II. Indications

  1. Follow indications strictly!!
  2. Morbid Obesity (BMI>30)
  3. Moderate Obesity (BMI 27) with comorbidity

III. Approach

  1. Employ all other weight loss strategies concurrently
    1. See Obesity Management
    2. See Exercise in Obesity
    3. Avoid Medications Associated with Weight Gain
  2. First-line agents
    1. Orlistat
      1. Preferred among the Obesity Medications as first -line
  3. Reevaluate efficacy, compliance and adverse effects on a schedule
    1. Stop weight loss medications if patient fails to lose 5% body weight after 12 weeks at maximal dose
    2. Document BMI and treatment plan at a minimum of every 6 months
  4. Most Obesity Medications are expensive
    1. Most agents are $200 per month
    2. Phentermine and Orlistat are least expensive at $30 and $45/month respectively
    3. Saxenda is most expensive at >$1000/month

IV. Management: Medications (most are DEA Controlled agents)

  1. FDA Schedule 4 Medications
    1. Phentermine (Fastin, Adipex-P, Lonamin)
    2. Diethylpropion (Tenuate)
    3. Lorcaserin (Belviq)
  2. FDA Schedule 3 Medications
    1. Benzphetamine (Didrex)
    2. Phendimetrazine (Bontril)
  3. Non-FDA-Scheduled medications
    1. Orlistat (Xenical)
    2. Liraglutide (Saxenda)

V. Management: Combination Protocols

  1. Phentermine and Prozac
    1. Phentermine 30 mg orally daily
    2. Prozac 20 mg orally daily
  2. Phentermine and Topiramate (Qsymia, previously Qnexa)
    1. See Qysmia
  3. Bupropion and Naltrexone
    1. Contrave (90 mg Bupropion with 8 mg Naltrexone) tablet orally daily, gradually advanced to 2 tablets twice daily

VI. Management: Dietary Supplements

  1. See Dietary Supplements in Obesity
  2. Patients on Orlistat should take a daily MVI with the fat soluble Vitamins (Vitamin A, Vitamin D, Vitamin E and Vitamin K)

VII. Preparations: GLP-1 Analogs

  1. Semaglutide Injection (Ozempic, Wegovy up to 2.4 mg/week)
    1. Mean weight loss 13% body weight (at least 5% in most patients) and sustained >1 year while on Semaglutide
    2. Incretin Mimetic (GLP-1 Analog) used in Type II Diabetes Mellitus
      1. Titrated to 2.4 mg (instead of the 1 mg used in Type II Diabetes Mellitus alone)
    3. Start at 0.25 mg injected weekly, and slowly titrate monthly (0.5, 1, 1.7, 2.4 mg) over 16 weeks to maximum of 2.4 mg weekly
      1. Expect 10-12% weight loss at one year (twice the weight loss of Saxenda)
      2. Stop medication if inadequate weight loss (<5% at 12 weeks of 2.5 mg/week)
    4. Target dose 2.4 mg/week costs $1400/month in 2021
    5. Increased risk of Retinopathy complications (esp. if pre-existing Retinopathy)
    6. Adverse effects include increased Heart Rate (10-20 bpm in 40% of patients) and gastrointestinal symptoms
    7. Bald (2023) Am Fam Physician 107(1): 90-1 [PubMed]
  2. Tirzeptatide (Mounjaro)
    1. Single Agent GLP-1 Agonist and GIP Agonist (Twincretin)
    2. Weight loss in Diabetes Mellitus patients may approach 25 pound loss in 10 months
    3. Weight loss in patients without Diabetes was 15-21% of total body weight over a 72 week period
      1. Dose 5 mg/week reduced weight 15%, 10 mg/week reduced weight 19.5%, 15 mg/week reduced weight 20.9%
      2. Jastreboff (2022) N Engl J Med 387(3): 205-16 [PubMed]
    4. Same adverse effects and risks as with GLP-1 Agonists
    5. Also delays gastric emptying and may render Oral Contraceptives less effective
    6. No available data in 2022 on cardiovascular benefit (unlike some other GLP-1 Agonists)
    7. Cost in 2022: $1000 per month
    8. (2022) Presc Lett 29(7): 38-9

VIII. Preparations: General

  1. Qsymia (Phentermine and Topiramate)
    1. Results in 19-20 pound weight loss more than Placebo at 1 year
    2. May cause decreased cognition, Paresthesias, Tachycardia, Ureteral Stones (intolerable in 8%)
    3. Must be tapered gradually (due to risk of Seizure)
    4. Significant Teratogenicity risk (requires Informed Consent, reliable Contraception and monitoring with UPT)
  2. Saxenda Injection (Liraglutide up to 3 mg/day)
    1. Incretin Mimetic (GLP-1 Analog) used in Type II Diabetes Mellitus
      1. Titrated to 3 mg (instead of the 1.8 mg used in Type II Diabetes Mellitus alone)
    2. Results in 10-12 pound weight loss more than Placebo in one year
    3. May cause Nausea and rare Hypoglycemia (intolerable in 5%)
    4. Most expensive Obesity Medication (>$1000/month)
  3. Contrave (Bupropion and Naltrexone)
    1. Results in 9 to 10.8 lb (up to 4.9 kg) weight loss more than Placebo in one year
    2. May cause Nausea (intolerable in 12%)
    3. Contraindicated with concurrent Opioids, or Seizure Disorder, Uncontrolled Hypertension
    4. Suicidality risk (FDA black box warning)
  4. Lorcaserin (Belviq or Belviq XR)
    1. Results in 7-8 pound weight loss more than Placebo in one year
    2. May cause Dizziness, Fatigue (intolerable in 2%)
    3. Risk of Serotonin Syndrome when combined with other serotinergic agents (e.g. SSRI)
    4. Theoretical risk of valvulopathy (similar to Fenfluramine), but short-term studies demonstrated safety
  5. Orlistat (Xenical, Alli)
    1. Typically recommended as a first-line agent among the Obesity Medications
    2. Results in 7 pound weight loss more than Placebo in one year
    3. May cause Nausea, Diarrhea, fecal urgency (intolerable in 4%)
    4. Contraindicated in cholestasis, comorbidity causing malabsorption
    5. One of the least expensive of the Obesity Medications ($45/month)
    6. Package insert recommends taking MVI with fat soluble Vitamins (Vitamins A, D, E and K)
  6. Plenity (cellulose hydrogel)
    1. Cellulose hydrogel taken with water before meals, expands in Stomach and reduces capacity
    2. Indicated in BMI 27-40 with normal gastrointestinal motility and anatomy
    3. Plenity 3 capsules with 16 ounces water taken 20-30 min before lunch and before dinner
    4. Discontinue use if insignificant weight loss at 2 months
    5. Patients lose 2% more than Placebo in 6 months (similar to Orlistat) at $100 per month
    6. Side Effects include Flatulence and bloating
  7. Bupropion (Wellbutrin)
    1. Results in 6 pound weight loss more than Placebo in one year
  8. Phentermine (Fastin, Lonamin, Lomira)
    1. Results in 5 pound weight loss more than Placebo in one year
    2. May cause Agitation or Insomnia (intolerable in 11%)
    3. Contraindicated in heart disease or Uncontrolled Hypertension
  9. References
    1. (2015) Presc Lett 22(5): 26
    2. (2015) Presc Lett 22(2): 7-8
    3. (2014) Presc Lett 21(11): 62

IX. Contraindications: Noradrenergic agents (all agents other than Orlistat)

X. Drug Interactions

  1. Orlistat
    1. Cyclosporine
    2. Fat soluble Vitamins (see above)
  2. Serotonin Syndrome risk
    1. Lorcaserin (Belviq) when combined with other serotonergic agents
  3. Noradrenergic agents (all except Orlistat)
    1. MAO Inhibitors
    2. Guanethidine
    3. Tricyclic Antidepressants
    4. Alcohol
    5. Centrally acting stimulants or Anorexiants

XI. Adjunctive Therapies

  1. Ursodeoxycholic Acid 600mg qd
    1. Prevention of Gallstones in dieting obese patients
    2. Reference
      1. Shiffman (1995) Ann Intern Med 122:899-905 [PubMed]

XII. Preparations: Pharmacologic Therapies recalled by FDA for CV effects

  1. Fenfluramine
  2. Dexfenfluramine
  3. Sibutramine (Meridia)
  4. Phenylpropanolamine (over-the-counter)
    1. Decongestant that stimulates Adrenergic Receptors
    2. Elevates Blood Pressure

XIII. Preparations: Research Drugs (not approved)

  1. Selective Cannabinoid Type I Blocker
    1. Acomplia (Rimonabant) is first in class
    2. Decreases appetite by blocking Cannabinoid Receptors
    3. May also be effective in Tobacco Cessation
    4. Fernandez (2004) Curr Opin Investig Drugs 5:430-5 [PubMed]
  2. Growth Hormone
    1. No change in body weight
    2. Decreases Body fat 9.2%
    3. Decreased visceral fat 18%
    4. Johanssen (1997) J Clin Endocrinol Metab 82: 727 [PubMed]

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