Annals of Internal Medicine䊛

In the Clinic®

Obesity Obesity-Related Health Problems

Screening and Prevention

Diagnosis

T
he role of internists in evaluating obesity is
to assess the burden of weight-related dis-
ease, mitigate secondary causes of weight Treatment
gain (medications, sleep deprivation), and so-
licit patient motivation for weight loss. Internists
should assess these factors and emphasize the Practice Improvement
importance of weight loss for the individual pa-
tient. All patients wishing to lose weight should
be encouraged to monitor their diet and physi-
cal activity and should be referred to high-
intensity behavioral programs. Some patients
with obesity may also benefit from pharmaco-
therapy or bariatric surgery.

CME/MOC activity available at Annals.org.

Physician Writers doi:10.7326/AITC201903050

Adam Gilden Tsai, MD,
MSCE CME Objective: To review current evidence for screening, prevention, diagnosis, treatment,
Daniel H. Bessesen, MD and practice improvement of obesity.
From Kaiser Permanente, Funding Source: American College of Physicians.
Metabolic-Surgical Weight
Management, Denver, Disclosures: Dr. Tsai, ACP Contributing Author, has nothing to disclose. Dr. Bessesen, ACP
Colorado (A.G.T.); and Contributing Author, reports other support from EnteroMedics/ReShape Lifesciences outside
University of Colorado School the submitted work. Disclosures can also be viewed at www.acponline.org/authors/icmje
of Medicine, Aurora, Colorado /ConflictOfInterestForms.do?msNum=M18-2783.
(D.H.B.).
With the assistance of additional physician writers, the editors of Annals of Internal Medicine
develop In the Clinic using MKSAP and other resources of the American College of
Physicians.
In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical
guidelines, please go to https://www.acponline.org/clinical_information/guidelines/.
© 2019 American College of Physicians

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 An estimated 39.6% of adults system. Most complications are
and 18.5% of children and ado- caused by the metabolic effects
1. Hales CM, Carroll MD,
lescents in the United States have of adipose tissue, but some are
Fryar CD, Ogden CL. Prev- obesity (1). Obesity is a serious caused by the mechanical effects
alence of obesity among
adults and youth: United health problem that has physical of increased body mass (see the
States, 2015–2016. NCHS and psychosocial consequences. Box: Obesity-Related Health
Data Brief. 2017:1-8.
[PMID: 29155689] It increases health care costs to Problems). Obesity is associated
2. Flegal KM, Kit BK, Orpana
H, Graubard BI. Associa-
patients and employers and re- with an overall increase in mortal-
tion of all-cause mortality duces productivity. Rates of obe- ity. The relationship between
with overweight and obe-
sity using standard body sity have increased dramatically weight and mortality follows a
mass index categories: a in the United States and other J-shaped curve, with increased
systematic review and
meta-analysis. JAMA. wealthy nations since 1970 and mortality at a body mass index
2013;309:71-82. [PMID:
23280227]
are now increasing rapidly in de- (BMI) less than 18.5 kg/m2 and a
3. Yu E, Ley SH, Manson JE, veloping countries.
Willett W, Satija A, Hu FB, BMI of 30 kg/m2 or greater. Mor-
et al. Weight history and
all-cause and cause- Access to treatment for obesity has tality is believed to be lowest at a
specific mortality in three improved. High-intensity behav- BMI of approximately 25 kg/m2.
prospective cohort studies.
Ann Intern Med. 2017; ioral treatment has increasingly A BMI in the overweight range in-
166:613-20. [PMID:
28384755]
become a standard of care. Five creases risk for several important
4. Arterburn DE, Olsen MK, medications are approved by the weight-related conditions, includ-
Smith VA, Livingston EH,
Van Scoyoc L, Yancy WS Jr, U.S. Food and Drug Administra- ing diabetes and hypertension.
et al. Association between tion (FDA) for treatment of obesity, Several studies have reported on
bariatric surgery and long-
term survival. JAMA. 4 of which have been approved patients with “metabolically
2015;313:62-70. [PMID: since 2012. Most patients have
25562267] healthy obesity” (those with obe-
5. Gregg EW, Jakicic JM, insurance coverage for bariatric sity and normal blood glucose lev-
Blackburn G, Bloomquist
P, Bray GA, Clark JM, et al;
surgery. However, treatment of els, blood pressure, and lipid
Look AHEAD Research obesity still faces many challenges.
Group. Association of the levels); subsequent research has
magnitude of weight loss Many clinicians and health system
shown that a high percentage of
and changes in physical leaders continue to view obesity as
fitness with long-term
a lifestyle choice rather than a such patients develop metabolic
cardiovascular disease
outcomes in overweight or chronic progressive metabolic dis- complications of excess adipose
obese people with type 2
diabetes: a post-hoc analy- ease, medications to treat obesity tissue over time. These patients
sis of the Look AHEAD
are excluded from most insurance may still be healthier than persons
randomised clinical trial.
Lancet Diabetes Endocri- formularies, and weight bias re- with normal weight but an adverse
nol. 2016;4:913-21. metabolic profile.
[PMID: 27595918] mains prevalent in health care and
6. Curry SJ, Krist AH, Owens society.
DK, Barry MJ, Caughey A highly publicized meta-analysis reported
AB, Davidson KW, et al;
US Preventive Services Internal medicine physicians play that a BMI in the overweight range (25.0 –29.9
Task Force. Behavioral an important role in helping their kg/m2) was associated with slightly lower mor-
weight loss interventions
to prevent obesity-related patients lose weight. Internists can tality than a normal BMI (18.5–24.9 kg/m2)
morbidity and mortality in
assist by highlighting the health and that class 1 obesity (BMI of 30 –34.9 kg/
adults: US Preventive
Services Task Force recom- benefits of a 5%- to 10%-reduction m2) was associated with mortality similar to
mendation statement.
in weight, helping patients set that for a normal BMI (2). Since publication of
JAMA. 2018;320:1163-
71. [PMID: 30326502] appropriate goals, providing in- the meta-analysis, several articles have pro-
7. Apovian CM, Aronne LJ, vided explanations for the “obesity paradox.”
Bessesen DH, McDonnell tensive behavioral interventions
ME, Murad MH, Pagotto themselves or referring patients, For example, a study that combined data from
U, et al; Endocrine Society. 3 large cohort studies (total n = 225 072) re-
Pharmacological manage- and prescribing weight loss medi-
ment of obesity: an Endo-
cation or referring for bariatric sur- ported that a maximum BMI greater than 25
crine Society clinical prac-
kg/m2 over a 16-year period was associated
tice guideline. J Clin gery in selected patients. Internists
Endocrinol Metab. 2015; with increased mortality (3).
100:342-62. [PMID: also play a critical role in monitor-
25590212] ing and managing obesity-related What is the evidence that
8. Domecq JP, Prutsky G,
Leppin A, Sonbol MB, comorbid conditions. intentional weight loss
Altayar O, Undavalli C,
et al. Clinical review: What are the health improves health outcomes?
drugs commonly associ-
ated with weight change: consequences of overweight There is strong evidence that in-
a systematic review and
meta-analysis. J Clin Endo- and obesity? tentional weight loss reduces the
crinol Metab. 2015;100:
363-70. [PMID:
Obesity, particularly severe obe- burden of obesity-related comor-
25590213] sity, affects nearly every organ bidities and improves overall

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 Obesity-Related Health Problems
Metabolic effects
Endocrine: Prediabetes and type 2 diabetes, dyslipidemia (low high-density
lipoprotein and high triglyceride levels)
Cardiovascular: Hypertension, coronary artery disease, stroke, congestive heart
failure, atrial fibrillation, venous stasis, venous thromboembolic disease (deep
venous thrombosis, pulmonary embolism)
Cancer: Multiple types, most commonly colorectal, postmenopausal breast, and
endometrial
Gastrointestinal: Gastroesophageal reflux disease, cholelithiasis, nonalcoholic fatty
liver disease, nonalcoholic steatohepatitis
Renal: Nephrolithiasis, proteinuria, chronic kidney disease
Genitourinary: In women, urinary stress incontinence, polycystic ovarian syndrome, 9. Hutfless S, Gudzune KA,
infertility, pregnancy complications; in men, benign prostatic hypertrophy, Maruthur N, Wilson RF,
erectile dysfunction Bleich SN, Lau BD, et al.
Strategies to prevent
Neurologic: Migraine, pseudotumor cerebri weight gain in adults: a
systematic review. Am J
Infections: Greater severity of influenza with severe obesity, skin and soft tissue Prev Med. 2013;45:e41-
infections 51. [PMID: 24237928]
Mechanical effects 10. Mozaffarian D, Hao T,
Rimm EB, Willett WC, Hu
Pulmonary: Obstructive sleep apnea, pulmonary hypertension, restrictive lung FB. Changes in diet and
disease, chronic hypoxemic respiratory failure lifestyle and long-term
weight gain in women
Musculoskeletal: Osteoarthritis, low back pain and men. N Engl J Med.
2011;364:2392-404.
Psychosocial effects [PMID: 21696306]
Depression and anxiety 11. Ogilvie RP, Redline S,
Bertoni AG, Chen X,
Social stigmatization Ouyang P, Szklo M, et al.
Actigraphy measured
sleep indices and adipos-
ity: the Multi-Ethnic
health-related quality of life. For in patients who have bariatric Study of Atherosclerosis
(MESA). Sleep. 2016;39:
example, a moderate weight surgery. 1701-8. [PMID:
27306270]
loss of 5%–10% reduces risk for 12. St-Onge MP. Sleep-
type 2 diabetes mellitus (T2DM) A matched cohort analysis using data from the obesity relation: underly-

among at-risk persons, improves Veterans Affairs health care system reported ing mechanisms and
consequences for treat-
that patients undergoing bariatric surgery had ment. Obes Rev.
physical function, reduces sleep
a reduction in mortality of more than 50% dur- 2017;18 Suppl 1:34-39.
apnea, and improves mood and [PMID: 28164452]
ing 14 years of follow-up (4). The Look AHEAD 13. Hanlon EC, Tasali E, Lep-
sexual function. Subgroup analy- (Action for Health in Diabetes) trial, conducted roult R, Stuhr KL, Don-
ses of data from randomized con- in patients with T2DM, showed that those who
check E, de Wit H, et al.
Sleep restriction enhances
trolled trials show evidence of lost at least 10% of their baseline weight had the daily rhythm of
greater health benefits among circulating levels of
improvements in glycemia, blood pressure, tri- endocannabinoid 2-
persons who lose more weight. glyceride levels, and high-density lipoprotein arachidonoylglycerol.
Sleep. 2016;39:653-64.
Data from the United States and cholesterol levels and a 21% reduction in car- [PMID: 26612385]
Europe suggest reduced mortality diovascular disease (5). 14. Nedeltcheva AV, Kilkus
JM, Imperial J, Schoeller
DA, Penev PD. Insuffi-
cient sleep undermines

Screening and Prevention dietary efforts to reduce

adiposity. Ann Intern
Med. 2010;153:435-41.
Should clinicians screen certainty of moderate net [PMID: 20921542]
15. Powell K, Wilcox J, Clo-
patients for overweight and benefit). nan A, Bissell P, Preston
L, Peacock M, et al. The
obesity? How can patients prevent role of social networks in
The U.S. Preventive Services Task obesity?
the development of
overweight and obesity
Force recommends that clinicians Internists can help patients pre- among adults: a scoping
review. BMC Public
offer all patients with a BMI of 30 vent weight gain by reviewing Health. 2015;15:996.
kg/m2 or greater intensive, multi- concurrent medications (Table 1)
[PMID: 26423051]
16. Ludwig J, Sanbonmatsu
component behavioral interven- (7, 8). Medications used to treat L, Gennetian L, Adam E,
Duncan GJ, Katz LF, et al.
tions or refer them to programs inflammatory conditions, psychi- Neighborhoods, obesity,
and diabetes—a random-
that offer such interventions (6). atric disorders, diabetes, and ized social experiment.
The Task Force gave this recom- other conditions may be associ- N Engl J Med. 2011;
365:1509-19. [PMID:
mendation a grade of “B” (high ated with weight gain. Clinicians 22010917]

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 Table 1. Medications Associated With Weight Gain and Alternatives*
Medication Associated With Weight Gain Weight-Neutral or Weight Loss–Promoting Alternative
Rheumatic medications, glucocorticoids Nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic
drugs
Diabetes medications (insulin, sulfonylureas, Metformin, glucagon-like peptide-1 receptor agonists, sodium–glucose
thiazolidinediones, meglitinides) cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors
Medications for schizophrenia and bipolar disorder Ziprasidone (less weight gain)
(clozapine, olanzapine, quetiapine, risperidone,
lithium, valproate)
Antihypertensive medications; ␤-blockers Carvedilol, calcium-channel blockers, angiotensin-converting enzyme
(metoprolol, propranolol) inhibitors, diuretics
Anticonvulsants and agents for chronic pain Zonisamide, topiramate, lamotrigine
(carbamazepine, gabapentin)
Antidepressants (mirtazapine, tricyclics) Bupropion, duloxetine, venlafaxine
Hormonal agents (medroxyprogesterone) Combination estrogen–progesterone oral contraceptives; barrier
methods, intrauterine device

*Data derived in part from reference 8.

17. Jensen MD, Ryan DH,

Apovian CM, Ard JD, can consider substituting medi- vent weight gain in the context of
Comuzzie AG, Donato
KA, et al; American Col-
cations used to treat these condi- decreasing sleep time in the
lege of Cardiology/Amer- tions with alternatives that are United States since approxi-
ican Heart Association
Task Force on Practice weight-neutral or weight loss– mately 1970. Many population-
Guidelines. 2013 AHA/ promoting. Smoking cessation
ACC/TOS guideline for based studies have correlated
the management of increases weight by an average of sleep restriction with weight gain
overweight and obesity
in adults: a report of the 3–5 kg in the first year; however, (12). At least 2 intervention stud-
American College of patients should be encouraged to ies (13, 14) have shown that
Cardiology/American
Heart Association Task prioritize smoking cessation. fewer than 6 hours of sleep per
Force on Practice Guide-
lines and The Obesity
A systematic review of randomized trials that night is associated with loss of
Society. J Am Coll Car-
diol. 2014;63:2985- included weight change as a secondary end lean body mass and increases in
3023. [PMID: point found that tricyclic antidepressants, sul- desire for foods that are high in
24239920]
18. Brownley KA, Berkman fonylureas, and some atypical antidepressants fat and sugar.
ND, Peat CM, Lohr KN, were associated with weight gain. Conversely,
Cullen KE, Bann CM,
et al. Binge-eating disor- drugs that were associated with weight loss in- Several studies have reported
der in adults: a system- cluded metformin, glucagon-like peptide-1
atic review and meta- that a person's social network
analysis. Ann Intern agonists, topiramate, zonisamide, and bupro-
Med. 2016;165:409-20. pion (8). influences weight (15). Most data
[PMID: 27367316] on social networks and obesity
19. Buck DW 2nd, Herbst KL.
Lipedema: a relatively In adults, behaviors associated are observational; however, sev-
common disease with
extremely common mis-
with less weight gain include eat- eral experimental studies have
conceptions. Plast Recon- ing a generally low-fat, high-fiber reported on the effect of “mirror-
str Surg Glob Open.
2016;4:e1043. [PMID: diet that includes more servings ing” of eating and physical activ-
27757353] of fruits, vegetables, nuts, and
20. Pigeyre M, Yazdi FT, Kaur ity behaviors, suggesting that
Y, Meyre D. Recent prog- yogurt; eating fewer meals away social networks can be used to
ress in genetics, epige-
netics and metagenom- from home; limiting intake of red reduce overweight and obesity.
ics unveils the meats, potato products, and One randomized trial reported
pathophysiology of hu-
man obesity. Clin Sci sugar-sweetened beverages; and that modifying the neighborhood
(Lond). 2016;130:943- exercising for 45– 60 minutes per
86. [PMID: 27154742] of residence of low-income
21. Phan-Hug F, Beckmann day (9, 10). Other behaviors that women reduced rates of diabe-
JS, Jacquemont S. Ge-
netic testing in patients affect food intake and energy
tes and severe obesity (16). In
with obesity. Best Pract expenditure and have been
Res Clin Endocrinol addition to social contacts and
Metab. 2012;26:133-43. linked to weight change include
[PMID: 22498244] living environment, published
22. Puhl RM. Language and
job stress, length of commute,
evidence suggests that fetal envi-
Obesity: Putting the and duration and overall quality
Person before the Dis- ronment (maternal obesity, hy-
ease. Medscape. 2014. of sleep (11).
Accessed at www.med- perglycemia, hyperlipidemia) is
scape.com/viewarticle
/828664_2 on 11 Janu-
Sleep, in particular, has become associated with greater risk for
ary 2019. a stronger focus of efforts to pre- childhood obesity.

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 Screening and Prevention... Clinicians should screen for obesity in all 23. Gudzune KA, Doshi RS,
patients and offer or refer them to high-intensity behavioral interven- Mehta AK, Chaudhry ZW,
tions for weight loss. They should also highlight the health benefits of a Jacobs DK, Vakil RM,
et al. Efficacy of commer-
5%–10% weight loss and review their patients' medications for any cial weight-loss pro-
changes that might help with weight reduction. Clinicians should also grams: an updated sys-
evaluate the duration and quality of sleep as part of a weight loss tematic review. Ann
Intern Med. 2015;162:
evaluation. 501-12. [PMID:
25844997]
24. Johnston BC, Kanters S,
Bandayrel K, Wu P, Naji
CLINICAL BOTTOM LINE F, Siemieniuk RA, et al.
Comparison of weight
loss among named diet
programs in overweight
and obese adults: a
meta-analysis. JAMA.
Diagnosis 2014;312:923-33.
[PMID: 25182101]
25. Catenacci VA, Pan Z,
How do clinicians diagnose occurs with aging. BMI can also Ostendorf D, Brannon S,
obesity? be misleading in persons with Gozansky WS, Mattson
MP, et al. A randomized
The 2013 guideline on obesity very high muscle mass (for exam- pilot study comparing
ple, elite athletes); these persons zero-calorie alternate-day
treatment from the American fasting to daily caloric
Heart Association, the American may have high BMI but no excess restriction in adults with
obesity. Obesity (Silver
College of Cardiology, and The risk for weight-related metabolic Spring). 2016;24:1874-
Obesity Society (AHA/ACC/TOS) complications. Women naturally 83. [PMID: 27569118]
26. Trepanowski JF, Kroeger
recommends using BMI to iden- have higher adiposity than men CM, Barnosky A, Klempel
MC, Bhutani S, Hoddy
tify adults at increased risk for and often carry excess weight in KK, et al. Effect of
morbidity (BMI ≥25 kg/m2) and the thighs and/or buttocks, but alternate-day fasting on
weight loss, weight
mortality (BMI ≥30 kg/m2) (17). In this does not increase risk for dia- maintenance, and cardio-
protection among meta-
the general population, BMI cor- betes or cardiovascular disease. bolically healthy obese
relates well with total adiposity Increased metabolic risk in Afri- adults: a randomized
clinical trial. JAMA Intern
and with morbidity and mortality. can American patients starts at a Med. 2017;177:930-8.
The accepted definitions of over- BMI of approximately 27 kg/m2, [PMID: 28459931]
27. Carter S, Clifton PM,
weight and of obesity classes 1, compared with 25 kg/m2 in white Keogh JB. Effect of inter-
mittent compared with
2, and 3 are 25–29.9 kg/m2, 30 – patients. Conversely, increased continuous energy re-
34.9 kg/m2, 35–39.9 kg/m2, and metabolic risk in East Asian and stricted diet on glycemic
control in patients with
40.0 kg/m2 or greater, respec- South Asian patients starts at a type 2 diabetes. A ran-
tively. Class 3 obesity is referred BMI of approximately 23 kg/m2. domized noninferiority
trial. JAMA Netw Open.
to as “severe” obesity, replacing Measures of metabolic health 2018;1:e180756.
28. Tsai AG, Fabricatore AN,
the earlier term “morbid.” Class 2 (blood glucose levels, blood Wadden TA, Higgin-
pressure, lipid levels), along with botham AJ, Anderson A,
obesity with concomitant weight- Foreyt J, et al. Readiness
related comorbidity is referred to BMI and waist circumference, redefined: a behavioral
task during screening
as “severe obesity equivalent.” help to prioritize the importance predicted 1-year weight
All BMI categories have matching of weight loss for an individual loss in the Look AHEAD
study. Obesity (Silver
diagnosis codes. patient. Spring). 2014;22:1016-
23. [PMID: 24151217]
When and how should 29. Heymsfield SB, Wadden
When can BMI be misleading in TA. Mechanisms, patho-
terms of health risk? clinicians measure waist physiology, and manage-
ment of obesity. N Engl J
In clinical encounters, BMI is circumference? Med. 2017;376:254-66.
[PMID: 28099824]
most likely to be misleading by BMI is an estimate of total adipos- 30. Leibel RL, Seeley RJ,
causing underestimation of the ity but does not reflect a patient's Darsow T, Berg EG, Smith
SR, Ratner R. Biologic
health risk associated with a distribution of excess weight. In responses to weight loss
and weight regain: re-
given weight. Specifically, pa- those with a BMI less than 35 kg/ port from an American
tients with low muscle mass are m2, waist circumference can pro- Diabetes Association
research symposium.
more likely to have metabolic vide an additional estimate of Diabetes. 2015;64:2299-
309. [PMID: 26106187]
complications of weight at a cardiometabolic risk. Central adi- 31. Sumithran P, Proietto J.
lower BMI (“sarcopenic obesity”). posity correlates well with visceral The defence of body
weight: a physiological
Sarcopenic obesity is more com- adiposity, which elevates risk for basis for weight regain
mon in older patients, due in part diabetes, hypertension, and nonal- after weight loss. Clin Sci
(Lond). 2013;124:231-
to the loss of muscle mass that coholic fatty liver disease. Waist 41. [PMID: 23126426]

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 circumference is the best proxy for assessment of dietary patterns (for
visceral adiposity that can be rou- example, a 24-hour diet recall),
tinely measured in clinical settings. including intake of sugar-
It should be measured at the top sweetened beverages, processed
of the iliac crests in a horizontal foods, and specific foods that are
32. American Medical Associ- plane after the patient exhales fol- problematic for the patient, as well
ation. Proceedings of the
2013 Annual Meeting of lowing a normal breath. A circum- as late-night eating. Internists
the House of Delegates.
17 November 2013. ference of 35 in (88 cm) or more should inquire about frequency,
Accessed at www.ama for women and 40 in (102 cm) or duration, and intensity of exercise
-assn.org/house
-delegates/annual more for men is considered ele- and any barriers to it. The medical
-meeting/proceedings history and review of systems
-2013-annual-meeting vated. The 2013 AHA/ACC/TOS
-house-delegates on 11 guideline noted that the greater should focus on major weight-
January 2019.
33. Sumithran P, Prender- the waist circumference, the related comorbid conditions. All
gast LA, Delbridge E,
greater the risk for diabetes, car- patients should be screened for
Purcell K, Shulkes A,
Kriketos A, et al. Long- diovascular disease, and all-cause obstructive sleep apnea.
term persistence of hor-
monal adaptations to death.
weight loss. N Engl J
The important elements of the
Med. 2011;365:1597- What elements of the history physical examination in patients
604. [PMID: 22029981]
34. Srivastava G, Apovian and physical examination are with obesity include vital signs
CM. Current pharmaco-
therapy for obesity. Nat important in patients with (BMI, resting heart rate and
Rev Endocrinol. 2018;
obesity? blood pressure, oxygen satura-
14:12-24. [PMID:
tion) and a cardiopulmonary ex-
29027993] The history of the present illness
35. Smith SR, Weissman NJ, amination (Table 3). Finally, the
Anderson CM, Sanchez should include a weight history
M, Chuang E, Stubbe S, initial assessment should include
et al; Behavioral Modifi-
(for example, highest and lowest
screening for stress or emotional
cation and Lorcaserin for weight in adulthood), with con-
Overweight and Obesity eating. Patients who report stress
Management (BLOOM) sideration of life events associ-
Study Group. Multi- or emotional eating should un-
ated with significant weight gain
center, placebo- dergo formal screening for binge-
controlled trial of lorca- (such as pregnancy) (Table 2).
serin for weight eating disorder, an obesity-related
management. N Engl J Internists should inquire about
Med. 2010;363:245-56.
but distinct diagnosis with its own
previous weight loss attempts,
[PMID: 20647200] set of behavioral and pharmaco-
36. Bohula EA, Wiviott SD, with a focus on participation in
McGuire DK, Inzucchi SE, logic treatments (18).
Kuder J, Im K, et al; high-intensity programs (as de-
CAMELLIA–TIMI 61 Steer- fined in the 2013 AHA/ACC/TOS What are secondary causes of
ing Committee and
Investigators. Cardiovas- guideline), successful efforts obesity?
cular safety of lorcaserin
in overweight or obese
(those resulting in weight loss of Hypothyroidism, hypercortiso-
patients. N Engl J Med. ≥5%–10%), and the patient's cur- lism, and traumatic brain injury
2018;379:1107-17.
[PMID: 30145941] rent interest in losing weight. The are rare causes of obesity in
clinician should include systematic adults. More common secondary

Table 2. Important Elements of History in Patients With Obesity

Category Specific Questions
Presence of weight-related comorbidities Examples include diabetes duration and control and presence and severity
of osteoarthritis
Weight loss goals Patient goals; goals from other clinicians (e.g., for total joint replacement);
realistic weight loss goals (may not be a weight goal—for example “health”
or improved functional status)
Weight history Highest and lowest weight in adulthood; previous weight loss attempts,
methods, and results
Diet history 24-hour diet recall; intake of sugar-sweetened beverages and fruits and
vegetables
Psychosocial Family support; emotional eating or binge eating
Physical activity Minutes of moderate to vigorous activity per week; barriers to exercise;
previous experience with exercise
Sleep assessment Screening questions for obstructive sleep apnea; assessment of duration and
quality of sleep (Berlin Questionnaire, Epworth Sleepiness Scale, or STOP-
BANG criteria) and sleep study if symptoms are suggestive

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 Table 3. Physical Examination of Patients With Obesity
Organ/Organ System Physical Finding Associated Condition
Skin Acne/hirsutism Polycystic ovarian syndrome
Acanthosis nigricans Insulin resistance
Striae (>0.4 in [>1 cm], purple); bruising Cushing syndrome
Neck Elevated circumference (≥17 in [≥43 cm] in Obstructive sleep apnea
men, ≥16 in [≥41 cm] in women)
Thyroid Small/firm/nodules/goiter Hypothyroidism
Cardiovascular system Blood pressure/pulse Hypertension, deconditioning
Oxygen saturation (resting and/or ambulatory) Pulmonary hypertension
Cardiac rhythm Atrial fibrillation
S3/S4 gallop Congestive heart failure
Abdomen Waist circumference Abdominal obesity
Hepatomegaly Nonalcoholic fatty liver disease
Extremities Peripheral edema, hyperpigmentation Venous stasis, pulmonary hypertension, congestive
heart failure
Eyes Papilledema Pseudotumor cerebri
Musculoskeletal Proximal muscle weakness Cushing syndrome
Decreased range of motion, deformity Osteoarthritis

causes include inadequate sleep thyroid-stimulating hormone,

and medications that increase liver-associated enzymes, and
appetite or adipose tissue depo- fasting lipids. A sleep study, right
sition. Screening for sleep dura- upper quadrant ultrasonography
37. Gadde KM, Allison DB,
tion and quality and review of (liver or gallbladder), echocardi- Ryan DH, Peterson CA,
concomitant medications should Troupin B, Schwiers ML,
ography, or transvaginal ultra- et al. Effects of low-dose,
be part of an initial evaluation for sonography (ovarian cysts) may controlled-release, phen-
termine plus topiramate
weight management. be indicated in some patients. combination on weight
Testing for Cushing syndrome is and associated comor-
Internists are likely to see pa- not recommended unless there
bidities in overweight
and obese adults (CON-
tients with lipedema, which is are other specific signs and QUER): a randomised,
placebo-controlled,
typically misdiagnosed as obesity symptoms, including proximal phase 3 trial. Lancet.
(19). Lipedema is a clinical diag- muscle weakness, wide purple
2011;377:1341-52.
[PMID: 21481449]
nosis, with disproportionate ac- striae, easy bruising, or unex- 38. Allison DB, Gadde KM,
cumulation of adipose tissue in pected osteoporosis. In patients
Garvey WT, Peterson CA,
Schwiers ML, Najarian T,
the lower extremities, sometimes et al. Controlled-release
with a history of bariatric surgery phentermine/topiramate
described as “adipose tissue leg-
and weight regain, a barium in severely obese adults:
gings” with sparing of the feet a randomized controlled
swallow or contrast upper gastro- trial (EQUIP). Obesity
(no accumulation below the an- (Silver Spring). 2012;20:
intestinal tract radiography is
kles). The prevalence of the dis- 330-42. [PMID:
sometimes needed to confirm 22051941]
ease is not known. It occurs almost 39. Khera R, Murad MH,
the anatomical integrity of the Chandar AK, Dulai PS,
exclusively in women and does not
original surgical procedure. Wang Z, Prokop LJ, et al.
respond to traditional lifestyle Association of pharmaco-
logical treatments for
modification (reduced caloric in- obesity with weight loss
take and increased physical What is the relationship of and adverse events: a
obesity to genetics? systematic review and
activity). meta-analysis. JAMA.
A strong family history of obesity, 2016;315:2424-34.
What laboratory tests or particularly severe obesity, sug-
[PMID: 27299618]
40. Wadden TA, Foreyt JP,
other evaluations should be gests a genetic component. Ge- Foster GD, Hill JO, Klein
S, O’Neil PM, et al.
considered in patients with netics accounts for 40%–75% of Weight loss with naltrex-
one SR/bupropion SR
obesity? the variability in BMI, although combination therapy as
Routine laboratory studies in pa- the rapid rise of severe obesity an adjunct to behavior
modification: the COR-
tients with obesity should include in the United States and other BMOD trial. Obesity
measurement of levels of fasting developed countries in the past (Silver Spring). 2011;19:
110-20. [PMID:
glucose and/or hemoglobin A1c, 45 years is believed to have a 20559296]

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 strong environmental compo- as severe early-onset obesity in
nent. Among children with se- infancy or childhood and may be
vere obesity, 2%–5% of cases are associated with developmental
believed to be related to muta- delay and altered reproductive
41. Torgerson JS, Hauptman tions in the melanocortin-4 re- function (21). Prader–Willi syn-
J, Boldrin MN, Sjöström
L. XENical in the preven-
ceptor (20). No targeted thera- drome is the most common of
tion of diabetes in obese pies are available for any genetic these, presenting with short stat-
subjects (XENDOS) study:
a randomized study of obesity disorder. Several rare ure, small hands and feet, hypo-
orlistat as an adjunct to
lifestyle changes for the
genetic syndromes can cause gonadism, and almond-shaped
prevention of type 2 obesity. These typically present eyes.
diabetes in obese pa-
tients. Diabetes Care.
2004;27:155-61. [PMID:
14693982] Diagnosis... BMI should be used to diagnose obesity and should be
42. Pi-Sunyer X, Astrup A,
Fujioka K, Greenway F, combined with markers of metabolic health (lipids, blood glucose) to
Halpern A, Krempf M, individualize weight-related health risk. Waist circumference should
et al; SCALE Obesity and
Prediabetes NN8022- also be measured in patients with a BMI of 25–34.9 kg/m2 to assess for
1839 Study Group. A abdominal obesity, which increases health risk. The history and physical
randomized, controlled examination should focus primarily on weight-related conditions,
trial of 3.0 mg of liraglu-
tide in weight manage- weight trajectory, and previous weight loss attempts. Laboratory testing
ment. N Engl J Med. should include screening for diabetes, nonalcoholic fatty liver disease,
2015;373:11-22. [PMID:
26132939] thyroid dysfunction, and dyslipidemia.
43. Mechanick JI, Youdim A,
Jones DB, Timothy
Garvey W, Hurley DL,
Molly McMahon M, et al. CLINICAL BOTTOM LINE
Clinical practice guide-
lines for the periopera-
tive nutritional, meta-
bolic, and nonsurgical
support of the bariatric
surgery patient—2013
update: cosponsored by
Treatment
American Association of
Clinical Endocrinologists,
How should clinicians counsel benefits. In its 2011 decision to
the Obesity Society, and patients about their weight? reimburse primary care providers
American Society for
Metabolic & Bariatric Appropriate language is impor- for obesity treatment, the Centers
Surgery. Surg Obes Relat
tant in discussions of obesity with for Medicare & Medicaid Services
Dis. 2013;9:159-91.
[PMID: 23537696] patients. Use of people-first lan- recommended using a “5A” ap-
44. Sakran N, Sherf-Dagan S,
Blumenfeld O, Romano- guage (for example, “patients proach: Assess (weight and risk
Zelekha O, Raziel A, with obesity” rather than “obese factors), Advise (weight loss, per-
Keren D, et al. Incidence
and risk factors for mor- patients”) is recommended (22). sonalize the recommendation to
tality following bariatric
surgery: a nationwide Several studies have reported the patient), Agree (on a target for
registry study. Obes that patients prefer that clinicians behavior change), Assist (with a
Surg. 2018;28:2661-9.
[PMID: 29627947] use the terms “weight” or “weight referral), and Arrange (follow-up).
45. Inaba CS, Koh CY,
Sujatha-Bhaskar S, Silva
problem” rather than “obesity”
JP, Chen Y, Nguyen DV, when discussing the topic. Most An algorithm published in the
et al. One-year mortality
patients with overweight and 2013 AHA/ACC/TOS guideline
after contemporary lapa-
roscopic bariatric surgery: obesity know that weight loss will can assist patients and clinicians
an analysis of the Bariat-
ric Outcomes Longitudi- lead to improved health. Thus, in selecting an intervention. The
nal Database. J Am Coll
rather than simply advising algorithm recommends a com-
Surg. 2018;226:1166-
74. [PMID: 29551698] weight loss, internists should ask prehensive program of lifestyle
46. Mulla CM, Middelbeek
RJW, Patti ME. Mecha- for permission to discuss weight modification for patients who
nisms of weight loss and and, if it is granted, ask patients have a medical indication for
improved metabolism
following bariatric sur- what treatment options they may weight loss and are considered
gery. Ann N Y Acad Sci.
2018;1411:53-64. want to pursue. Many patients ready to initiate treatment (17).
[PMID: 28868615] present to their physician with Patients who do not achieve and
47. Courcoulas AP, Yanovski
SZ, Bonds D, Eggerman unrealistic weight loss goals. maintain weight loss of at least
TL, Horlick M, Staten MA, 5% should be reevaluated, and
et al. Long-term out-
Thus, internists should also coun-
comes of bariatric sur- sel patients on the health benefits treatment intensification should
gery: a National Insti-
tutes of Health of modest weight loss (5%–10%) be considered. Medications are
symposium. JAMA Surg.
2014;149:1323-9.
while acknowledging that greater an option for patients with a BMI
[PMID: 25271405] weight loss leads to greater health of 30 kg/m2 or greater or those

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 Table 4. Key Components of a Comprehensive Lifestyle Modification Program to Achieve and Maintain Weight
Loss of 5%–10%*
Component Weight Loss Maintenance
Frequency, duration, and type ≥14 visits in the first 6 mo, group or Monthly or more frequent contact with a
of treatment contact individual contact, with personalized trained interventionist for ≥1 y
feedback from a trained interventionist
Web-based or telephone contact (with
personalized feedback) is an acceptable
alternative, although less weight is lost
Dietary prescription Reduced-calorie diet (about 1200–1500 kcal Continued consumption of a reduced-calorie
for women; about 1500–1800 kcal for diet to maintain reduced body weight
men); using any evidence-based diet to
create an energy deficit of 500–1000
kcal/d
Physical activity prescription ≥150 min of moderately vigorous activity 200–300 min of moderately vigorous activity
(including strength training)/wk (including strength training)/wk
Behavior modification Daily monitoring of food intake and physical Occasional to daily monitoring of food intake
activity using paper or electronic records; and physical activity; twice-weekly to daily
weekly weight monitoring; structured weight monitoring; continued curriculum
curriculum of behavior change; regular of behavior change, including relapse
feedback from an interventionist prevention and individualized problem
solving

*From 2013 AHA/ACC/TOS [American College of Cardiology/American Heart Association Task Force on Practice Guidelines and
The Obesity Society] Guideline for Management of Overweight and Obesity in Adults.
48. Arterburn D, Wellman R,
Emiliano A, Smith SR,
2
with a BMI of 27 kg/m or greater tact for maintenance of weight Odegaard AO, Murali S,
et al; PCORnet Bariatric
and a comorbid condition. Sur- loss. The guideline also states Study Collaborative.
Comparative effective-
gery is an option for patients with a that interventions must provide ness and safety of bariat-
BMI of 40 kg/m2 or greater or individualized feedback to the ric procedures for weight
loss: a PCORnet cohort
those with a BMI of 35 kg/m2 or participant and that the coun- study. Ann Intern Med.
greater and a comorbid condition. selor must be a trained interven- 2018;169:741-50.
[PMID: 30383139]
What defines lifestyle tionist (for example, a registered 49. Schauer PR, Bhatt DL,
Kirwan JP, Wolski K,
modification for obesity? dietitian or a layperson with spe- Aminian A, Brethauer SA,
cific training in weight manage- et al; STAMPEDE Investi-
The AHA/ACC/TOS guideline gators. Bariatric surgery

defines a comprehensive lifestyle ment protocols). High-intensity versus intensive medical

therapy for diabetes -
intervention as including pre- programs result in weight loss of 5-year outcomes. N Engl
5%–10% in the first 3– 6 months. J Med. 2017;376:641-
scription of a reduced-calorie 51. [PMID: 28199805]
diet, at least 150 minutes of The guideline also states that 50. Salminen P, Helmiö M,
Ovaska J, Juuti A,
moderate-intensity physical activ- telephone or online intervention Leivonen M, Peromaa-

ity per week (with 200 –300 min- is an acceptable alternative to Haavisto P, et al. Effect of
laparoscopic sleeve gas-
utes for maintenance of weight in-person intervention, provided trectomy vs laparoscopic
Roux-en-Y gastric bypass
loss per week), and behavioral that the participant interacts with on weight loss at 5 years
strategies to achieve diet and a trained interventionist and re- among patients with
morbid obesity: the
physical activity targets (Table 4) ceives individualized feedback SLEEVEPASS randomized
clinical trial. JAMA.
(17). Behavior modification incor- on their efforts. Weight loss was 2018;319:241-54.
porates a set of principles and noted to be slightly lower in tele- [PMID: 29340676]
51. Courcoulas AP, King WC,
practices, which include self- phone and online programs than Belle SH, Berk P, Flum
DR, Garcia L, et al. Seven-
monitoring, goal setting, prob- with in-person interventions. The year weight trajectories
lem solving, environmental guideline also stated that some and health outcomes in
the Longitudinal Assess-
modification, social support, commercial weight loss pro- ment of Bariatric Surgery
and relapse prevention. grams with published evidence (LABS) study. JAMA Surg.
2018;153:427-34.
of safety and efficacy in peer- [PMID: 29214306]
The AHA/ACC/TOS guideline 52. King WC, Chen JY,
reviewed journals can also be Mitchell JE, Kalarchian
states that the standard for high-
prescribed. MA, Steffen KJ, Engel
intensity lifestyle intervention is at SG, et al. Prevalence of
alcohol use disorders
least 14 visits (group or individual An updated systematic review of the efficacy of before and after bariatric
treatment) in the first 6 months, surgery. JAMA. 2012;
commercial weight loss programs that was 307:2516-25. [PMID:
followed by at least monthly con- published in 2015 reported that Weight 22710289]

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 Watchers, Jenny Craig, Nutrisystem, Health ing feature of several popular
Management Resources, Optifast, Medifast, diets is consumption of foods
Atkins, and SlimFast all had published evi- that are low in energy density
dence of efficacy (23). (number of calories per gram of
What dietary strategies are food) and high in dietary fiber.
used in lifestyle modification? Thus, a plan that includes high-
Patients with obesity should seek quality lean protein sources, veg-
to create a negative energy bal- etables and fruits, and some
ance by reducing caloric intake healthy fats (such as nuts and av-
by 500 –1000 kcal/d. This should ocados) and limits intake of re-
lead to an initial weight loss of fined carbohydrates should be
1–2 lb (0.5–1 kg) per week the initial choice for most pa-
(quickly at first, with slowing over tients. Patient preference should
the first several months). Ideally, be incorporated within these
the reduction in caloric intake general guidelines. Patients may
should be accompanied by a choose to follow meal plans
gradual increase in physical activ- ranging from a vegetarian diet to
ity. Calorie restriction is the prin- a very-low-carbohydrate keto-
cipal method for inducing weight genic (“keto”) diet. Because of
loss because most patients find it metabolic adaptations to weight
easier to reduce their food intake loss, any diet that is successful
by 500 –1000 kcal/d than to in- must be sustained over time.
crease energy expenditure by an Published studies suggest that
equivalent amount. For example, dietary adherence, self-
to achieve a 500-kcal/d energy monitoring, and attendance at
deficit, a patient can either elimi- treatment visits are more impor-
nate two 20-ounce sugar- tant than diet composition in de-
sweetened drinks or walk 5 miles. termining success in weight loss.
Patients and clinicians can set a A meta-analysis of 48 randomized trials (n =
daily calorie target for weight 7286) showed that all structured diets were
loss by using easily accessible more effective than no diet at 6 and 12
equations to estimate daily en- months. This study also reported that low-
ergy expenditure (such as Harris– carbohydrate diets (Atkins, South Beach, Zone)
Benedict or Mifflin–St. Jeor) and resulted in slightly greater weight loss in the
53. Neovius M, Bruze G,
then subtracting 500 –1000 kcal first 6 months (2–3 kg) than plans with moder-
Jacobson P, Sjöholm K,
Johansson K, Granath F, from this value. Clinicians should ate macronutrient content (55%– 60% carbo-
et al. Risk of suicide and hydrate), but differences were small at 12
non-fatal self-harm after remember that persons with
bariatric surgery: results months or later (24).
from two matched cohort
overweight and obesity signifi-
studies. Lancet Diabetes cantly underestimate caloric in- What alternative dietary
Endocrinol. 2018;6:197-
207. [PMID: 29329975] take in free-living environments. strategies are available?
54. Salehi M, Vella A,
McLaughlin T, Patti ME.
Therefore, adults who weigh less
than 250 lb (113.4 kg) are com- Meal-replacement diets
Hypoglycemia after gas-
tric bypass surgery: cur-
monly prescribed 1200 –1500 A meal replacement is defined as
rent concepts and contro-
versies. J Clin Endocrinol kcal/d, whereas those who weigh a shake or bar that has approxi-
Metab. 2018;103:2815-
250 lb or more are prescribed mately 200 calories, at least
26. [PMID: 30101281]
55. Garvey WT, Mechanick JI, 1500 –1800 kcal/d as a starting 15–20 g of protein, no more than
Brett EM, Garber AJ,
Hurley DL, Jastreboff AM, point. Calorie targets are then 5 g of sugar, and at least 5 g of
et al; Reviewers of the
adjusted on the basis of ob- fiber and is supplemented with
AACE/ACE Obesity Clini-
cal Practice Guidelines. served weight loss. all essential vitamins and miner-
American Association of als. Meal replacements facilitate
Clinical Endocrinologists
and American College of Which diet is best for portion control and calorie
Endocrinology Compre- long-term weight loss?
hensive Clinical Practice
counting and can be helpful for
Guidelines for Medical Most evidence suggests that di- patients who do not have ade-
Care of Patients With
Obesity. Endocr Pract. ets with different macronutrient quate time for food preparation.
2016;22 Suppl 3:1-203. content produce similar weight Data from randomized trials sug-
[PMID: 27219496] doi:10
.4158/EP161365.GL loss over the long term. A unify- gest that a calorie target that in-

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 cludes substituting 2 meals per ical activity for ≥1 week) and then of obesity should understand
day with a meal replacement follow up to see whether they that, if successful, pharmacother-
leads to greater weight loss than adhered to the plan. apy will be needed on a long-
the same calorie target using term basis. Weight is typically,
A secondary analysis of data from the multi-
only conventional foods. regained when medication use
center Look AHEAD trial reported that study
participants who kept a more detailed food re-
is stopped (35). The FDA indica-
Intermittent fasting
cord (that is, wrote more words) lost more tion for pharmacotherapy is a
Intermittent fasting has increased
weight in the first 12 months than those who BMI of 30 kg/m2 or greater or a
in popularity as an alternative to
kept less detailed records (28). BMI of 27 kg/m2 or greater with
the traditional approach of daily
caloric restriction. The advantage a weight-related comorbid con-
Why is it difficult to maintain dition, such as diabetes, hyper-
of this approach is that patients weight loss, and what improves
can look forward to several days of tension, or obstructive sleep
less restricted eating each week
long-term results? apnea. Pharmacotherapy is con-
rather than having to face daily Most patients “plateau” after the traindicated in pregnancy, and
hunger. At least 3 randomized tri- first 3– 6 months of weight loss. women of childbearing age
als (25–27) have shown that inter- On average, patients regain one should be advised to avoid
mittent or modified fasting results third of lost weight over the ensu- pregnancy while using these
in weight loss similar to that of con- ing year, with continued regain medications. The goal of phar-
ventional daily energy restriction. over time. Weight loss leads to macotherapy is weight loss of
One of the 3 trials (27) included adaptations in appetite and en- 5% or more over the first 3– 6
only patients with T2DM and ergy expenditure (29). The re- months. If this target is not
showed a similar effect of daily and ductions in energy expenditure reached, use of the medication
intermittent energy restriction on are disproportionate to the should be stopped. Postmarket-
glycemic control. amount of weight and lean body ing clinical trials to ensure safety
mass lost (30). Weight loss also of long-term use of currently ap-
What is the role of exercise in leads to increases in hunger sig-
weight loss and maintenance? proved agents for obesity have
naling. These adaptations seem been completed or are ongoing.
Regular exercise has many im- to persist over the long term (31),
portant health benefits. However, reinforcing the idea that obesity, In the first of the postmarketing trials to be
exercise alone or combined with once established, is a chronic published, 12 000 patients with elevated car-
calorie restriction results in addi- metabolic disease, with a physio- diovascular risk were randomly assigned to
tional weight loss of only 1–3 kg. logic basis for weight regain (32). receive lorcaserin or placebo and were fol-
Data from randomized controlled lowed for a median of 3.3 years. Weight loss
trials and observational studies To improve the chances of main- was 4 kg in the lorcaserin group versus 2.1 kg
suggest that exercise is more im- taining weight loss, the AHA/ in the placebo group. Patients randomly as-
portant for mainting weight loss ACC/TOS guideline recom- signed to lorcaserin had slightly greater im-
than for initial induction. Within a mends monthly or more frequent provements in cardiovascular disease risk fac-
set number of minutes of exer- face-to-face or telephone con- tors. Rates of a composite cardiovascular
cise per week, the combination tact, 200 –300 minutes of physical outcome were similar between groups (36).
of aerobic and resistance training activity per week, weekly or more
has greater health benefits than frequent monitoring of body Several randomized trials have
doing only 1 form of exercise. weight, and continued consump- shown that the addition of high-
How can clinicians assess tion of a reduced-calorie diet. intensity lifestyle modification
readiness for weight loss? programs leads to approxi-
Among persons maintaining weight loss of
mately double the weight loss
The AHA/ACC/TOS guideline 9%, subjective markers of hunger and blood
seen with pharmacotherapy
recommends that clinicians ask, levels of ghrelin were higher 1 year after
“How prepared are you to make weight loss plateaued than with baseline mea- alone. Thus, clinicians should ad-
changes in your diet, to be more sures (33). vise patients to pursue both treat-
physically active, and to use be- ments together. Currently, 5
When is it appropriate to use agents are FDA-approved for
havior change strategies such as
recording your weight and food medications to treat obesity? long-term treatment of over-
intake?” A practical approach to Pharmacotherapy for obesity can weight and obesity (Appendix
assess readiness may be to ask be considered for patients who Table 1, available at Annals.org).
patients to take initial steps to- have not met weight loss goals However, high cost, moderate
ward behavior modification for with lifestyle modification alone weight loss, and lack of insurance
weight loss (for example, self- (7, 34). Patients wanting to start coverage have limited uptake of
monitoring food intake and phys- use of a medication for treatment the newer medications.

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 What medications are online training program (www pression. Naltrexone, through
prescribed for weight loss? .qsymiarems.com). The adverse inhibition of an autoregulatory
effect of greatest concern is the loop in the hypothalamus, en-
Phentermine teratogenicity of topiramate and hances the appetite suppressant
Because of its low cost, phenter- thus the need for highly effective effect of bupropion (40). In the
mine is the most commonly used contraception in women of 2016 network meta-analysis (39),
medication for weight loss in the childbearing age. bupropion–naltrexone had inter-
United States, accounting for mediate probability of achieving
more than 80% of prescriptions. Lorcaserin
a 5% weight loss and the second-
Phentermine is not FDA- Lorcaserin (Belviq [Eisai]) is an
highest probability of adverse
approved for long-term use. How- agonist of the 5-HT2C receptor in
effects. The most common ad-
ever, the current clinical guideline the brain, which is involved in
verse effects include nausea, diz-
on pharmacotherapy (7) suggests appetite regulation (35). Unlike
ziness, changes in bowel habits,
that long-term use may be appro- selective serotonin reuptake in-
and insomnia. Contraindications
priate if the patient achieves and hibitors (such as fluoxetine and
include seizure disorders, end-
maintains a clinically significant sertraline), lorcaserin does not
stage renal disease, eating disor-
weight loss (generally interpreted significantly affect mood. It was
ders, any current opiate use or
as ≥5%), blood pressure and designed specifically to avoid
withdrawal, or any risky alcohol
pulse remain normal, no contrain- serotonin agonism in the heart,
use.
dications to phentermine use exist which was believed to be the un-
at the start of therapy or develop derlying mechanism of the car- Orlistat
during treatment, and the patient diac valve disease seen in some Orlistat is available over the
has been informed of the agents patients who received dexfenflu- counter in a low dose (60 mg 3
that are FDA-approved for long- ramine or “fen-phen” in the times daily; alli [GlaxoSmithK-
term use. 1990s. In the 2016 network meta- line]) and is also available in a
analysis (39), lorcaserin had the prescription-strength dose (120
Phentermine–topiramate second-lowest probability of mg 3 times daily; Xenical
extended-release
achieving a 5% weight loss but [Roche]). Orlistat has published
Phentermine–topiramate also the lowest risk for adverse data on safety and efficacy for as
extended-release (ER) (Qsymia effects. Common adverse effects long as 4 years (41). In the 2016
[VIVUS]) is a once-daily formula- include headache; upper respira- network meta-analysis (39), orli-
tion of 2 medicines previously tory infection; musculoskeletal stat had the lowest probability of
approved for other indications pain; and, in patients with diabe- a 5% weight loss and the second-
that both cause weight loss. tes, hypoglycemia. Contraindica- lowest probability of adverse ef-
Phentermine–topiramate ER tions include systolic heart fects. The main adverse effects of
combines these drugs in lower failure, mitral (moderate or orlistat (such as oily stools and
doses, with the goal of fewer greater) or aortic (mild or fecal discharge) are related to its
stimulant effects (phentermine), greater) regurgitation, stage 4 or mechanism of action of inhibiting
fewer adverse cognitive effects
5 chronic kidney disease, and intestinal lipase, leading to a 30%
(topiramate), and greater weight
high-grade heart block. Caution decrease in dietary fat absorp-
loss efficacy (37, 38). A 2016 sys-
should be used when lorcaserin tion. Patients who use orlistat
tematic review and network
is prescribed to patients receiv- should take fat-soluble vitamin
meta-analysis of the 5 available
ing any other medications that supplements (A, D, E, and K) 2–3
agents approved for long-
increase serotonin, given the hours separated from any dose.
term use (39) reported that
hypothetical risk for serotonin Caution should be used in pa-
phentermine–topiramate ER had
syndrome. tients with malabsorption or
the highest probability of achiev-
nephrolithiasis and those receiv-
ing a 5% weight loss. Common Bupropion–naltrexone
ing warfarin or immunosuppres-
adverse effects include pares- Bupropion–naltrexone (Contrave
sant medications that require reli-
thesias, change in taste, dry [Nalpropion Pharmaceuticals]) is
able absorption.
mouth, constipation, and insom- another combination agent in
nia. Contraindications include which both components are Liraglutide
nephrolithiasis, uncontrolled already approved for other indi- Liraglutide is an injectable
hypertension, or resting tachy- cations and have existing safety agonist of the glucagon-like
cardia. Clinicians who want to records. Bupropion generally peptide-1 receptor, which slows
prescribe phentermine–topira- leads to modest weight loss gastric emptying and reduces
mate ER must complete a brief when used for treatment of de- appetite through central nervous

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 system actions. Liraglutide was need for regular follow-up to more effective than sleeve gas-
previously approved in a 1.8-mg monitor weight and nutritional trectomy in terms of weight loss
dose for T2DM (Victoza [Novo status and the need to take spe- and improvements in glucose
Nordisk]). It was approved by the cialized vitamin supplements for control in patients with T2DM.
FDA in 2014 at a higher dose (3.0 the rest of their life. The 30-day Although glucose levels initially
mg) for treatment of obesity with- mortality rate for bariatric surgery improve dramatically in many
out diabetes (Saxenda [Novo is approximately 0.1% (44, 45). patients with T2DM, hemoglobin
Nordisk]) (42). In the 2016 net- A1c levels increase gradually in
work meta-analysis (39), liraglu- Most bariatric procedures in the the first 5 years after surgery.
tide had the second-highest United States are comprise gas- Epidemiologic and prospective
probability of resulting in a 5% tric bypass or sleeve gastrec- nonrandomized data show an
weight loss and the highest risk tomy. The laparoscopic gastric initial increase in mortality rates
for adverse events. The most band is now rarely offered be- in the immediate postoperative
common adverse effects include cause of smaller weight losses, period, followed by a progres-
nausea, vomiting, constipation or the need for adjustment, and sive reduction in mortality in sur-
diarrhea, and dyspepsia. Contra- the potential for mechanical gical patients compared with
indications include a history of complications. patients with severe obesity who
medullary thyroid carcinoma, a do not have surgery (4, 47). The
In gastric bypass, the stomach is
family history of multiple endo- risk for perioperative death
transected proximally, and the
crine neoplasia type 2, or any after weight loss surgery is simi-
mid-jejunum is also transected
history of pancreatitis. Caution lar to that with laparoscopic
and connected to the proximal
should be used in patients with cholecystectomy.
stomach pouch. The remaining
chronic kidney disease and those distal stomach, duodenum, and In an analysis of administrative data from 41
with gastrointestinal motility dis- proximal jejunum are anasto- health systems in the United States (gastric by-
orders. Liraglutide is significantly mosed to form a “blind limb,” pass n = 32 208; sleeve gastrectomy n =
more expensive than the other which ends proximally in the 29 693), weight loss at 1 year was 31.2% for
oral antiobesity agents. closed-off stomach and is no lon- gastric bypass and 25.2% for sleeve gastrec-
ger part of the active digestive tomy. Weight loss at 5 years was 25.5% and
How safe and effective is
process. Gastric bypass restricts 18.8%, respectively. Rates of major adverse
bariatric surgery? events at 30 days were 5.0% for gastric bypass
Bariatric (weight loss) surgery is food intake, and results in partial
and 2.6% for sleeve gastrectomy (48).
indicated for patients with a BMI malabsorption, changes in
appetite-regulating hormones In the STAMPEDE (Surgical Treatment and Med-
of 40 kg/m2 or greater or those ications Potentially Eradicate Diabetes Effi-
with a BMI of 35 kg/m2 or greater (such as ghrelin), and changes in
bile acids and gut microbiota, all ciently) randomized trial, 150 patients with
and at least 1 serious weight- T2DM were randomly assigned to intensive
related comorbid condition, such of which are believed to contrib-
medical treatment or bariatric surgery (sleeve
as T2DM, obstructive sleep ap- ute to weight loss (46). gastrectomy or gastric bypass). After 5 years,
nea, or osteoarthritis of the hip or weight loss was 21%–23% in the surgically
In sleeve gastrectomy, approxi-
knee (43). Before having surgery, treated group versus 5% in the medical treat-
mately 75% of the stomach is re-
patients ideally should make sus- ment group. Five percent of patients in the med-
sected, but the remainder of the ical treatment group achieved the primary out-
tained attempts at weight loss intestinal tract stays intact. come (hemoglobin A1c level <6%) compared
with high-intensity lifestyle modi- Weight loss is achieved primarily with 29% in the surgically treated group (49).
fication programs, structured by food restriction, although the
meal plans, and/or pharmaco- The SLEEVEPASS (Sleeve vs Bypass) trial, con-
removal of endocrine-rich gastric ducted in Finland, randomly assigned 240 pa-
therapy (17). The standard of tissue may also contribute. tients with severe obesity (mean BMI, 45.9 kg/
care for patients considering
What is the comparative m2) to laparoscopic sleeve gastrectomy or gastric
weight loss surgery is to be eval- bypass. Weight loss at 5 years was 49% in the
uated for medical safety and psy- effectiveness of the various
sleeve gastrectomy group and 57% in the gastric
chological appropriateness and a types of bariatric surgery? bypass group, which corresponded to reduc-
course of presurgery education. Bariatric surgery is the most ef- tions in BMI of 10.8 and 13 units, respectively.
Patients should be well informed fective treatment available for No differences were seen in health-related qual-
of the risks and benefits of producing long-term weight loss ity of life or major complications. No patients
weight loss surgery, including the and improving weight-related died of a surgical complication during the 5
small probability of long-term comorbid conditions, especially years of the trial (50).
adverse outcomes. In addition, glucose levels in patients with The LABS (Longitudinal Assessment of Bariat-
patients must be informed of the T2DM. Gastric bypass is slightly ric Surgery) study provided data from the lon-

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 gest follow-up of a U.S. population of weight clude small increases in alcohol good nutritional status. In addi-
loss surgery patients. Seven-year data showed misuse and suicide (52, 53). In tion to screening for micronutri-
a weight loss of 28.4% for gastric bypass (in- addition, gastric bypass patients ent deficiencies, the American
cluding a 3.9% gain from nadir at year 3) are at risk for postsurgery hypo- Society for Metabolic and Bariat-
(51). glycemia (54). ric Surgery recommends screen-
What are complications of What is involved in long-term ing for osteoporosis at 2 years
bariatric surgery? follow-up after bariatric after surgery in gastric bypass
Bariatric surgery can have both surgery? patients (55). Increased physical
early (first 30 days) and late com- activity after bariatric surgery
Patients undergoing weight loss
plications. Internists are more surgery must be prepared to un- helps to preserve lean body mass
likely to see late complications. dertake regular follow-up (sev- and leads to better long-term
The most common early compli- eral times in the first year, then at weight loss. Prescription medica-
cations are nausea, vomiting, least annually) after bariatric sur- tions for weight loss may help
thromboembolic disease, anas- gery, with the goal of maintaining some patients who do not meet
tomotic leak (gastric sleeve), their weight loss and maintaining weight loss goals after surgery.
bleeding, or obstruction. Nutri-
tional deficiencies (for example,
iron or vitamin D) can occur over
Treatment... Clinicians should use person-first language when discuss-
the long term but can be pre- ing weight with patients. They should encourage patients to monitor
vented by routine monitoring, a their food and caloric intake. Patients may choose to follow any eating
balanced diet, and lifelong use plan that includes lean proteins, fruits and vegetables, and legumes
of specialized bariatric multivita- and that minimizes refined carbohydrates. Any dietary modifications
mins (Appendix Table 2, avail- that are successful for weight loss must be maintained indefinitely. Exer-
able at Annals.org). Anastomotic cise is more useful for maintenance of weight loss than initial induction.
Pharmacotherapy can be considered for selected patients and must be
ulcer or stenosis can occur early used on a long-term basis to maintain weight loss and health benefits.
or late in patients undergoing Bariatric surgery is the most effective treatment for severe obesity. Sur-
gastric bypass. Nonsteroidal gery has the potential to greatly improve overall health and is associ-
anti-inflammatory medications ated with less common but significant long-term risks. It also requires a
and nicotine use in any form commitment to lifelong visits and monitoring.
are contraindicated for life after
gastric bypass due to ulcer risk.
Uncommon complications in-
CLINICAL BOTTOM LINE

Practice Improvement
Since 2012, the American Board Specialties, due to a lack of formal bariatric surgery, and high-
of Obesity Medicine (www.abom fellowship training programs, cre- intensity weight loss counseling
.org) has offered certification in ates challenges for clinicians who is generally covered, as man-
obesity medicine. More than want to practice in the field. dated by the Patient Protection
600 physicians in the United and Affordable Care Act. How-
States take the examination Inconsistent and inadequate re- ever, Medicare Part D excludes
each year. However, the lack of imbursement for obesity thera- medications for weight loss,
recognition of obesity medicine pies creates additional chal- which has led most private health
by the American Board of Medical lenges. Most insurance plans plans not to cover pharmacother-
now have some coverage for apy for obesity.

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 In the Clinic Patient Information and Dietary Guidelines
www.eatright.org/search-results?keyword=obesity

Tool Kit
Dietary guidelines from the Academy of Nutrition and
Dietetics.
https://health.gov/dietaryguidelines/2015/guidelines
/executive-summary
2015-2020 Dietary Guidelines for Americans from the
U.S. Department of Agriculture.
Obesity www.uconnruddcenter.org/weight-bias-stigma
Weight bias and stigma information for patients and
providers from The Rudd Center.

IntheClinic
www.cdc.gov/obesity/resources/strategies-guidelines
.html
Nutrition, physical activity, and obesity prevention strategies
from the Centers for Disease Control and Prevention.

Clinical Guidelines and Other Information for

Health Professionals
www.amga.org/wcm/PI/Collabs/OCMC/ResourceGuide
/AHA.ACC.TOS_Guideline.pdf
2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the Ameri-
can College of Cardiology/American Heart Association
Task Force on Practice Guidelines and The Obesity
Society.
www.endocrine.org/guidelines-and-clinical-practice
/clinical-practice-guidelines/pharmacological
-management-of-obesity
Pharmacologic management of obesity guideline
resources from the Endocrine Society.
www.aace.com/files/publish-ahead-of-print-final-
version.pdf
2013 update of clinical practice guidelines for the periop-
erative nutritional, metabolic, and nonsurgical support
of the bariatric surgery patient from the American Asso-
ciation of Clinical Endocrinologists, The Obesity Soci-
ety, and the American Society for Metabolic and Bariat-
ric Surgery.

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 WHAT YOU SHOULD In the Clinic
Annals of Internal Medicine
KNOW ABOUT OBESITY
What Is Obesity?
Obesity is when you have more body fat than is
healthy. Too much body fat can cause serious
health problems, such as diabetes and arthritis.
Obesity can even shorten your life. Hormonal
changes occur in the body with any degree of
weight loss. These hormones make it hard to
lose weight and keep it off. Many factors play a
role in how much you weigh, including:
• The foods you eat
• How active you are
• Your family history
• Your sleep habits
• Taking certain medicines
• Other health problems
How Is It Diagnosed?
Your health care provider will ask you about your • Making sure to get more than 6 hours of sleep
health and weight history. This may include each night (ideally 8 hours).
questions about your eating habits, activity level,
and previous weight loss attempts. What Diet Is Best for Long-Term
Your provider will measure your weight and height in Weight Loss?
order to calculate your body mass index (BMI). In
general, if your BMI is between 25 and 29, you will Research shows that there is not much difference
be diagnosed as overweight; if it is greater than 30, in long-term weight loss among different eating
you will be diagnosed as having obesity. Your pro- plans. The most important thing is finding a plan
vider may also measure your waist. that is easy for you to stick with and makes you
You will have a physical examination. feel good about yourself. Many popular diets
Simple blood tests may be done. are similar in that they recommend lean pro-
teins, vegetables and fruits, and some healthy
How Is It Treated? fats (nuts, avocados) while limiting refined car-
bohydrates (sugar, most breads, white rice, and
Your health care provider will talk to you about
most snack foods). Alternative diets also include

Patient Information
how you can lose weight. They will review your meal-replacement diets and intermittent fasting.
medications to see whether any of them might
be causing weight gain. They will also rule out Will I Need Medicine or Surgery to
other causes of obesity that may be treatable,
such as a thyroid disorder. Lose Weight?
Even a small amount of weight loss (5%–10%) can im- If you are not able to lose enough weight through diet
prove your health and lower your risk for complica- and exercise alone, your health care provider may
tions, such as diabetes. Together, you and your pro- talk to you about medicine to help you lose weight.
vider will agree on a weight loss goal and a plan that There are several different kinds available. If you
is right for you. Some strategies include: have severe obesity and have other health problems
• Eating a reduced-calorie diet that includes because of it, surgery may be an option. It can lower
plenty of fruits and vegetables. the amount of food your body can take in and help
• Limiting red meats, processed foods (chips, you eat less.
cookies, sugary cereals), and sugar-sweetened Questions for My Doctor
beverages like soda and juice.
• Eating out less often. • How much weight should I lose?
• Slowly increasing physical activity. Start small, • How many calories should I eat to lose weight?
and work up to 150 minutes per week (about • How can I become more active?
30 minutes per day most days of the week). • Where can I find weight loss support?
Include muscle-strengthening activities at least • I can't seem to stop eating. What should I do?
2 days per week. • Are any of the medicines I take causing me to
• Finding a support network. There are many gain weight? Are there alternatives?
online and in-person weight loss groups, such • Should I consider taking medicine to help me
as Weight Watchers. There are also free lose weight?
smartphone apps for weight loss. • Should I consider weight loss surgery?

For More Information

MedlinePlus
https://medlineplus.gov/obesity.html
American College of Physicians
www.acponline.org/practice-resources/patient-education/online
-resources/obesity

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 Appendix Table 1. Pharmacotherapy for Treatment of Obesity
Medication Mechanism Dose Monthly Controlled Notes
Cost, $*
Phentermine Sympathomimetic 8–37.5 mg/d 10–20 FDA Schedule IV FDA-approved only for short-term use,
but appropriate for long-term use if
clinical criteria are met (see text)
Diethylpropion Sympathomimetic 25–75 mg/d 20–30 FDA Schedule IV Similar to phentermine
Benzphetamine Sympathomimetic 20–50 mg 3 35–45 FDA Schedule III Similar to phentermine
times daily
Phendimetrazine Sympathomimetic 17.5–35 mg 2 to 10–20 FDA Schedule III Similar to phentermine
3 times daily
(maximum 70
mg/d)
Phentermine–topiramate ER† Sympathomimetic 7.5/46 mg/d to 200 FDA Schedule IV Requires completion of safety training to
(phentermine); appetite 15/92 mg/d prescribe (www.qsymiarems.com);
reduction/dysgeusia most effective
(topiramate)
Lorcaserin† Agonist of serotonin 20 mg/d 280 FDA Schedule IV Lower efficacy; fewer adverse effects
5-HT2C
Bupropion–naltrexone† Inhibits neuronal uptake of 32/360 mg/d 270 Prescription Intermediate effectiveness and
norepinephrine and adverse effects
dopamine (bupropion);
inhibits negative
feedback loop on
bupropion (naltrexone)
Orlistat Inhibits intestinal lipase 60 mg 3 times OTC: 45–50 Prescription Only FDA-approved weight agent
daily (OTC) Prescription: available OTC; lower efficacy and
120 mg 3 times 600 fewer adverse effects
daily
(prescription)
Liraglutide Agonist of glucagon-like 3 mg/d 1200–1300 Prescription Injectable; used in lower dose for type
peptide-1 2 diabetes; high efficacy and more
adverse effects

ER = extended-release; FDA = U.S. Food and Drug Administration; OTC = over the counter.
*From www.goodrx.com.
†Manufacturer coupons may decrease the price of these agents.

Appendix Table 2. Nutritional Monitoring in Weight Loss Surgery Patients*

Nutrient Recommended Laboratory Testing Notes When to Monitor†
Supplementation
Iron 18–45 mg/d Ferritin; iron and total Deficiency most common in Baseline, 1–3 mo after surgery, then annually;
Ferrous sulfate, 200 iron binding menstruating women; may need more frequently if levels are low or
mg, or ferrous capacity parenteral supplementation symptoms of anemia develop
gluconate, 300
mg/d
Vitamin B12 Oral, 350–1000 mcg/d; B12 level Supplementation important because Before surgery, then annually; more frequently
sublingual, 500 (methylmalonic neurologic defects may not if levels are low or neurologic symptoms
mcg/d; nasal spray, acid if needed) resolve if due to deficiency develop
500 mcg/wk; or
intramuscular, 1000
mcg/mo
Vitamin D 3000 IU/d Vitamin D level; intact Supplement to ≥30 ng/mL before Before surgery, then annually; more frequently
parathyroid surgery if levels are low, bone density is low, or
hormone in symptoms of deficiency
selected patients
Folic acid 800 mg/d; special Erythrocyte folate Macrocytic anemia Before surgery, then annually; more frequently
dosing in pregnancy level if levels are low or symptoms of anemia
develop
Thiamine 50 mg/d; 100 mg B1 level Acute deficiency: Wernicke Before surgery, then as needed for specific
intravenously or encephalopathy early in symptoms/signs
intramuscularly in postoperative period in setting of
setting of severe marked vomiting
deficiency
Calcium‡ 500 mg/d (men); 500 Serum calcium; intact Consider dual-energy x-ray Before surgery, then annually; include with
mg twice daily parathyroid absorptiometry at 1–2 y after annual basic metabolic panel
(women) (calcium hormone in surgery
citrate preferred) selected patients
Zinc, copper, vitamin A, Multivitamin tablet; Routine testing not Consider testing in special situations As needed for specific symptoms/signs
vitamin E special dosing if needed (hair loss, taste problems,
deficiency develops neutropenia, impaired vision,
neurologic problems, impaired
wound healing)

*Supplementation after weight loss surgery is lifelong and is best done with specialized bariatric multivitamins that are formulated
for improved absorption. Most patients should have a basic metabolic panel and a complete blood count done annually. Patients
with prediabetes or diabetes should have hemoglobin A1c level monitored at least annually. Lipid testing in weight loss surgery
patients is similar to that for general primary care but may need to be more frequent in selected patients.
†From reference 55 and from Parrott J, Frank L, Rabena R, Craggs-Dino L, Isom KA, Greiman L. American Society for Metabolic
and Bariatric Surgery integrated health nutritional guidelines for the surgical weight loss patient 2016 update: micronutrients.
Surg Obes Relat Dis. 2017;13:727-741.
‡Not included in most specialized bariatric supplements; must be taken separately.

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