Initial assessment involves a physical exam and patient interview to classify the

presence of overweight or obesity and any obesity-related comorbidities. The

preferred method to classify overweight or obesity is to measure the BMI.

Measurement of WC will also aid in determining risk of obesity comorbidities.

However, measurement of waist circumference in patients with BMI greater than 35

kg/m2

is not necessary because it will likely be elevated and will add no additional

risk information.

7,12 BMI, WC, and obesity-related comorbidities are used to

determine the need to initiate treatment. S.B.’s BMI is 32.2 (91 kg/[1.68 m]

2

), which

is in obesity class I. Her waist circumference is greater than 88 cm, indicating

abdominal obesity that puts her at additional risk for increased morbidity and

mortality. S.B. also has hypertension, sleep apnea, and osteoarthritis, which are

likely related to obesity and will need to be considered in her overall care plan.

During the patient interview, information should be obtained regarding the

patient’s eating habits and physical activity. It is important to establish baseline data

so that response to changes in diet and exercise is noted throughout treatment.

Successful weight loss involves a change in energy balance through reduced caloric

intake or increased energy expenditure. In S.B.’s case, it will be beneficial to

evaluate her current diet and physical activities to determine the most appropriate

lifestyle recommendations. It is also important to evaluate a patient’s “weight loss

readiness” or self-motivation before initiation of therapy. A patient’s motivation to

lose weight is a significant predictor of success or failure in the weight management

program. S.B.’s desire and willingness to make significant lifestyle changes in order

to achieve this should be evaluated.

Patients should also be screened for medical conditions or medications that can

increase the risk for obesity, and these underlying factors should be corrected before

recommending treatment. S.B.’s past medical history does not indicate any overt

medical causes of obesity, but it would be appropriate to rule out whether she is

overeating due to her depression and to check thyroid function to rule out

hypothyroidism. Even though causality between obesity and thyroid dysfunction has

yet to be firmly established, hypothyroidism is a common condition in women and

may be associated with weight gain or inability to lose weight. S.B. is currently

taking paroxetine for depression which has been associated with weight gain.

6,58

S.B.’s prescriber may want to consider switching to fluoxetine which is the SSRI that

is associated with the least amount of weight gain or bupropion which is associated

with weight loss (Table 36-3).

6,57,58

p. 760

p. 761

Course and Prognosis

CASE 36-1, QUESTION 2: S.B. states that she has struggled with her weight her whole life. She has

progressively gained approximately 2 kg/year since her 20s.What is the typical course and prognosis of obesity?

Obesity is a chronic disease that often begins in childhood or adolescence and can

be characterized by a slow and steady increase in body weight during adult life. Most

patients with obesity battle with weight loss and regain throughout their entire lives.

The biologic response to weight loss favors regain with increased ghrelin and

reductions in GLP-1, CCK, leptin, and PYY resulting in increased hunger.

6,59

Maintaining weight loss is key to long-term management of obesity. S.B. should be

assured that her struggle is common and that she will need to commit to long-term

lifestyle changes to manage her obesity.

Medical Complications

CASE 36-1, QUESTION 3: S.B. understands that she already has hypertension, sleep apnea, and

osteoarthritis, which are comorbidities that are related to her obesity and increase her risk of morbidity and

mortality. She is also at risk for experiencing additional obesity-associated medical comorbidities if she does not

lose or continues to gain weight. What are the other common medical conditions associated with obesity? What

impact will weight loss have on comorbid conditions?

Obesity is associated with an increased risk of morbidity and mortality. Some

obesity-associated diseases that are generally not life-threatening include

dermatologic complications, osteoarthritis, reproductive complications, gallstones

and their complications, and stress incontinence. Other obesity-related conditions

have a tremendous impact on physiologic functioning and medical illnesses. Obesity

is linked to many significant health conditions such as type 2 diabetes mellitus,

respiratory conditions, gallbladder disease, cancers, osteoarthritis, cardiac disease

(hypertension, stroke, congestive heart failure, and coronary heart disease),

dyslipidemia and dermatologic problems (intertrigo and stretching of skin), and

gynecologic and obstetric complications (Table 36-2).

60,61 Weight loss helps to

control diseases associated with obesity and may even help prevent development of

these diseases.

Health benefits have been shown with modest sustained weight loss. Weight loss

of 2% to 5% is associated with reducing hemoglobin A1C by 0.2% to 0.3% in

patients with type 2 with overweight or obesity and weight loss of 5% to 10% is

associated with up to 1% reduction in A1C.

7 Five percent weight loss is associated

with reducing systolic blood pressure by 3 mm Hg and diastolic blood pressure by 2

mm Hg. Weight loss of 5 to 8 kg has been shown to reduce low-density lipoprotein

cholesterol (LDL-C) by approximately 5 mg/dLand increase high-density lipoprotein

cholesterol (HDL) by 2 to 3 mg/dL and triglycerides are lowered by 15 mg/dL with

just 3 kg weight loss.

7

In S.B.’s case, weight loss could help her decrease or

eliminate medications needed to control her hypertension, alleviate pain associated

with osteoarthritis, decrease symptoms of sleep apnea, and reduce her BMI and WC,

therefore improving her morbidity and mortality risk. In the meantime, her

hypertension is currently uncontrolled and should be aggressively managed per the

current guidelines.

MANAGEMENT AND TREATMENT

Obesity is a chronic disease that requires lifelong effort for successful treatment.

6,7

Treatment may involve a multidisciplinary approach including the expertise of a

general practitioner, dietician or nutrition specialist, pharmacist, psychiatrist, or

surgeon depending on the specific needs of the individual. The general goals of

weight loss and management are to prevent weight gain, reduce body weight, and

maintain weight loss over a long period.

Medical Management

CASE 36-1, QUESTION 4: S.B. reports that she has never received dietary counseling from a medical

professional and has always dieted on her own by restricting fat intake. S.B. expresses a desire for weight loss

therapy. What are appropriate goals for S.B.’s weight loss? What should the initial treatment plan include?

Weight loss is recommended for patients who have obesity (BMI ≥30) or those

who are overweight, who have obesity-related comorbidities or increased waist

circumference.

7 An appropriate initial goal for weight loss is 5% to 10% of baseline

weight within 6 months.

7 Setting appropriate achievable weight loss goals is

important to success; unrealistic expectations for more dramatic weight loss may lead

to disappointment and ultimately cause patients to stop any efforts toward weight

loss. An appropriate goal for S.B. is 4.55 to 9.1 kg within 6 months. Treatment

options to facilitate weight loss include lifestyle interventions and anti-obesity

medications. S.B. questioned her physician about weight loss medications, but she

has never made an effort to lose weight through a structured weight loss program.

The initial treatment plan must always include a reduced calorie diet, increased

physical activity, and behavioral modifications. These measures must be attempted

and maintained for at least 6 months before considering pharmacotherapy.

7

Nonpharmacologic Therapy

CASE 36-1, QUESTION 5: S.B. reports that she has never received dietary counseling from a medical

professional and has always dieted on her own by restricting fat intake. Although she has not attempted to lose

weight recently, S.B. expresses desire to try a program for weight loss and start an exercise regimen. What

types of nonpharmacologic therapies are available for weight reduction and relapse prevention?

Comprehensive lifestyle interventions including a calorie- restricted diet,

increased physical activity, and behavioral modifications are the foundation of

weight loss therapy.

DIET

Diets for weight loss promote caloric restriction. Caloric recommendations for

women seeking to lose weight are 1,200 to 1,500 kcal/day and 1,500 to 1,800

kcal/day for men; alternatively, a deficit of 500 to 750 kcal/day is associated with

weight loss.

7 Because of the high demand by consumers, there are numerous types of

weight loss programs, diets, and products that may or may not be effective for each

individual patient. A variety of dietary interventions have been proven successful in

weight loss including low-fat diets, higher protein diets, low carbohydrate diets,

restricted carbohydrate diets, meal replacement and liquid diets, dietary pattern such

as the Mediterranean diet.

7 Research suggests clinically meaningful weight loss is

achieved through a reduced calorie diet regardless of the composition of dietary

macronutrients.

62

p. 761

p. 762

EXERCISE

Increased physical activity will contribute to the negative energy balance that is

required for weight loss. Increased physical activity is essential in preventing weight

gain. Overweight children and adults should have at least 30 minutes of moderateintensity physical exercise daily (with a gradual increment of increasing exercise by

several minutes each day up to 30 minutes/day). It has been shown that moderate

exercise (e.g., 4 kcal/g/week) can improve physiologic variables.

63,64

BEHAVIOR THERAPY

The most effective lifestyle intervention includes frequent counseling (>14) group or

individual sessions per month with a trained interventionist (registered dietician,

nutrition counselor, psychologist, exercise specialist, health counselor, or other

trained professional).

Individuals who want to lose weight frequently seek out popular structured

programs (e.g., Jenny Craig, Weight Watchers) and these programs have also been

proven successful in producing weight loss. Clinical trials that compared dietary

interventions conclude that the most effective diet is one that the patient is able to

comply with long term.

62,65

Overall, a combination of a reduced-calorie diet and increased physical activity

with support of a trained interventionist is the most effective for reducing and

maintaining weight loss. Given that obesity is a chronic condition, S.B. must select a

comprehensive lifestyle intervention that is most appealing to her so that she will be

able to comply with it long term.

Pharmacologic Therapy

CASE 36-1, QUESTION 6: S.B. returns to her physician for follow-up 6 months later. She has managed to

lose 7 kg and is at a weight of 84 kg. Based on her BMI of 29.8 kg/m

2

, her weight is classified as overweight.

Her depression, osteoarthritis, sleep apnea, and hypertension have improved (current blood pressure is 142/88

mm Hg). Her current medication profile includes bupropion, hydrochlorothiazide, metoprolol, and acetaminophen

as needed. Although she has achieved her goal with 7.7% weight loss and is now considered overweight and

not obese, S.B. is disappointed that her weight loss has plateaued. She still wants to lose additional weight. She

again asks the physician about short-term anti-obesity medications that can help accelerate her weight loss.

Would a short-term agent be appropriate for S.B.? What are the mechanisms of action, efficacy, and potential

adverse effects of the short-term anti-obesity medications?

As previously stated, a comprehensive lifestyle intervention is the foundation of

weight loss management. Although weight loss is possible for most patients, it is not

sustainable and regain is common.

66 Obesity is a chronic, lifelong illness that may

require long-term medication therapy. Medication should be considered only for

patients with a BMI ≥30 kg/m2 without risk factors or BMI ≥27 kg/m2 with an

obesity-related comorbid medical condition such as hypertension, dyslipidemia, type

2 diabetes, and obstructive sleep apnea (Table 36-2).

6 Medications should not be

considered a replacement for diet, behavioral modification, and exercise, but rather

as adjunctive therapy. Currently, marketed anti-obesity drugs cause weight loss by

suppressing the appetite or decreasing the absorption of fat.

67

S.B. is a candidate for pharmacotherapy even though her BMI is currently

considered overweight at 29.8 kg/m2

, her obesity-related comorbidities of

hypertension and sleep apnea qualify her for medication therapy. The most

appropriate medication for S.B. must be based on her current medication profile and

her comorbid health conditions.

SHORT-TERM THERAPY

Obesity is a chronic disease state; therefore, the clinical usefulness of short-term

therapy is unlikely to have a meaningful impact. The FDA has approved several

weight loss drugs for short-term use defined as <12 weeks, and these include

phentermine, diethylpropion, phendimetrazine, and benzphetamine. All are

sympathomimetic agents that function as appetite suppressants.

68,69 Of these drugs,

phentermine is the most commonly prescribed and is frequently prescribed, off-label,

for long-term therapy.

68

Phentermine is approved for adjunctive therapy in patients older than 16 years of

age, at a dosage of 18.75 to 37.5 mg taken 2 hours after breakfast. Dosing may also

be divided into two 18.75 mg doses.

70 The most common adverse effects associated

with phentermine therapy are insomnia and dry mouth.

68 Phentermine has also been

associated with cardiovascular effects, including case reports of pulmonary

hypertension, and as such is contraindicated in patients with cardiovascular disease

and hypertension.

71,72 Phentermine also has abuse potential and is considered a

controlled substance (schedule IV drug), which further limits its use as a weight loss

agent.

69

Diethylpropion, phendimetrazine, and benzphetamine exhibit appetite suppressive

actions similar to phentermine, but are less widely prescribed.

68 They also share

adverse effects and contraindications similar to phentermine.

68,69 The abuse potential

with these drugs is high, with diethylpropion classified as a schedule IV drug and

benzphetamine and phendimetrazine classified as schedule III drugs.

69 Based on their

approval for short-term use, adverse effects and abuse potential, none of these agents

should be recommended for weight loss therapy.

S.B.’s physician should not prescribe short-term weight loss medications to S.B.

Short-term agents for obesity may increase S.B.’s blood pressure. Also short-term

agents will not provide the necessary long-term treatment for S.B.’s chronic

condition.

CASE 36-1, QUESTION 7: S.B. realizes that her obesity is a chronic condition and inquires about long-term

medications for weight loss. What agents are available for the long-term treatment of obesity? (see Table 36-4)

LONG-TERM THERAPY

Orlistat (Xenical, Alli)

Orlistat is FDA-approved for long-term obesity management as an adjunct to lifestyle

modification.

73 Orlistat 120 mg was originally marketed under the trade name

Xenical. Then, in February 2007, the FDA approved the OTC marketing of orlistat,

under the trade name Alli, at a 60 mg dose.

74 Orlistat works to reduce dietary fat

absorption by inhibiting GI (stomach and pancreatic) lipase activity.

75,76 Gastric and

pancreatic lipase are enzymes that play a pivotal role in the digestion of dietary fat

(triglycerides). By inhibiting these lipase enzymes, orlistat prevents the hydrolysis

and absorption of triglycerides.

73,77 This results in the excretion of approximately

30% of ingested fat in the feces.

68 Orlistat does not exert appetite suppressant effects,

has no CNS effects, and has no systemic absorption.

76 The therapeutic activity of

orlistat takes place in the stomach and small intestine and effects are seen as soon as

24 to 48 hours after dosing.

In a meta-analysis, orlistat was shown to produce average weight loss of 2.9 kg or

2.9% greater than placebo.

78 Additionally, a 4-year prospective, double-blind,

randomized study, XENDOS, found that orlistat plus lifestyle changes was associated

with a 37.3% risk reduction of type 2 diabetes in greater than 3,300 high-risk obese

patients.

79 Use of orlistat has also been associated with improvements in blood

pressure, as well as improvement in metabolic parameters such as fasting serum lipid

profiles and C-reactive protein.

78,80,81

p. 762

p. 763

Table 36-4

Medications for the Treatment of Obesity

Generic Name Trade Name Dosing

Orlistat Xenical 120 mg PO TID

Alli 60 mg PO TID

Phentermine/topiramate Qsymia 3.75/23 mg PO QAM × 14 days; then 7.5/46 mg QAM

for 12 weeks then evaluate weight loss, if less than 3%,

dose may be titrated to 11.25/69 mg QAM × 14 days

then 15/92 mg QAM

Lorcaserin Belviq 10 mg PO BID

Naltrexone/bupropion Contrave 8/90 mg PO QAM × 1 week then 8/90 mg BID ×1

week then 16/180 mg QAM and 8/90 mg QPM then

16/180 mg BID

Liraglutide Saxenda 0.6 mg SC daily × 1 week increase dose by 0.6 mg

weekly until therapeutic dose of 3 mg daily

Phentermine hydrochloride

a Adipex-P TID; 30–37.5 mg QAM

aNot recommended for routine or long-term use.

BID, 2 times a day; OTC, over the counter; PO, by mouth; QAM, every morning; QPM, every evening; SC,

subcutaneously; TID, 3 times a day.

The most common adverse effects associated with orlistat include GI problems

(loose stools, oily spotting, flatus with discharge, fecal urgency, fatty or oily stools,

increased defecation, fecal incontinence, bloating, and cramping).

82 The most

common non-GI adverse effect was headache (6%). Side effects usually develop

early in treatment and persist for 1 to 4 weeks, but occasionally last longer than 6

months. Because GI adverse effects are worse with a high-fat diet, orlistat may

enhance dietary compliance with a low-fat diet. Side effects that continue to be

problematic have been associated with nonadherence to orlistat therapy and therefore

variability in patient outcomes. Rare cases of oxalate-induced acute kidney injury

and liver injury have been reported with use of orlistat.

83,84

Orlistat may reduce the absorption of fat-soluble vitamins (A, D, E, and K) and

patients should take a multivitamin supplement that contains these vitamins.

82 The

supplement should be taken once a day at least 2 hours before or after the

administration of orlistat, such as at bedtime. Reduced absorption of vitamin K may

potentiate the bleeding effects of warfarin. Reduced absorption of vitamin D may

lead to metabolic bone disease; supplementation with higher doses of vitamin D may

be required.

85 Orlistat may also reduce the absorption of lipophilic drugs including

amiodarone, cyclosporine, lamotrigine, and valproic acid.

76,86 Orlistat is

contraindicated in pregnancy and in patients with chronic malabsorption syndrome,

or cholestasis.

73

Phentermine/Topiramate ER (Qsymia)

Phentermine/topiramate ER is a combination drug that has been approved by the FDA

for long-term obesity management as an adjunct to lifestyle modification.

87