# 30 - 414 Evaluation and Management of Obesity

### 414 Evaluation and Management of Obesity

FATTY LIVER DISEASE  Obesity is strongly associated with the pres­
ence of ectopic fat in hepatocytes. In a subset of patients, this can 
progress to nonalcoholic steatohepatitis (NASH), which can progress 
to fibrosis, which is a precursor to cirrhosis (Chap. 354). The reported 
incidence of NASH-related cirrhosis and of hepatocellular carcinoma 
has increased markedly in step with the increase in the prevalence of 
obesity in adolescents and adults.
TYPE 2 DIABETES  The insulin resistance characteristic of the over­
nourished state strongly predisposes to the development of type 2 
diabetes in people who, largely for genetic reasons, are less able to 
maintain the high levels of insulin secretion over many decades. 
Impaired glucose tolerance and type 2 diabetes are among the most 
common complications of obesity (Chap. 415).
Endocrine Complications 
In females, the insulin resistance/
hyperinsulinemia frequently found in obesity strongly predisposes to 
the development of polycystic ovaries, characterized by irregular men­
struation, anovulatory infertility, and hirsutism due to hyperandrogen­
ism. In males, obesity is more often associated with a degree of central 
hypogonadism, where low circulating testosterone is associated with levels 
of luteinizing hormone and follicle-stimulating hormone that do not 
rise appropriately to compensate for the testosterone-deficient state.
Dermatologic Complications 
Obesity can result in problems 
with excessive skin folds that can cause discomfort through mechanical 
irritation and can also become infected with fungi. Insulin resistance/
hyperinsulinemia is associated with acanthosis nigricans, where areas 
such as axilla, groin, and the back of neck develop velvety hyperpig­
mentation. Hidradenitis suppurativa is a potentially disabling skin con­
dition strongly associated with obesity. It is characterized by recurrent 
boils often with chronically draining sinus tracts affecting skin areas 
containing apocrine sweat glands.
Cardiovascular Complications 
People with obesity, even if they 
do not have diabetes, have increased morbidity and mortality from 
atherothrombotic vascular disease, including coronary artery disease 
and stroke. The factors that result in this are complex and involve 
increased prevalence of hypertension, dyslipidemia, and insulin resis­
tance/hyperinsulinemia. The rare condition of thrombotic thrombo­
cytopenic purpura, which causes microvascular platelet thrombosis, 
thrombocytopenia, and hemolytic anemia due to the presence of 
abnormally large von Willebrand factor multimers, is strongly associ­
ated with obesity.
Independent of occlusive arterial disease, people with obesity are 
also at increased risk of heart failure, particularly characterized primar­
ily by diastolic dysfunction, and of atrial fibrillation, the most common 
arrhythmia.
Respiratory Complications 
Exertional dyspnea is common in 
obesity, contributed to by the increased work required to move a 
greater mass as well as impacts of pressure on the diaphragm and tho­
racic cage on chest wall compliance. Enlargement of soft tissue of the 
mouth and throat and adipose depots around the airways contribute 
to the high prevalence of sleep apnea, although other factors such as 
central nocturnal hypoventilation, also contribute in some people.
Gastrointestinal Disorders 
Reflux esophagitis is the most com­
mon gastrointestinal complication of obesity, particularly occurring 
in those with high intraabdominal pressure. Gallstones are also more 
common in people with obesity, bringing increased risks of biliary 
colic, cholecystitis, pancreatitis, and gallbladder cancer.
Rheumatologic Disorders 
Osteoarthritis of the knee and gout 
are the two most common rheumatologic conditions clearly associated 
with obesity. Interestingly, despite obesity being described as a proin­
flammatory state, there is no evidence for an increase in rheumatoid 
arthritis or the seronegative arthritides among people with obesity.
Cancers 
Obesity is a risk factor for a number of common cancers. 
Indeed, it has recently been calculated that, at least in some countries, 
obesity has overtaken smoking as the greatest risk factor for developing 

cancer. Recent research has found that as the BMI increases by 5 kg/m2, 
cancer mortality increases by 10%. The largest effects are on colorec­
tal, kidney, and pancreatic cancer, adenocarcinoma of the esophagus, 
and, in women, endometrial carcinoma. The recent rapid increase in 
the prevalence of esophageal adenocarcinoma is likely related to the 
marked recent increase in reflux esophagitis due to the raised intraab­
dominal pressure (with or without hiatus hernia) characteristic of 
central obesity.

Response to Infection 
The fact that obesity can influence the 
outcome of some infections has become very apparent with the 
COVID-19 pandemic. Obese patients have a substantially worse out­
come if infected by SARS-CoV-2 through mechanisms that are as yet 
unclear. Obese patients also appear to be more susceptible to bacterial 
wound infections and postoperative sepsis.
Evaluation and Management of Obesity 
CHAPTER 414
Disorders of the Central Nervous System 
There is increasing 
evidence that obesity is a risk factor for dementia in later life, although 
how that risk is mediated is not clear. Idiopathic intracranial hyperten­
sion is a rare disorder that is strongly associated with obesity.
■
■CONCLUSION
Obesity is a medical disorder that has been greatly increasing in preva­
lence due to environmental factors that are ubiquitous in developed 
and developing countries. However, it is important to bear in mind that 
it is a highly heterogeneous condition, which in some people is attrib­
utable entirely to genetic causes, and that underlying genetic variation 
strongly influences the risk of obesity in all people. It is a serious con­
dition leading to multiple adverse health outcomes and considerable 
human suffering. As our understanding of its pathogenesis increases, 
our duty to treat obese patients with understanding and compassion 
and to develop new and better options for its treatment and prevention 
is worthy of emphasis.
■
■FURTHER READING
Farooqi IS, O’Rahilly S: The genetics of obesity in humans, in Endo­
text. KR Feingold et al (eds). South Dartmouth, MA, 2000.
Friedman JM: Leptin and the endocrine control of energy balance. Nat 
Metab 1:754, 2019.
Hall KD et al: The energy balance model of obesity: Beyond calories 
in, calories out. Am J Clin Nutr 115:1243, 2022.
Heymsfield SB, Wadden TA: Mechanisms, pathophysiology, and 
management of obesity. N Engl J Med 376:1492, 2017. 
Leibel RL et al: Changes in energy expenditure resulting from altered 
body weight. N Engl J Med 332:621, 1995.
NCD Risk Factor Collaboration (NCD-RISC): Worldwide trends 
in body-mass index, underweight, overweight, and obesity from 1975 
to 2016: A pooled analysis of 2416 population-based measurement 
studies in 128·9 million children, adolescents, and adults. Lancet 
390:2627, 2017.
O’Rahilly S: Harveian Oration 2016: Some observations on the causes 
and consequences of obesity. Clin Med (Lond) 16:551, 2016.
Robert F. Kushner

Evaluation and 

Management of Obesity
More than 70% of U.S. adults are considered to be overweight or have 
obesity, and the prevalence of obesity is increasing rapidly in most of 
the industrialized world. Children and adolescents also are developing 
greater rates of obesity, indicating that the current trends will accelerate

over time. Obesity is associated with an increased risk of multiple 
health problems, including hypertension, type 2 diabetes, dyslipidemia, 
obstructive sleep apnea, metabolic dysfunction-associated steatotic 
liver disease, degenerative joint disease, and some malignancies. Thus, 
it is important for health care professionals to identify, evaluate, and 
treat patients for obesity and associated complications and comorbid 
conditions.

■
■EVALUATION
Health care professionals should screen all adult patients for obesity 
and offer intensive lifestyle counseling including behavioral interven­
tions to promote sustained weight loss. The four main steps in the 
evaluation of obesity, as described below, are (1) a focused obesityrelated history that includes lifestyle questions about diet, physical 
activity, sleep, and stress; (2) a physical examination to determine the 
degree and type of obesity; (3) assessment of complications and comor­
bid conditions; and (4) assessment of the patient’s readiness to engage 
in weight management.
PART 12
Endocrinology and Metabolism
The Obesity-Focused History 
The first step in taking an obe­
sity-focused history is to approach the topic in a sensitive manner. The 
reason for this concern is that the word obesity is a highly charged, 
emotive term. It has a significant pejorative meaning for many patients, 
leaving them feeling judged and blamed when labeled as such. This is 
not the case when patients are told that they have other chronic dis­
eases such as diabetes or hypertension. Patients prefer that clinicians 
use more neutral words or terms such as weight, excess weight, body 
mass index (BMI), or unhealthy weight, versus more perceived stigma­
tizing terms such as obesity, morbid obesity, or fatness.
Information from the history should address the following seven 
questions:
•	 What factors contribute to the patient’s weight gain and obesity?
•	 How is obesity affecting the patient’s health?
•	 What is the patient’s level of risk from obesity?
•	 What does the patient find difficult about managing weight?
•	 What are the patient’s goals and expectations?
•	 What is the patient’s motivation to begin a weight management 
program?
•	 What kind of help does the patient need?
Although the majority of cases of obesity are promoted by biopsy­
chosocial and behavioral factors that affect diet and physical activity 
patterns, the history may suggest secondary causes that merit further 
evaluation. Disorders to consider include polycystic ovarian syndrome, 
hypothyroidism, Cushing’s syndrome, and hypothalamic disease. Druginduced weight gain also should be considered. Common causes include 
medications for diabetes (insulin, sulfonylureas, thiazolidinediones), 
steroid hormones, antipsychotic agents (clozapine, olanzapine, risperi­
done), mood stabilizers (lithium), antidepressants (tricyclics, mono­
amine oxidase inhibitors, paroxetine, mirtazapine), and antiepileptic 
drugs (valproate, gabapentin, carbamazepine). Other medications, such 
as nonsteroidal anti-inflammatory drugs and calcium channel blockers, 
may cause peripheral edema but do not increase body fat.
The patient’s current diet and physical activity patterns may reveal 
factors that contribute to the development of obesity and may identify 
behaviors to target for treatment. Physical fitness and sedentary lifestyle, 
in particular, are important predictors of all-cause mortality rate inde­
pendent of BMI and body composition, which highlights the importance 
of taking a physical activity and exercise history during examination as 
well as emphasizing physical activity as a treatment approach.
Inquiring about sleep health that addresses regularity, duration, 
efficiency, and satisfaction is also important. Although the mechanisms 
are uncertain, sleep deprivation is associated with metabolic alterations 
in appetite regulation, sympathetic nervous system overactivity, insulin 
sensitivity, and changes in circadian rhythm. Stress may also contribute 
to obesity, in part due to activation of the adrenal cortical axis and 
elevated cortisol levels and its impact on emotional health and behav­
iors. This historic information is best obtained by the combination of a 
questionnaire and an interview.

TABLE 414-1  Classification of Weight Status and Disease Risk
BODY MASS 
INDEX (kg/m2)
OBESITY 
CLASS
DISEASE RISK
CLASSIFICATION
Underweight
<18.5
—
—
Healthy weight
18.5–24.9
—
—
Overweight
25.0–29.9
—
Increased
Obesity
30.0–34.9
I
High
Obesity
35.0–39.9
II
Very high
Extreme obesity
≥40
III
Extremely high
Source: Reproduced with permission from WHO Consultation on Obesity (1997): 
Geneva, Switzerland), World Health Organization; 1997.
BMI and Waist Circumference 
Three key anthropometric mea­
surements are important in evaluating the degree of obesity: weight, 
height, and waist circumference. The BMI, calculated as weight (kg)/
height (m)2 or as weight (lb)/height (in)2 × 703, is used to classify 
weight status and risk of disease (Table 414-1). BMI is correlated 
with body fat and is related to disease risk. Lower BMI thresholds for 
overweight and obesity have been proposed for the Asia-Pacific region 
since this population appears to be at risk for glucose and lipid abnor­
malities at lower body weights. The problem with BMI is that it only 
measures the size of an individual. It does not measure body composi­
tion, distribution of body fat, health, quality of life, or any individual 
characteristics. BMI has many limitations but is still useful for screen­
ing and as a population estimate of increased morbidity and mortality. 
Currently, direct measurement of excess body fat is not universally 
practical in the clinical setting.
Excess abdominal fat, assessed by measurement of waist circumfer­
ence or waist-to-hip ratio, is independently associated with a higher 
risk for metabolic syndrome, diabetes mellitus, and cardiovascular dis­
ease. Measurement of the waist circumference is a surrogate for visceral 
adipose tissue and should be performed in the horizontal plane above 
the iliac crest in individuals with a BMI ≤35 kg/m2 (Table 414-2).
Obesity-Associated Complications and Comorbid Conditions 

The evaluation of complications and comorbid conditions should 
be based on presentation of symptoms, risk factors, and index of 
suspicion. For all patients, a fasting lipid profile (total, low-density 
lipoprotein, and high-density lipoprotein cholesterol and triglyceride 
levels), chemistry panel, and glycated hemoglobin should be per­
formed, and blood pressure determined. Symptoms and diseases that 
are directly or indirectly related to obesity are listed in Table 414-3. 
TABLE 414-2  Ethnic-Specific Cutpoint Values for Waist Circumference
ETHNIC GROUP
WAIST CIRCUMFERENCE
Europeans
  Men
>94 cm (>37 in)
  Women
>80 cm (>31.5 in)
South Asians and Chinese
  Men
>90 cm (>35 in)
  Women
>80 cm (>31.5 in)
Japanese
  Men
>85 cm (>33.5 in)
  Women
>90 cm (>35 in)
Ethnic South and Central Americans
Use South Asian recommendations 
until more specific data are available.
Sub-Saharan Africans
Use European data until more specific 
data are available.
Eastern Mediterranean and Middle 
Eastern (Arab) populations
Use European data until more specific 
data are available.
Source: Reproduced with permission from KG Alberti, P Zimmet, J Shaw; IDF 
Epidemiology Task Force Consensus Group. The metabolic syndrome-a new 
worldwide definition. Lancet 366:1059, 2005.

TABLE 414-3  Obesity-Related Organ Systems Review
Cardiovascular
Respiratory
  Hypertension
  Dyspnea
  Congestive heart failure
  Obstructive sleep apnea
  Cor pulmonale
  Hypoventilation syndrome
  Varicose veins
  Pickwickian syndrome
  Pulmonary embolism
  Asthma
  Coronary artery disease
Gastrointestinal
Endocrine
  Gastroesophageal reflux disease
  Metabolic syndrome
  Nonalcoholic fatty liver disease
  Type 2 diabetes
  Cholelithiasis
  Dyslipidemia
  Hernias
  Polycystic ovarian syndrome
  Colon cancer
Musculoskeletal
Genitourinary
  Hyperuricemia and gout
  Urinary stress incontinence
  Immobility
  Obesity-related glomerulopathy
  Osteoarthritis (knees and hips)
  Hypogonadism (male)
  Low back pain
  Breast and uterine cancer
  Carpal tunnel syndrome
  Pregnancy complications
Psychological
Neurologic
  Depression/low self-esteem
  Stroke
  Body image disturbance
  Idiopathic intracranial hypertension
  Social stigmatization
  Meralgia paresthetica
Integument
  Dementia
  Striae distensae
  Stasis pigmentation of legs
  Lymphedema
  Cellulitis
  Intertrigo, carbuncles
  Acanthosis nigricans
  Acrochordons (skin tags)
  Hidradenitis suppurativa
Stage 0
No
complications
BMI ≥25
BMI ≥25
BMI ≥30
BMI 25–29.9
BMI
Secondary
Tertiary
Tertiary
Prevent complications
Treat complications
Treat complications
Treatment/
prevention
Lifestyle
Lifestyle
Lifestyle
Consider medication
Plus medication
consider surgery
Suggested
therapy
• Metabolically healthy
 obese
• No biomechanical
 complications
Examples
FIGURE 414-1  Staging the severity of obesity using the American Association of Clinical Endocrinology clinical practice guidelines. AHI, apnea-hypopnea index; BMI, 
body mass index; NASH, nonalcoholic steatohepatitis; OSA, obstructive sleep apnea; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index (a patientreported outcome measure for osteoarthritis registering pain, stiffness, and function). (Data from WT Garvey et al: American Association of Clinical Endocrinologists and 
American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract 22(Suppl 3):1, 2016.)

Although individuals vary, the number and severity of organ-specific 
complications and comorbid conditions usually rise with increasing 
levels of obesity.

Identifying the High-Risk Patient 
Efforts are under way to 
develop more practical and useful assessments to identify patients who 
are at high risk in addition to using BMI alone. Analogous to other 
staging systems commonly used for congestive heart failure or chronic 
kidney disease, the American Association of Clinical Endocrinology 
(AACE) and the American College of Endocrinology (ACE) guide­
lines advocate a simple and clinically useful obesity disease staging 
system that is based on ethnic-specific BMI cutoffs in conjunction 
with assessment for adiposity-related complications (Fig. 414-1). Stage 0 
is assigned to individuals who are overweight or have obesity by BMI 
classification but have no complications, whereas stages 1 and 2 are 
defined as individuals who are overweight or have obesity by BMI 
classification and have one or more mild-moderate complications 
(stage 1) or at least one severe complication (stage 2). A different func­
tional staging system for obesity, called the Edmonton Obesity Staging 
System (EOSS), classifies individuals with obesity into five graded 
categories (0–4), based on their morbidity and health-risk profile along 
three domains—medical, functional, and psychological. In this system, 
staging occurs independent of BMI.
Evaluation and Management of Obesity 
CHAPTER 414
Assessing the Patent’s Readiness to Change 
An attempt to 
initiate lifestyle changes when the patient is not ready usually leads 
to frustration and may hamper future weight-loss efforts. Assessment 
includes patient motivation and support, stressful life events, psychi­
atric status, time availability and constraints, and appropriateness of 
goals and expectations. Readiness can be viewed as the balance of two 
opposing forces: (1) motivation, or the patient’s desire to change; and 
(2) resistance, or the patient’s barriers to change.
A helpful method to begin a readiness assessment is to use the 
motivational interviewing technique of “anchoring” the patient’s 
interest and confidence to change on a numerical scale. With this 
technique, the patient is asked to rate—on a scale from 0 to 10, with 0 
being not so important (or confident) and 10 being very important (or 
confident)—their level of interest in and confidence about engaging in 
Stage 1
Stage 2
Mild-moderate
complications
Severe
complications
• Pre-hypertension
• Hepatic steatosis
• OSA with AHI 5–30
 and mild symptoms
• Osteoarthritis with
 WOMAC score 1–5
• Prediabetes
• Metabolic syndrome
• Type 2 diabetes
• NASH
• Hypertension
• OSA with symptoms or AHI >30
• Osteoarthritis with WOMAC score
 5–10 or knee replacement surgery

weight management at this time. This exercise helps establish readiness 
to change and also serves as a basis for further dialogue.

TREATMENT
Obesity
THE GOAL OF THERAPY
The primary goals of treatment are to improve obesity-related com­
plications and comorbid conditions and quality of life and reduce 
the risk of developing future obesity-related complications. Infor­
mation obtained from the history, physical examination, and diag­
nostic tests is used to determine risk and develop a treatment plan. 
The decision of how aggressively to treat the patient and which 
modalities to employ is determined by using shared decision-mak­
ing that includes the patient’s risk status, expectations and personal 
values, and available resources. Not all patients who are deemed 
to have obesity by BMI screening need to be treated, since BMI 
alone is an imperfect measurement of the disease of obesity. How­
ever, patients who present with obesity-related complications and 
comorbidities and who would benefit from weight-loss intervention 
should be managed proactively. Therapy for obesity always begins 
with lifestyle management and may include pharmacotherapy or 
bariatric surgery, depending on BMI risk category (Table 414-4). 
Setting an initial weight-loss goal of 8–10% over 6 months is a realistic 
and practical target.
PART 12
Endocrinology and Metabolism
LIFESTYLE MANAGEMENT
Obesity care involves attention to three essential elements of life­
style: dietary habits, physical activity, and behavior modification. 
Because obesity is fundamentally a disease of energy imbalance, all 
patients must learn how and when energy is consumed (diet), how 
and when energy is expended (physical activity), and how to incor­
porate this information into their daily lives (behavioral therapy). 
Lifestyle management has been shown to result in a modest (typically 
3–5 kg) weight loss when compared with no treatment or usual care.
Diet Therapy  The primary focus of diet therapy is to reduce 
overall calorie consumption. Guidelines from the American Heart 
Association/American College of Cardiology/The Obesity Society 
(AHA/ACC/TOS) recommend initiating treatment with a calorie 
deficit of 500–750 kcal/d compared with the patient’s habitual diet. 
Alternatively, a diet of 1200–1500 kcal/d for women and 1500–1800 
kcal/d for men (adjusted for the individual’s body weight) can 
be prescribed. This reduction is consistent with a goal of losing 
~1–2 lb/week. The calorie deficit can be instituted through dietary 
substitutions or alternatives. Examples include choosing smaller 
portion sizes, eating more fruits and vegetables, consuming more 
whole-grain cereals, selecting leaner cuts of meat and skimmed 
dairy products, reducing consumption of fried foods and other 
foods with added fats and oils, and drinking water instead of 
sugar-sweetened beverages. It is important that dietary counseling 
remains patient centered and that the selected goals are SMART 
(specific, measurable, agreed upon, realistic, timely).
The macronutrient composition of the diet will vary with the 
patient’s preference and medical condition. The 2020 U.S. Depart­
ment of Agriculture Dietary Guidelines for Americans (Chap. 343), 
which focus on health promotion and risk reduction, can be applied 
to treatment of patients who are overweight or have obesity. The 
TABLE 414-4  A Guide to Opting for Treatment for Obesity
TREATMENT
25–26.9
27–29.9
30–34.9
35–39.9
≥40
Diet, exercise, behavioral therapy
With comorbidities
With comorbidities
+
+
+
Pharmacotherapy
—
With comorbidities
+
+
+
Surgery
—
—
—
With comorbidities
+
Source: Reproduced from U.S. Department of Health and Human Services Public Health Service. National Institute of Health National Heart, Lung and Blood Institute. The 
Practical Guide Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NIH Publication Number 00-4084. October 2000.

recommendations include maintaining a diet rich in whole grains, 
fruits, vegetables, and dietary fiber; decreasing sodium intake to 
<2300 mg/d; consuming fat-free or low-fat dairy products; and 
keeping added sugars and saturated fat intake to <10% of daily calo­
ries. Application of these guidelines to specific calorie goals can be 
found on the website www.choosemyplate.gov. Since portion control 
is one of the most difficult strategies for patients to manage, the use 
of preprepared products such as meal replacements is a simple and 
convenient suggestion. Examples include frozen entrees, protein 
shakes, and bars. Use of meal replacements in the diet has been 
shown to result in a 7–8% weight loss.
Numerous randomized trials comparing diets of different mac­
ronutrient composition (e.g., low-carbohydrate, low-fat, Mediterra­
nean) have shown that weight loss depends primarily on reduction 
of total caloric intake and adherence to the prescribed diet, not the 
specific proportions of carbohydrate, fat, and protein in the diet. 
The macronutrient composition will ultimately be determined by 
the patient’s taste preferences, cooking style, and culture. However, 
the patient’s underlying medical problems are also important in 
guiding the recommended dietary composition. The dietary pre­
scription will vary according to the patient’s metabolic profile and 
risk factors. A consultation with a registered nutritionist for medical 
nutrition therapy is particularly useful in considering patient pref­
erence and treatment of comorbid diseases.
Another dietary approach to consider is based on the concept of 
energy density, which refers to the number of calories (i.e., amount 
of energy) a food contains per unit of weight. People tend to ingest 
a constant volume of food regardless of caloric or macronutrient 
content. Adding water or fiber to a food decreases its energy density 
by increasing weight without affecting caloric content. Examples of 
foods with low energy density include soups, fruits, vegetables, oat­
meal, and lean meats. Dry foods and high-fat foods such as pretzels, 
cheese, egg yolks, potato chips, and red meat have a high energy 
density. Diets containing low-energy-dense foods have been shown 
to control hunger and thus to result in decreased caloric intake and 
weight loss.
Occasionally, very-low-calorie diets (VLCDs) are prescribed as a 
form of aggressive dietary therapy. The primary purpose of a VLCD 
is to promote a rapid and significant (13- to 23-kg) short-term 
weight loss over a 3- to 6-month period. The proprietary formulas 
designed for this purpose typically supply ≤800 kcal, 50–80 g of pro­
tein, and 100% of the recommended daily intake for vitamins and 
minerals. Indications for initiating a VLCD include the involvement 
of well-motivated individuals who have moderate to severe obesity, 
have failed at more conservative approaches to weight loss, and 
have a medical condition that would be immediately improved with 
rapid weight loss. These conditions include poorly controlled type 2 
diabetes, hypertriglyceridemia, obstructive sleep apnea, and symp­
tomatic peripheral edema. In the DiRECT trial of patients with type 
2 diabetes and obesity, a low-energy formula diet (825–853 kcal/d) 
was administered for 3 months following by a structured monthly 
program. At 12 months, almost half of the participants achieved 
remission to a nondiabetic state off of all antidiabetic drugs. Use 
of formula diets should be prescribed by trained practitioners in a 
medical care setting where medical monitoring and high-intensity 
lifestyle intervention can be provided.
Physical Activity Therapy  Although exercise alone is only 
moderately effective for weight loss, the combination of dietary 
BMI CATEGORY (kg/m2)

modification and exercise is the most effective behavioral approach 
for the treatment of obesity. The most important role of exercise 
appears to be in the maintenance of weight loss. The 2018 Physical 
Activity Guidelines for Americans (www.health.gov/paguidelines) 
recommend that adults should engage in 150 min of moderateintensity or 75 min a week of vigorous-intensity aerobic physical 
activity per week, preferably spread throughout the week. Focusing 
on simple ways to add physical activity into the normal daily rou­
tine through leisure activities, travel, and domestic work should be 
suggested. Examples include brisk walking, using the stairs, doing 
housework and yard work, and engaging in sports. Additionally, it 
is important to reduce sedentary behavior, which is associated with 
all-cause and cardiovascular disease mortality in adults. Asking the 
patient to use a wearable activity tracker to monitor total accumula­
tion of steps or kcal expended as part of the activities of daily living 
is a useful strategy. Step counts are highly correlated with activity 
level. Studies have demonstrated that lifestyle activities are as effec­
tive as structured exercise programs for improving cardiorespira­
tory fitness and weight loss. A high level of physical activity (>300 
min of moderate-intensity activity per week) is often needed to lose 
weight and sustain weight loss. These exercise recommendations 
are daunting to most patients and need to be implemented gradu­
ally. Consultation with an exercise physiologist or personal trainer 
may be helpful.
Behavioral Therapy  Cognitive behavioral therapy is used to help 
change and reinforce new dietary and physical activity behaviors. 
Strategies include self-monitoring techniques (e.g., journaling, 
weighing, and measuring food and activity); stress management; 
stimulus control (e.g., using smaller plates, not eating in front of 
the television or in the car); social support; problem solving; and 
cognitive restructuring to help patients develop more positive and 
realistic thoughts about themselves. When recommending any 
behavioral lifestyle change, the patient should be asked to identify 
what, when, where, and how the behavioral change will be per­
formed. The patient should keep a record of the anticipated behav­
ioral change so that progress can be reviewed at the next office visit. 
Because these techniques are time consuming to implement, their 
supervision is often undertaken by ancillary office staff, such as an 
advanced practice provider or registered nutritionist.
PHARMACOTHERAPY
Adjuvant pharmacologic treatments should be considered for 
patients with a BMI ≥30 kg/m2 or a BMI ≥27 kg/m2 who have con­
comitant obesity-related diseases and for whom dietary and physi­
cal activity therapy has not been successful. When an antiobesity 
medication is prescribed, patients should be actively engaged in a 
lifestyle program that provides the strategies and skills needed to use 
the drug effectively since such support increases total weight loss.
Medications for obesity have traditionally fallen into two major 
categories: those that affect appetite and those that inhibit gastro­
intestinal fat absorption. However, since the introduction of more 
effective nutrient-stimulated hormone-based therapeutics in 2021, 
an additional designation of first- and second-generation medica­
tions has been adopted. Antiobesity medications are approved by 
the U.S. Food and Drug Administration (FDA) with an indication 
for chronic weight management, with the exception of phentermine 
and other sympathomimetics, which are only approved for shortterm use. The centrally active medications work biologically to 
suppress appetite, affecting hunger, satiety, and response to highly 
rewarding foods, and thus making it easier for patients to follow 
their dietary intentions to reduce caloric intake. In addition, one 
capsule that is considered a medical device was marketed in 2020. 
Characteristics of the currently approved antiobesity medications 
are shown in Table 414-5.
First-Generation Centrally Acting Medications  This class of 
medications directly targets neurotransmitters in the hypothalamus 
and reward centers in the central nervous system (Chap. 413) to 
affect satiety (feeling of fullness after a meal), hunger (the biologic 

sensation that prompts eating), and craving (intense desire for a 
specific food). By controlling appetite, these agents help patients 
reduce caloric intake without a sense of deprivation. The classic 
sympathomimetic adrenergic agents (benzphetamine, phendimet­
razine, diethylpropion, and phentermine) function by stimulating 
norepinephrine release or by blocking its reuptake. Among these 
agents, phentermine is the most commonly prescribed; however, 
there is limited long-term data on its effectiveness. A 2002 review of 
six randomized, placebo-controlled trials of phentermine for weight 
control found that patients lost 0.6–6.0 additional kg of weight over 
2–24 weeks of treatment. The most common side effects of the 
amphetamine-derived agents are restlessness, insomnia, dry mouth, 
constipation, and increased blood pressure and heart rate.

Evaluation and Management of Obesity 
CHAPTER 414
Phentermine/topiramate (PHEN/TPM) is a combination drug 
that contains a catecholamine releaser (phentermine) and an anti­
convulsant (topiramate). Topiramate is approved by the FDA as an 
anticonvulsant for the treatment of epilepsy and for the prophylaxis 
of migraine headaches. Weight loss was identified as an unintended 
side effect of topiramate during clinical trials for epilepsy. The 
mechanism responsible for weight loss is uncertain but is thought 
to be mediated through the drug’s modulation of γ-aminobutyric 
acid receptors, inhibition of carbonic anhydrase, and antagonism 
of glutamate. PHEN/TPM has undergone two 1-year pivotal ran­
domized, placebo-controlled, double-blind trials of efficacy and 
safety: EQUIP and CONQUER. In a third study, SEQUEL, 78% 
of CONQUER participants continued to receive their blinded 
treatment for an additional year. All participants received diet 
and exercise counseling. Mean percent weight loss for participants 
randomized to medication and placebo are displayed in Fig. 414-2. 
Intention-to-treat 1-year placebo-subtracted weight loss for PHEN/
TPM was 9.3% (15-mg/92-mg dose) and 6.6% (7.5-mg/46-mg 
dose), respectively, in the EQUIP and CONQUER trials. Clinical 
and statistical dose-dependent improvements were seen in selected 
cardiovascular and metabolic outcome measurements that were 
related to the weight loss. The most common adverse events experi­
enced by the drug-randomized group were paresthesias, dry mouth, 
constipation, dysgeusia, and insomnia. Because of an increased risk 
of congenital fetal oral-cleft formation from topiramate, women 
of childbearing age should have a negative pregnancy test before 
treatment and monthly thereafter and use effective contraception 
consistently during medication therapy.
Naltrexone SR/bupropion SR (NB) is a combination of an opioid 
antagonist and a dopamine and norepinephrine reuptake inhibitor, 
respectively. Individually, naltrexone is approved by the FDA for 
the treatment of alcohol dependence and for the blockade of the 
effects of exogenously administered opioids, whereas bupropion 
is approved as an antidepressant and smoking cessation aid. As a 
combination drug, each component works in consort: bupropion 
stimulates secretion of α-melanocyte-stimulating hormone (MSH) 
from proopiomelanocortin (POMC), whereas naltrexone blocks 
the feedback inhibitory effects of opioid receptors activated by 
the β-endorphin released in the hypothalamus, thus allowing the 
inhibitory effects of MSH to reduce food intake.
The medication has undergone three randomized, placebocontrolled, double-blind trials for efficacy and safety. Participants 
were randomized to receive NB (8 mg/90 mg two tablets bid) or 
placebo in the three COR studies. Whereas participants received 
standardized nutritional and exercise counseling in COR-I and 
COR-II, a more intensive behavior modification program was 
provided in COR-BMOD (Table 414-5). Intention-to-treat 1-year 
placebo-subtracted weight loss was 4.8%, 5.1%, and 4.2%, respec­
tively, in the COR-I, COR-II, and COR-BMOD trials. Clinical and 
statistical dose-dependent improvements were seen in selected car­
diovascular and metabolic outcome measurements that were related 
to the weight loss. However, the medication led to slight increases 
or smaller decreases in blood pressure and pulse than placebo. The 
most common adverse events experienced by the drug-randomized 
groups were nausea, constipation, headache, vomiting, dizziness, 
diarrhea, insomnia, and dry mouth.

TABLE 414-5  Antiobesity Medications
DRUG 
CHARACTERISTIC
PHENTERMINE
ORLISTAT
PHEN/TPM
NAL/BUP
LIRAGLUTIDE
SEMAGLUTIDE
TIRZEPATIDE
Mechanism of 
action
Sympathomimetic, 
increases 
norepinephrine 
release in CNS
Gastrointestinal 
lipase enzyme 
inhibitor
Phen: 
sympathomimetic 
in CNS;
TPM: modulates 
GABA receptors in 
the CNS
Route of 
administration, 
frequency, and 
dose
Oral, once to 3 
times daily, doses 
of 8, 15, 30, and 
37.5 mg
Oral, 3 times daily, 
within 1 h of fatcontaining meals
Oral, once daily. 
Start 3.75/23 mg/d 
× 2 weeks, then 
6.5/46 mg/d; can 
escalate to max 
dose of 15/2 mg/d
PART 12
Endocrinology and Metabolism
Percent weight 
loss (placebo 
subtracted)a
4.4%
4.1%
8.0%
5.1%
5.4%
12.5%
17.8%
Most common 
adverse effects
Dry mouth
Insomnia
Constipation
Headache
Dizziness
Steatorrhea
Increased 
defecation
Oily spotting
Liquid stool
Fecal urgency
Paresthesia
Dry mouth
Constipation
Headache
Insomnia
Dizziness
Contraindications
Uncontrolled 
hypertension, 
untreated 
hyperthyroidism, 
within 14 d of 
MAOI use
Chronic 
malabsorption
Uncontrolled 
hypertension, 
untreated 
hyperthyroidism, 
history of 
glaucoma, 
calcium oxalate 
nephrolithiasis, 
within 14 d of 
MAOI use
aBased on maximal dose.
Abbreviations: CNS, central nervous system; GABA, γ-aminobutyric acid; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide 1; MAOI, monoamine oxidase 
inhibitor; MEN, multiple endocrine neoplasia; Nal/Bup, naltrexone/bupropion; Phen/TPM, phentermine/topiramate; POMC, proopiomelanocortin; qW, every week.
Liraglutide was the first glucagon-like peptide 1 receptor agonist 
(GLP-1 RA) with 97% homology to human GLP-1 that introduces 
nutrient-stimulated, hormone-based therapy for the treatment of 
obesity. In addition to its effect as an incretin hormone (glucoseinduced insulin secretion), liraglutide inhibits both gastric empty­
ing and glucagon secretion and stimulates GLP-1 receptors in the 
arcuate nucleus of the hypothalamus, the nucleus tractus solitarius 
of the brainstem, and projections to other appetite-modulating relay 
nuclei to reduce appetite. As a result of molecular modifications of 
the structure, liraglutide has reduced susceptibility to DPP-4 and 
can be dosed once daily by subcutaneous (SC) administration with 
a half-life of ~11–15 h. Liraglutide was initially approved for the 
treatment of type 2 diabetes in the United States in 2010 at doses 
up to 1.8 mg once daily. It was subsequently approved for obesity 
treatment at doses up to 3.0 mg once daily in 2014 for adults and, in 
2020, for adolescents (aged ≥12 years).
Specifically targeting obesity, liraglutide has undergone five ran­
domized, double-blind, placebo-controlled trials in adults called 
SCALE (Satiety and Clinical Adiposity–Liraglutide Evidence) 
involving >5000 adult participants to evaluate its efficacy and safety 
for weight management. All participants received diet and physi­
cal activity counseling and were randomized to receive liraglutide 
(3.0 mg SC daily) or placebo with the primary outcome of change 
in body weight. Intention-to-treat 1-year placebo-subtracted weight 
loss for these trials ranged from 3.4 to 6.1%. Clinical and statistical 
dose-dependent improvements were seen in selected cardiovascular 

Nal: blocks opioidmediated POMC 
autoinhibition; bup: 
activates POMC in 
the hypothalamus
GLP-1 receptor 
agonist
GLP-1 receptor 
agonist
GLP-1/GIP dual 
receptor agonist
Oral, 1 tablet 
(8 mg/90 mg) 
qAM × 1 week; 1 
tablet in morning 
and evening × 1 
week; 2 tablets 
in morning and 1 
tablet in evening 
× 1 week; then 2 
tablets in morning 
and 2 tablets in 
evening
Subcutaneous, 
once daily; initiate 
at 0.6 mg/d × 1 
week; increase by 
0.6 mg weekly to 
3 mg/d
Subcutaneous, 
once weekly; 0.25 
mg qW × 4 weeks, 
then 0.5 mg qW 
× 4 weeks, then 1 
mg qW × 4 weeks, 
then 1.7 mg qW × 
4 weeks, then 2.4 
mg qW
Subcutaneous, 
once weekly; 2.5 
mg qW × 4 weeks, 
then 5 mg qW × 
4 weeks, then 7.5 
mg qW × 4 weeks, 
then 10 mg qW × 
4 weeks, then 12.5 
mg qW, then 15 
mg qW
Nausea
Constipation
Headache
Vomiting
Dizziness
Insomnia
Nausea
Diarrhea
Constipation
Dyspepsia
Vomiting
Nausea
Diarrhea
Constipation
Dyspepsia
Vomiting
Nausea
Diarrhea
Constipation
Abdominal pain
Uncontrolled 
hypertension, 
history of seizures, 
bulimia or anorexia 
nervosa, within 
14 d of MAOI use, 
long-term opioid 
use
Personal or 
family history of 
medullary thyroid 
cancer,
MEN type 2; 
pancreatitis is a 
caution
Personal or 
family history of 
medullary thyroid 
cancer; MEN type 
2; pancreatitis is a 
caution
Personal or 
family history of 
medullary thyroid 
cancer,
MEN type 2;
pancreatitis is a 
caution
and metabolic outcome measurements. In SCALE TEENS, which 
involved adolescents with obesity (average age 14.6 years), the 
liraglutide-treated group demonstrated a placebo-subtracted weight 
loss of 5%. The most common adverse events from the SCALE tri­
als were nausea, diarrhea, constipation, and vomiting, which were 
reported as mild and transient. GLP-1 agonists should not be pre­
scribed in patients with a family or personal history of medullary 
thyroid cancer or multiple endocrine neoplasia.
Setmelanotide is a melancortin-4 (MC4) receptor agonist that 
was FDA approved in 2020 for daily SC administration for chronic 
weight management in adults and pediatric patients 6 years of age 
and older with monogenic or syndromic obesity due to BardetBiedl syndrome (BBS) or POMC, proprotein convertase subtilisin/
kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. The 
medication addresses the underlying hyperphagia and specific 
molecular mechanism of these rare genetic diseases. The most 
common side effects include injection site reactions, skin hyperpig­
mentation, nausea, and spontaneous penile erections.
First-Generation Peripherally Acting Medication  Orlistat is cur­
rently the only medication in this class. It is a synthetic hydroge­
nated derivative of a naturally occurring lipase inhibitor, lipostatin, 
that is produced by the mold Streptomyces toxytricini. This drug 
is a potent, slowly reversible inhibitor of pancreatic, gastric, and 
carboxylester lipases and phospholipase A2, which are required for 
the hydrolysis of dietary fat into fatty acids and monoacylglycerols.

Orlistat
Phen/TPM
NB
Lira
Sema
TZP
24.3

Percent weight loss

10.4
10.9
10.2

8.8
6.1
5.8
6.5
6.1

1.9
1.3
1.2
1.6

Davidson
CONQUER
COR-I
COR-II
COR-BMOD
Sjostrom
EQUIP
FIGURE 414-2  One-year mean weight loss for antiobesity medications compared to placebo. Lira, liraglutide; NB, naltrexone/bupropion; Phen/TPM, phentermine/
topiramate; Sema, semaglutide; TZP, tirzepatide.
Orlistat acts in the lumen of the stomach and small intestine by 
forming a covalent bond with the active site of these lipases. Taken 
at a therapeutic dose of 120 mg tid, orlistat blocks the digestion and 
absorption of ~30% of dietary fat. After discontinuation of the drug, 
fecal fat content usually returns to normal within 48–72 h.
Multiple randomized, double-blind, placebo-controlled studies 
have shown an intention-to-treat 1-year placebo-subtracted weight 
loss of 2.7–4.1%. Because orlistat is minimally (<1%) absorbed from 
the gastrointestinal tract, it has no systemic side effects. Tolerability 
is related to the malabsorption of dietary fat, and this is generally 
diminished as patients control their dietary fat intake. Because 
serum concentrations of the fat-soluble vitamins D and E and 
β-carotene may be reduced by orlistat treatment, vitamin supple­
ments are recommended to prevent potential deficiencies. Orlistat 
was approved for over-the-counter use in 2007.
Second-Generation Medications  Semaglutide is generally recog­
nized as the first drug in this category based on its greater weight 
loss efficacy and further chemical modification that allows for 
once-weekly SC administration with a longer half-life. Semaglutide 
was initially approved for the treatment of type 2 diabetes in the 
United States at doses up to 1.0 mg once weekly in 2017 and at 
2.0 mg once weekly in 2022. It was subsequently approved at doses 
up to 2.4 mg once weekly for chronic weight management for adults 
in 2021 and for adolescents in 2022.
Semaglutide has undergone multiple prospective, randomized, 
placebo-controlled trials in the STEP (Semaglutide Treatment 
Effect in People with Obesity) program that was designed to inves­
tigate the effect of semaglutide 2.4 mg SC weekly versus placebo on 
weight loss, safety, and tolerability in adults with obesity or over­
weight. Intention-to-treat placebo-subtracted weight loss for the 
STEP 1 to 4 trials ranged from 6.2 to 14.8% at 68 weeks depending 
on the population and study design, and loss of 12.6% occurred 
after 104 weeks for STEP 5. Clinical and statistical dose-dependent 
improvements were seen in selected cardiovascular and metabolic 
outcome measurements. The most common adverse effects include 
nausea, diarrhea, constipation, and vomiting. GLP-1 RAs should 

Drug
Placebo
20.9
17.4
Evaluation and Management of Obesity 
CHAPTER 414

11.3
9.3

5.7
5.1
4.5
3.1
2.6
2.4
SCALE MAIN
SCALE
STEP 1
STEP 3
STEP 4
SURMOUNT-1
SURMOUNT-3
not be prescribed in patients with a family or personal history of 
medullary thyroid cancer or multiple endocrine neoplasia.
In the STEP TEENS trial, adolescents with overweight or obesity 
randomized to semaglutide 2.4 mg achieved a 16.1% reduction 
in BMI versus a 0.6% increase for placebo. The recent SELECT 
(Semaglutide Effects on Cardiovascular Outcomes in People with 
Overweight or Obesity) trial demonstrated a 20% reduction in 
major adverse cardiovascular events in patients with preexisting 
cardiovascular disease and overweight or obesity but without dia­
betes who were randomized to semaglutide 2.4 mg versus placebo, 
and the STEP-HFpEF trial observed improved heart failure–related 
symptoms, physical limitations, and exercise function and reduced 
body weight and inflammation in patients randomized to semaglu­
tide versus placebo.
Tirzepatide is the first long-acting, weekly, injectable, dual GLP-1/
gastric inhibitory polypeptide (GIP) peptide analogue, engineered 
from the native GIP sequence with agonist activity at both the 
GLP-1 and GIP receptors with a half-life of ~117 h. Whereas GIP 
receptor agonism is equal to native GIP, the molecule’s GLP-1 recep­
tor affinity is approximately five times weaker than native GLP-1. 
GIP in the brain appears to act synergistically with GLP-1 recep­
tor activation to allow greater weight loss. Tirzepatide was FDA 
approved for type 2 diabetes in 2022 and subsequently approved 
for chronic weight management in adults in 2023, at 5-, 10-, and 
15-mg doses.
Tirzepatide has undergone multiple prospective, randomized, 
placebo-controlled trials in the SURMOUNT clinical development 
program that was designed to investigate the effect of tirzepatide 
5-, 10-, and 15-mg SC weekly doses versus placebo on weight 
loss, safety, and tolerability in adults with obesity or overweight. 
Intention-to-treat placebo-subtracted weight loss for SURMOUNT 
1 to 4 trials at the 15-mg dose ranged from 11.6 to 21.4% depend­
ing on the study population and design. Clinical and statistical 
dose-dependent improvements were seen in selected cardiovascular 
and metabolic outcome measurements. Similar to GLP-1 RAs, the 
most common adverse events are gastrointestinal (nausea, diarrhea,

constipation, and vomiting) and reported as mild and transient; 
tirzepatide should not be prescribed in patients with a family or 
personal history of medullary thyroid cancer or multiple endocrine 
neoplasia.

Oral Device  Gelesis100 is a nonsystemic, water-soluble gel that 
was approved by the FDA in 2019. In the stomach, the capsule 
releases the cellulose microgel, which absorbs water and forms 
a matrix with the consistency of food, occupying ~25% of the 
stomach. In the large intestine, it is broken down by enzymes and 
the cellulose is excreted. Gelesis100 and placebo were evaluated 
over 24 weeks in patients with BMI of 27 to ≤40 kg/m2 and fast­
ing plasma glucose of 90–145 mg/dL. Intention-to-treat, 24-week, 
placebo-subtracted weight loss was 2.1% (6.4 vs 4.4%). Gelesis100 
treatment had no apparent increased safety risks. The capsules are 
approved for patients with a BMI of ≥25 kg/m2, with or without 
comorbidities.
SURGERY
Bariatric surgery (Fig. 414-3) can be considered for patients with 
severe obesity (BMI ≥40 kg/m2) or for those with moderate obesity 
(BMI ≥35 kg/m2) associated with a number of comorbid conditions. 
The clinical benefits of bariatric surgery in achieving weight loss 
and alleviating metabolic complications and comorbidities have 
been attributed largely to changes in the physiologic responses of gut 
hormones, bile acid metabolism, the microbiota, and adipose tissue 
metabolism. Metabolic effects resulting from bypassing the foregut 
include altered responses of ghrelin, GLP-1, peptide YY3-36, and 
oxyntomodulin. Additional effects on food intake and body weight 
control may be attributed to changes in vagal signaling. The loss of 
fat mass, particularly visceral fat, is associated with multiple meta­
bolic, adipokine, and inflammatory changes that include improved 
insulin sensitivity and glucose disposal; reduced free fatty acid flux; 
increased adiponectin levels; and decreased interleukin 6, tumor 
necrosis factor α, and high-sensitivity C-reactive protein levels.
PART 12
Endocrinology and Metabolism
A
B
x
x
D
E
C
FIGURE 414-3  Bariatric surgical procedures. Examples of operative interventions used for surgical manipulation of the gastrointestinal tract. A. Laparoscopic adjustable 
gastric banding. B. Laparoscopic sleeve gastrectomy. C. The Roux-en-Y gastric bypass. D. Biliopancreatic diversion with duodenal switch. E. Biliopancreatic diversion.

Restrictive surgeries limit the amount of food the stomach can 
hold and slow the rate of gastric emptying. Laparoscopic adjustable 
gastric banding is the prototype of this category. The first banding 
device was approved for use in the United States in 2001. In con­
trast to previous devices, this band has a diameter that is adjustable 
by way of its connection to a reservoir that is implanted under the 
skin. Injection of saline into the reservoir and removal of saline 
from the reservoir tighten and loosen the band’s internal diameter, 
respectively, thus changing the size of the gastric opening. Although 
the mean percentage of total body weight lost at 5 years is estimated 
at 20–25%, longer-term follow-up has been more disappointing, 
leading to near abandonment of the procedure. In the laparoscopic 
sleeve gastrectomy, the stomach is restricted by stapling and dividing 
it vertically, removing ~80% of the greater curvature and leaving a 
slim banana-shaped remnant stomach along the lesser curvature. 
Weight loss after this procedure is superior to that after laparo­
scopic adjustable gastric banding.
The three restrictive-malabsorptive bypass procedures combine 
the elements of gastric restriction and selective malabsorption: 
Roux-en-Y gastric bypass, biliopancreatic diversion, and biliopan­
creatic diversion with duodenal switch (Fig. 414-3). These proce­
dures are routinely performed by laparoscopy.
These procedures generally produce a 28–33% average total 
body weight loss at 12–18 months followed by variable weight 
recurrence. Significant improvement in multiple obesity-related 
comorbid conditions, including type 2 diabetes, hypertension, dys­
lipidemia, obstructive sleep apnea, quality of life, and long-term 
cardiovascular events, has been reported. A meta-analysis of con­
trolled clinical trials comparing bariatric surgery versus no surgery 
showed that surgery was associated with a reduced odds ratio (OR) 
risk of global mortality (OR = 0.55), cardiovascular death (OR = 
0.58), and all-cause mortality (OR = 0.70).
Among the observed improvements in comorbidities, the pre­
vention and treatment of type 2 diabetes resulting from bariatric 
z
y
z
150 cm
y
100 cm