77].
Obesity should be seen as a chronic disease. Con-
tinued treatment is usually required to gain long-
term benefits, independent of whether treatment is
lifestyle, pharmacotherapy, or surgery.
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Choice of metabolic procedure
The surgeon—more than choice of hospital or indi-
vidual patient factor—influences the decision of
type of surgical procedure the most [78]. However,
as metabolic surgery results in life-long changes
in gastrointestinal physiology, it is important to
inform the patients about pros and cons related
to the most common procedures. The choice of
surgery should be based on patient factors such as
BMI and comorbidities such as gastroesophageal
reflux disease and type 2 diabetes, as well as over-
all goals. Presenting and interpreting data already
at referral assists the patient in making an edu-
cated choice, which may diminish the risk of future
problems.
Microcases, highlighting different common problems in
weight-loss treatment
In the following six microcases, we suggest solu-
tions to various common problems in weight-loss
treatment. The discussion is based on the litera-
ture as well as clinically proven experience.
Neuropsychiatric disorders and obesity treatment
Problem: Patient with obesity and suspected
attention-deficit/hyper-activity disorder (ADHD).
Comment: Patients with neurodevelopmental dis-
order such as ADHD are overrepresented within
the group in need of obesity treatment [79, 80].
Neuropsychiatric disorders should not be seen as
a contraindication for weight-loss treatment [48].
Evaluated, treated, and stable patients with neu-
ropsychiatric disease should be offered pharma-
cological treatment or metabolic surgery in rou-
tine care. Since impaired executive functions are
common, the task of booking one´s own follow-up
appointment can be overwhelming. Special atten-
tion may be needed to retain the patients. For
example, this patient group attends postoperative
follow-up to a lower degree than patients without
ADHD [81].
Suggested treatment: If neuropsychiatric disease
is suspected, prioritize conducting a neuropsy-
chiatric evaluation. Treatment with stimulants
(methylphenidate) suppresses appetite, counter-
acts reward dependency, and improves execu-
tive functions, thereby enabling significant weight
loss. Keep in mind that some patients on short-
acting agents report loss of control and overeat-
ing when the effect diminishes after 8 hours. Tar-
geted strategies to improve clinic attendance may
be needed.
Intellectual disability and obesity treatment
Problem: Patient with intellectual disability in need
of help from caregivers for daily living.
Comment: Obesity is overrepresented in patients
with neurodevelopmental disorders [82] and/or
intellectual disability [83].
Suggested treatment: Lifestyle treatment may need
to be targeted toward caregivers and family in a
team-based fashion to be effective. Pharmacologi-
cal treatment can be recommended and will prob-
ably have an even larger indication in the future.
However, metabolic surgery should only be per-
formed in selected cases.
The non-responding patient who “has tried everything”
Problem: Patient has “tried everything,” including
available pharmacological treatment with some
weight loss but with no long-term effect. Alterna-
tively, the patient says that he/she “eats nothing”
and still does not lose weight.
Comment: This is common and frustrating for the
individual.
Suggested treatment: A detailed weight anam-
nesis may elucidate fundamental reasons for
weight loss failure. Lifestyle circumstances such
as stress, sleep disorder and other health issues,
family distress, and economical difficulties could
disturb the hard work of weight loss. Binge eat-
ing, a high alcohol intake, irregular or night eat-
ing, or weight-inducing pharmacological treat-
ment may be a consequence of the compli-
cated life situation, which further drives obesity.
This must be handled first. Thereafter, struc-
tured, intensified treatment guided by profes-
sionals specialized in weight-loss treatment could
be tried. Metabolic surgery should be discussed
when the patient has repeatedly experienced
weight loss and weight regain—also called “yo-yo
dieting”—because surgery usually leads to sus-
tained weight loss.
Hypoglycemia after gastric bypass surgery
Problem: Gastric bypass patient with good weight
loss, but has recurrent episodes of late hypo-
glycemia occurring several hours after meals.
Comment: Dumping syndrome—including nausea
and feeling light-headed or tired after a meal—is
caused by rapid gastric emptying. This is rather
common after gastric bypass but usually sub-
sides with time. Some patients experience hypo-
glycemia due to an insulin overshoot one to 3
hours after a meal. Hypoglycemia should be ver-
ified by continuous glucose monitoring before
treatment.
150 © 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
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iley O
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iley.com
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icense
Personalized obesity treatment / M. Sundbom et al.
Suggested treatment: Hypoglycemia is usually
treated with dietary adjustments. Acarbose—
which delays carbohydrate absorption, or
octreotide—a synthetic form of somatostatin—
can be used. Sometimes GLP-1 analogues are
useful. Surgery to restore the original anatomy
may be a last resort.
Abdominal pain after metabolic surgery
Problem: Abdominal pain in patients having had
metabolic surgery.
Comment: Patients having had metabolic surgery
should be free of abdominal pain. Hence, this
warrants further investigation.
Suggested treatment: As in all patients, a rou-
tine physical examination—including laboratory
tests—should be performed. In patients with epi-
gastric pain, an endoscopy should be performed
to rule out reflux esophagitis and ulcers. Gastric
bypass or duodenal switch patients with meal-
associated colicky pain must be evaluated by
computed tomography to exclude internal hernia,
an entrapment of the small bowel behind one of
the anastomoses. If present, this condition can
be corrected by a laparoscopic procedure. Biliary
colic due to gallbladder stones, often developing
during rapid weight loss, can cause similar pain
and should be evaluated by ultrasound. Diffuse
pain or pain that occurs irrespective of meals or
time of the day is often very difficult to diagnose
and treat. Restoring the original anatomy is often
fruitless.
Weight regain after metabolic surgery
Problem: Initially good response to metabolic
surgery. Thereafter, substantial weight regain.
Comment: A slight weight regain between 2 and
6 years is common after metabolic surgery and
is sometimes considered to be a physiological
defense mechanism to weight loss [84, 85]. How-
ever, over time, most patients maintain around
25% total weight loss [50].
Suggested treatment: Technical defects—such as
gastro-gastric fistula in gastric bypass and
remaining fundus or a wide sleeve in sleeve
gastrectomy—should be ruled out and corrected.
If none exist, adjunct pharmacological treat-
ment is recommended [84]. First-line treatment
is GLP-1 analogues given in normal to high
doses in conjunction with dietary counseling
[86]. In an American study of 59,160 adults
with prior bariatric surgery, about 13% of the
patients had anti-obesity drugs postoperatively—
that is, topiramate (8%), liraglutide (3%), phen-
termine/topiramate(1%), naltrexone/bupropion
(1%), semaglutide (0.5%), and orlistat (0.2%). The
authors concluded that despite weight regain
being relatively common, anti-obesity drugs are
underutilized after bariatric surgery [87].
Next, conversion of an unsuccessful sleeve gas-
trectomy into gastric bypass can be efficient. This
correcting procedure results in additional weight
loss, although less than in a primary gastric bypass
[88]. Patients with poor weight loss following gas-
tric bypass can be converted into duodenal switch,
which is a technically demanding procedure only
conducted in specialized centers.
Final comments
The treatment arsenal for obesity has never been
more diverse than now, and more treatment
options are on the way. Thus, parts of this review
may not be up-to-date in the near future, although
the basic mechanisms remain relevant. However,
most importantly, the variety of treatment modali-
ties will give the opportunity to tailor the treatment
with a combination of different components pro-
vided in sequence or together. We need to listen to
our patients and talk with our colleagues across
professions, disciplines, and geographical borders.
With time, individual variability in genetics, intesti-
nal microbiome, and metabolites will further guide
us to understand and improve the treatment of
obesity. The era of personalized obesity treatment
has just begun.
Author contributions
Magnus Sundbom: Writing—original draft; visu-
alization; writing—review and editing; concep-
tualization. Kajsa Järvholm, Lovisa Sjögren,
and Paulina Nowicka: Writing—original draft;
writing—review and editing; conceptualization.
Ylva Trolle Lagerros: Writing—original draft;
writing—review and editing; project administra-
tion; conceptualization.
Conflict of interest statement
Expert committee for the Swedish national guide-
lines for obesity care: all authors. Board members
of the Swedish organization for obesity research:
KJ, LS, and YTL, the Swedish organization for
childhood obesity: KJ, the Swedish pediatric
© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
Journal of Internal Medicine, 2024, 296; 139–155
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iley O
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erm
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onditions (https://onlinelibrary.w
iley.com
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s-and-conditions) on W
iley O
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ibrary for rules of use; O
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icense
Personalized obesity treatment / M. Sundbom et al.
treatment registry: LS, the Scandinavian Obesity
Surgery Registry: MS. Local principal investigator
in a global phase III study of a GLP-1/glucagon
dual agonist for adults: YTL (part of clinical work).
Local principal investigator in a global phase III
study of a GLP-1 agonist for children: LS (part
of clinical work). Lecturing fees from industry: KJ
(part of clinical work).
Funding information
YTL was supported by funding from the regional
agreement between StockholmCounty Council and
Karolinska Institutet, clinical research appoint-
ment. The funder had no role in preparation of the
manuscript.
Data availability statement
Data sharing is not applicable to this article as no
new data were created or analyzed in this study.
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