Lipari Obesity

What medications can contribute to weight gain?

Increases appetite:

Anticonvulsants/mood stabilizers, antidepressants, antipsychotics,

antidiabetics, antihistamines (H1 blockade increases appetite), corticosteroids (hormonal appetite), contraceptives (hormonal appetite)

Decreases metabolism:

nonselective beta-blockers

Which anticonvulsants/mood stabilizers contribute to weight gain?

All increase appetite in the brain:

Carbamazepine, gabapentin, lithium, pregabalin, and valproic acid.

Which antidiabetics contribute to weight gain?

All increase appetite due to hypoglycemia:

Insulin, meglitinides, sulfonylureas, and thiazolidinediones.

Which antidepressants contribute to weight gain?

All increase appetite in the brain:

Monoamine oxidase inhibitors, presynaptic α antagonist (mirtazapine), and serotonin and norepinephrine reuptake inhibitors (duloxetine).

Where do we take hunger and satiety mechanisms from?

Our hypothalamic hunger and satiety mechanisms take input from:

1. fat tissue via leptin

2. the gut via ghrelin,

3. GLP-1, and other hormones

4. by direct sensing of prevailing glucose

In what situations is BMI overestimated?

Extreme muscularity, short stature, and muscle loss in older patients.

What waist circumference values indicate increased obesity risk?

Women: >35 inches; men: >40 inches

What else is used in clinical presentation and diagnosis of obesity besides BMI and waist circumference?

Fat percentage, comorbidities, and readiness to lose weight.

What are the percentile ranges for obesity in children?

Underweight: <5th percentile

Normal/Healthy Weight: 5th-84th percentile

Overweight: 85th-94th percentile

Obese: ≥95th percentile

What are the adult BMI classifications?

Underweight: <18.5

Normal weight: 18.5-24.9

Overweight: 25.0-29.9

Obese class I: 30.0-34.9

Obese class II: 35.0-39.9

Obese class III: ≥40

What are the exclusions for self-treatment of obesity?

Severe obesity (BMI>40)

Pregnancy/breastfeeding

<18 years of age or >65 years of age

Untreated secondary cause of obesity (disease)

Eating disorder

What cardiovascular complications are associated with obesity?

Atrial fibrillation, congestive heart failure, and HTN.

What dermatologic complications are associated with obesity?

Cellulitis, psoriasis, and striae distensae (stretch marks).

What endocrine/reproductive complications are associated with obesity?

Infertility, polycystic ovarian syndrome, and amenorrhea.

What gastrointestinal complications are associated with obesity?

GERD, hepatic cirrhosis, and hernias.

What genitourinary complications are associated with obesity?

CKD/ESRD and urinary stress incontinence.

(ESRD= end stage renal disease)

What metabolic complications are associated with obesity?

Diabetes mellitus, hyperlipidemia, and metabolic syndrome.

What musculoskeletal complications are associated with obesity?

Fibromyalgia, immobility, and degenerative joint disease.

What is the initial percent weight-loss goal?

5-10% body weight loss from baseline over about 6 months.

What weight loss percent leads to reduction in cardiovascular disease?

3-5% body weight loss.

What BMI ranges indicate the need for lifestyle modifications?

Diet, exercise, behavior therapy are suggested for

BMI 25-29.9 with comorbidities

or

BMI 30+ without comorbidities

What BMI ranges indicate the need for pharmacotherapy?

BMI 27-29.9 with comorbidities

or

BMI 30+ without comorbidities

What BMI ranges indicate the need for surgery?

BMI 35-39.9 with comorbidities

or

BMI 40+ with diabetes or metabolic disease

What did the POUNDS LOST study show?

Weight loss was similar across popular diets. Reducing energy intake is more important than which specific diet you choose.

Which diets are recommended by the dietary advisory committee?

The US Healthy Eating Pattern (DASH: Dietary Approaches to Stop Hypertension)

Mediterranean Eating Pattern

What is the recommended calorie deficit for diet therapy?

Decrease 500-750 kcal/day to achieve 1-2 lb./week weight loss

What is the low calorie diet intake for most women and men?

Most women: 1,000-1,200 kcal/day

Most men: 1,200-1,600 kcal/day

What is the very low-calorie diet recommendation?

≤800 kcal/day

Not recommended!! Nutritionally inadequate and not more effective than low calorie diet long term

How is total energy expenditure calculated?

TEE = BEE * PAL

(Total Daily Energy Expenditure = Basal Energy Expenditure * Physical Activity Level)

What are the physical activity level categories, activity factors, and definitions?

Sedentary: 1.2, little or no exercise and desk job

Lightly active: 1.375, light exercise or sports 1-3 days a week

Moderately active: 1.55, moderate exercise or sports 3-5 days a week

Very active: 1.725, hard exercise or sports 6-7 days a week

Extremely active: 1.9, hard daily exercise or sports and physical job

What is the exercise goal for obesity management?

Aerobic activity for >150 minutes/week for 3-5 days per week.

Resistance exercise involving major muscle groups 2-3 times per week.

What are the indications for pharmacotherapy in obesity?

Failure to lose 1 lb/week after 6 months of combined lifestyle therapy

Comorbidities: hypertension, dyslipidemia, coronary heart disease, type 2 diabetes, and sleep apnea

What are the short-term obesity agents, doses, and controlled substance schedules?

Phentermine (Adipex-P), 15-37.5 mg daily, Schedule IV

Diethylpropion (Tenuate), 25 mg tid or 75 mg ER daily, Schedule IV

Phendimetrazine, 17.5-35 mg 2-3 times daily or 105 mg ER daily, Schedule III

What is the MOA for short-term obesity agents?

Inhibits NE reuptake or stimulates NE release

What are the side effects of phentermine?

Increased BP, HR

Palpitations

Constipation/diarrhea

Dry mouth

Headache

Insomnia

Euphoria

Urticaria

Impotence

Pretty much everything that is caused by the symp. nervous system

What are the contraindications of phentermine?

Pulmonary HTN

Moderate to severe HTN

Atherosclerosis

Cardiovascular disease

Hyperthyroidism

Glaucoma

MAO-Is

Agitated states

History of drug abuse

Pretty much everything that is worsened by the symp. nervous system

What is the MOA and contraindication profile of orlistat?

Inhibits lipases, preventing the breakdown of triglycerides into free fatty acids.

Contraindicated in patients with malabsorption and cholestasis.

What is the orlistat: Alli (OTC) dosage and adverse effects?

60 mg TID with fatty meals, short-term

Adverse effects: flatulence w/ discharge, fecal urgency/incontinence/oily stools, abdominal pain, malabsorption of vitamins ADEK

What is the orlistat: Xenical (Rx) dosage and adverse effects?

Weight loss?

120 mg TID with fatty meals, long-term

Adverse effects: rare cases of severe liver injury

Weight loss: -2.36 kg

What are the interactions of orlistat?

May increase effects of warfarin due to decreasing dietary vitamin K absorption.

May decrease effects of lipophilic drugs: amiodarone, cyclosporine, antiepileptics (lamotrigine, valproic acid, gabapentin), levothyroxine, vitamins (ADEK), beta-carotene.

What is the MOA of phentermine/topiramate ER (Qsymia)?

Phentermine MOA: noradrenergic appetite suppressant

Topiramate MOA: antiepileptic

What is the dose of phentermine/topiramate ER (Qsymia)?

Weight loss?

3.75/23 mg for 14 days.

Increase dose to 7.5/46 mg once daily for 12 weeks.

Further dose titrations based on % body weight loss, long-term.

Weight loss: -8.1 kg

What are the adverse effects of phentermine/topiramate ER (Qsymia)?

Common: dry mouth, tingling, constipation, altered taste, insomnia

Serious: depression, cognitive disorders, tachycardia, decreased bicarbonate

(Phentermine → stimulant effects, Topiramate → neurologic & metabolic effects)

What is the MOA of naltrexone ER/bupropion ER (Contrave)?

MOA not well known for weight loss.

May result from action in hypothalamus (appetite regulatory center) and dopamine circuit (reward system).

What is the dose of naltrexone ER/bupropion ER (Contrave)?

Weight loss?

360/16 or 360/32 mg daily in 2 divided doses, 4-week titration.

If 5% of baseline body weight not lost after 12 weeks, discontinue therapy.

Weight loss: -4.53 kg

What are the adverse effects of naltrexone ER/bupropion ER (Contrave)?

Common: nausea, vomiting, constipation, headache, dizziness, insomnia, dry mouth.

Serious: seizure, palpitations, cholecystitis.

(Naltrexone → GI upset, Bupropion → stimulant effects)

What is the MOA of liraglutide (Saxenda), semaglutide (Wegovy), and orforlipron (Foundayo)?

Glucagon-like peptide (GLP-1) receptor agonist: slows gastric emptying and decreases food intake.

What is the dose of liraglutide (Saxenda)?

Weight loss?

0.6 mg subq once daily x 1 week.

Increase by 0.6 mg daily at weekly intervals to a target dose of 3 mg subQ daily, long term.

Evaluate change in body weight 16 weeks after initiation of therapy.

Discontinue if at least 4% of baseline body weight loss has not been achieved.

Weight loss: -5.01 kg

What are adverse effects of GLP-1s?

Abdominal pain, constipation, decreased appetite, diarrhea, dizziness, dyspepsia (indigestion), fatigue, headache, hypoglycemia, increased lipase, nausea, vomiting.

Pretty much all GI issues lol

What are contraindications for GLP-1s?

Personal or family history of medullary thyroid cancer.

Multiple endocrine neoplasia type 2 (MEN2).

(because GLP-1's may cause thyroid hyperplasia)

What is the dose of subQ semaglutide (Wegovy)?

Weight loss?

Week 1-4: 0.25 mg once weekly

Week 5-8: 0.5 mg once weekly

Week 9-12: 1 mg once weekly

Week 13-16: 1.7 mg once weekly

≥Week 17: 2.4 mg once weekly

Discontinue therapy if <5% baseline body weight not achieved within 3 months.

Weight loss: -9.2 kg

What are additional adverse effects of semaglutide (Wegovy)?

(not seen with Saxenda)

Abdominal distension, eructation (burping), flatulence, gastroenteritis, GERD.

Basically more gas

What is the dose of oral semaglutide (Wegovy)?

Day 1-30: 1.5 mg once daily

Day 31-60: 4 mg once daily

Day 61-90: 9 mg once daily

Day 91+ (maintenance): 25 mg once daily

Take in the morning on an empty stomach, ≥30 minutes before consuming food, beverages, or other medications.

Discontinue therapy if <5% baseline body weight not achieved within 3 months.

What is the dose of orforlipron (Foundayo)?

Weight loss?

Day 1-30: 0.8 mg once daily

Day 31-60: 2.5 mg once daily

Day 61-90: 5.5 mg once daily

≥Day 91: increase to next dosage level (9 mg, 14.5 mg, or 17.2 mg once daily) after 30 days on current dose.

No fasting requirement (which differs from oral semaglutide).

Discontinue therapy if <5% baseline body weight not achieved within 3 months.

Weight loss: -12.27 kg

What is the MOA of tirzepatide (Zepbound)?

GLP-1 and glucose-dependent insulinotropic polypeptide (GIP): slows gastric emptying and decreases food intake.

What is the dose of tirzepatide (Zepbound)?

Weight loss?

Week 1-4: 2.5 mg once weekly

Week 5-8: 5 mg once weekly

May further increase dose in 2.5 mg/week increments every 4 weeks, if needed (maximum weekly dose: 15 mg/week)

Discontinue therapy if <5% baseline body weight not achieved within 3 months.

Weight loss: -16.72 kg

What are the adverse effects of tirzepatide (Zepbound)?

Abdominal pain, alopecia (from weight loss), constipation, diarrhea, dyspepsia, eructation, fatigue, GERD, hypersensitivity, injection site reactions, nausea, vomiting.

Pretty much all GI issues

What are the 2022 AGA recommendations with strong recommendation and moderate certainty?

Pharmacologic therapy + Lifestyle Intervention (LSI).

What are the 2022 AGA recommendations with conditional recommendation and moderate certainty?

Semaglutide 2.4 mg + LSI

Liraglutide 3 mg + LSI

Naltrexone/bupropion ER + LSI

Phentermine/topiramate ER + LSI

(more specific drugs = conditional recommendation instead of strong recommendation)

What are the 2022 AGA recommendations with conditional recommendation and low certainty?

Phentermine (short-term) + LSI

Diethylpropion (short-term) + LSI

(because they're seen in old studies, short-term use)

T/f: The AGA recommends against the use of Orlistat

True, but a patient can still use it if they don't mind the side effects and lesser weight loss

What is the staged treatment approach for children's weight management?

Start with #1 and move to more intensive treatment if needed.

1. Prevention (promote healthy habits to prevent weight gain)

2. Structured (planned meals and snacks)

3. Comprehensive multidisciplinary (involving a physician, dietitian, psychologist)

4. Tertiary care (weight loss meds)

How long is short-term pharmacotherapy?

These drugs should only be continued if patient has satisfactory weight loss within first ____ weeks

12 weeks total

4 weeks

T/f: Tirzepatide and orforglipron were approved by the FDA at the time of

publication of the 2022 AGA recommendations

False.

But once these drugs are approved, they will likely be preferred over older drugs, possibly over semaglutide.