Obesity Treatment: Drugs, Surgical Options and Popular Diets

Question 1

Medications available for treatment of obesity (5)

Answer 1

• Phentermine
• Orlistat (Rx: Xenical, OTC: Alli)
• Lorcasarin (Belviq)
• Phentermine/topiramate (Qsymia)
• Naltrexone SR/Bupropion SR (Contrave)

Question 2

Phentermine: MOA

Answer 2

• Increases NE content in brain
• Chemically related to amphetamine
• Non-addictive stimulant

Question 3

Phentermine: side effects

Answer 3

• Hypertension
• Headache
• Nervousness
• Sleep disturbance
• No evidence of serious SE when used as monotherapy –> most widely prescribed
• FDA approved for 3-month use
• Not approved for long-term use (no one willing to fund long-term studies)

Question 4

Orlistat: MOA

Answer 4

• Pancreatic lipase inhibitor
• Inhibits fat absorption by 30%

Question 5

Orlistat: side effects

Answer 5

• GI side effects: oily stools, urgency, flatulence (spray farts?!)
• Need multivitamin to prevent fat soluble vitamin deficiency
• DDIs: coumadin and cyclosporin (decrease drug levels)
• Limited use: increased cost, limited weight loss, no insurance coverage

Question 6

Lorcasarin (Belviq): MOA

Answer 6

• Recently FDA approved
• Selective serotonin 2C receptor agonist
• 2C receptors found only in brain (not on heart, will not cause cardiac toxicity like old serotonin weight loss drugs)
• Produce 4-5% weight loss

Question 7

Lorcasarin (Belviq): side effects

Answer 7

• No evidence of cardiac toxicity in patients followed out to 2 years
• Question: will it have similar level of efficacy to phen/fen (12-15% weight loss) without the cardiac side effects? No data yet.
• Costs $220-250/month

Question 8

Phentermine/topiramate (Qsymia): MOA

Answer 8

• Phentermine: sympathomimetic, exact MOA unknown, stimulates CNS activity
• Topiramate: blocks voltage-dependent sodium channels, augments GABA activity, antagonizes glutamate receptrs, inhibits carbonic anhydrase
• Combo drug like beta blocker/vasodilator used to treat hypertension
• Substantially more weight loss than with other medications: 10-12% of baseline weight

Question 9

Phentermine/topiramate (Qysmia): side effects

Answer 9

• Concerns that topiramate has teratogenic potential
• Use needs to be carefully controlled in women of reproductive age
• Negative pregnancy test before starting medication, pregnancy test documented monthly
• Side effects:
  
  • Dry mouth
  • Paresthesias
  • Insomnia
  • Dizziness
  • Anxiety
  • Irritability
  • Disturbance in attention

Question 10

Naltrexone SR/Bupropion SR (Contrave): MOA

Answer 10

• Newest weight loss medication
• Naltrexone: opioid receptor antagonist
• Bupropion: Dopamine/NE reuptake inhibitor
• Average weight loss ~5% of baseline
  
  • More effective than phentermine, locasarin
  • Less effective than phentermine/topiramate
• Also used as smoking cessation aid and antidepressant

Question 11

Naltrexone SR/Bupropion SR (Contrave): side effects

Answer 11

• Black box warning: risk of increased suicidal ideation
• Serious but uncommon risks:
  
  • Suicidal ideation
  • Lowering seizure threshold
  • Increased pulse and blood pressure
  • Rarely: increased LFTs, closed angle glaucoma

Question 12

Drugs used for other problems that can contribute to weight gain

Answer 12

• Birth control pills, Depo-Provera (shot)
• Anti-diabetics: sulfonylureas, insulin, TZD
• Mood stabilizers, anti-psychotics
• Glucocorticoids (e.g. prednisone)

Question 13

How to minimize weight gain effects of other drugs

Answer 13

• Monitor weight/lifestyle changes
• Choose a different drug
• Lower dose
• Weigh risks and benefits of medication

Question 14

Alternate drugs with weight loss as side effect (2)

Answer 14

• Bupropion
  
  • Some evidence for slow weight loss
  • If on other anti-depressant, can talk to psychiatrist about a possible switch for weight loss benefit
• Topiramate
  
  • Anti-seizure with weight loss SE at higher doses
  • With big dose: 10-12% weight loss
• Neither approved on their own for weight loss

Question 15

Benefits of bariatric surgery

Answer 15

• Weight loss roughly
  
  • Gastric bypass: 30% (50-60% of excess weight), maintained for > 15 years
  • Laparoscopic banding: 20-25%, decreased risk
• Sleep apnea: improved in almost all
• Hypertension: improved in 50%
• GERD: improved in most
• Urinary incontinence: improved in most
• Cancer deaths: decreased by 50%
• Great at reducing diabetes-related death
• 83% won’t need to take diabetes medications anymore
• Great at reducing death from CVD

Question 16

Risks of bariatric surgery

Answer 16

• Bypass: death rate = 0.7% within 30 days, 2-3% within 2 years
• Lap band: death rate = 0.1%
• Failure of surgery to produce weight loss: 10-15%
• Pulmonary embolism
• Anastomotic leaks and sepsis
• Wound infections and dehiscence (wound breaks open along suture)
• Anastomotic stricture: dilatation or re-operate
• Thiamine deficiency: early vomiting, Wernicke-Korsakoff psychosis

Question 17

Late risks of bariatric surgery

Answer 17

• Diarrhea, vomiting: dietary indiscretion (sign of poor outcome)
• Vomiting without diarrhea: consider stricture
  
  • UGI vs. endoscopy –> may respond to dilation
• Anastomotic ulcer: Fe+ deficiency anemia or bleeding
• Depression: 20% may last 3-6 months
• Protein calorie malnutrition: more common with malabsorptive procedures
• Folate deficiency: one prenatal vitamin/day
• B12 deficiency: 30% complication rate 1-9 years post-op
• Fe2+ deficiency: increased in menstruating women

Question 18

Characteristics of good candidate for bariatric surgery

Answer 18

• BMI > 35 with comorbidities
• OR BMI > 40 without comorbidities
• Comorbidities: diabetes, sleep apnea, reflux > hypertension, degenerative joint disease
• Age 20-60, some teenagers are candidates
• Family history of comorbidities
• Other failed therapy
• No serious, active cardiac, pulmonary, or psychiatric disease

Question 19

Characteristics of good candidate for pharmacotherapy

Answer 19

• BMI > 27 with comorbidities
• OR BMI > 30 without comorbidities