Obesity Medication

Aka: Obesity Medication, Appetite Suppressant, Appetite Depressant, Anti-Obesity Agent, Weight Loss Medication, Medications to Promote Weight Loss

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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. 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
  3. 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. GLP-1 Analogs are most expensive at >$1000/month (negotiated costs by insurance companies are often 50%)
  4. Efficacy
    1. Medications are considered effective by American Gastroenterological Association if weight loss >3%
    2. Orlistat and superabsorbent gels (Plenity, Genesis1000) are associated with only 2% weight loss

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

  1. FDA Schedule 4 Medications
    1. Phentermine (Fastin, Adipex-P, Lonamin, Qsymia)
    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)
    3. Semaglutide
    4. Tirzepatide

V. Medications: GLP-1 Analogs

  1. Semaglutide Injection (Ozempic, Wegovy up to 2.4 mg/week)
    1. Mean weight loss 11 to 13% body weight (at least 5% in most patients) and sustained >1 year while on Semaglutide
      1. NNT 2 for weight loss of at least 10% (NNT 3 for weight loss of at least 15%)
      2. Average weight loss 27 lbs more than Placebo for a 2.4 mg weekly dose over 1 year
    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. Tirzepatide (Mounjaro for DM, Zepbound for non-diabetics)
    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%
      2. Dose 10 mg/week reduced weight 19.5%
      3. Dose 15 mg/week reduced weight 20.9% (average 41 lbs lost more than Placebo in 1 year)
      4. 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
  3. Liraglutide Injection (Saxenda, up to 3 mg/day)
    1. Less effective than Semaglutide
    2. 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)
    3. Mean weight loss 4.8% of total body weight loss while on Liraglutide
      1. Results in 10-12 pound weight loss more than Placebo in one year
      2. NNT 6 for weight loss of at least 10% (NNT 11 for weight loss of at least 15%)
    4. May cause Nausea and rare Hypoglycemia (intolerable in 5%)
    5. Among the most expensive Obesity Medications (>$1000/month)

VI. Medications: Effective Combination Agents

  1. Qsymia (Phentermine and Topiramate)
    1. Mean weight loss 8.5% of total body weight while on medication
      1. NNT 3 for weight loss of at least 10% (NNT 4 for weight loss of at least 15%)
      2. Results in 19-20 pound weight loss more than Placebo at 1 year
    2. May cause decreased cognition, Paresthesias, Tachycardia, Ureteral Stones
      1. Intolerable in 8 to 16% of patients (NNH 10)
    3. Must be tapered gradually (due to risk of Seizure)
    4. Significant Teratogenicity risk (requires Informed Consent, reliable Contraception and monitoring with UPT)
    5. Consider in patients with comorbid Migraine Headaches
  2. Contrave (Bupropion and Naltrexone)
    1. Mean weight loss 3% of total body weight while on max dose 16 mg/180 mg twice daily
      1. NNT 7 for weight loss of at least 10% (NNT 12 for weight loss of at least 15%)
      2. Results in 9 to 10.8 lb (up to 4.9 kg) weight loss more than Placebo in one year
      3. Bupropion (Wellbutrin) alone results in 6 pound weight loss more than Placebo in one year
    2. May cause Nausea (intolerable in up to 12 to 15%, NNH 7)
    3. Contraindicated with concurrent Opioids, or Seizure Disorder, Uncontrolled Hypertension
    4. Suicidality risk (FDA black box warning)
    5. Consider in comorbid Major Depression or Tobacco Abuse

VII. Medications: Stimulants (Amphetamine Derivatives)

  1. General Contraindications for these Noradrenergic Stimulants
    1. Uncontrolled Hypertension
    2. Advanced cardiovascular disease (CAD, CHF, Arrhythmias)
    3. Untreated Hyperthyroidism
    4. Narrow-Angle Glaucoma
    5. Substance Abuse history
  2. 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
  3. 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
    4. Typically combined with other agents for best efficacy
      1. Phentermine and Topiramate (Qsymia, previously Qnexa, see above)
      2. Phentermine 30 mg and Fluoxetine 20 mg daily
  4. Diethylpropion (Amfepramone, Tenuate)
    1. Mean weight loss 5.4% of total body weight while on max dose 75 mg/day
      1. NNT 4 for weight loss of at least 10%
    2. Contraindicated in Uncontrolled Hypertension, cardiovascular disease, untreated Hypothyroidism
    3. Adverse effects (similar to Placebo) include Insomnia, irritability, anxiety

VIII. Medications: Gastrointestinal Agents (Least Effective)

  1. Orlistat (Xenical, Alli)
    1. Typically recommended as a first-line agent among the Obesity Medications (but much less effective than GLP-1 Analogs)
    2. Mean weight loss 2.8% of total body weight while on medication
      1. NNT 7 for weight loss of at least 10%
      2. Results in 7 pound weight loss more than Placebo in one year
    3. May cause Nausea, Diarrhea, Flatulence, 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)
  2. 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
  3. Gelesis100
    1. Similar superabsorbent hydrogel as Plenity
    2. Take 2.25 g (3 capsules) orally with water before lunch and dinner
    3. Average weight loss 2%

IX. Medications: Adjunctive

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

X. Medications: 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

XI. Medications: 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]

XII. 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

XIII. References

  1. (2024) Presc Lett 31(1): 1-2
  2. (2015) Presc Lett 22(5): 26
  3. (2015) Presc Lett 22(2): 7-8
  4. (2014) Presc Lett 21(11): 62
  5. (1998) AOA Treatment Adult Obesity, 2nd edition
  6. Apovian (2015) J Clin Endocrinol Metab 100(2):342–362 [PubMed]
  7. Bagley (2023) Am Fam Physician 108(4): 424-6 [PubMed]
  8. Erlandson (2016) Am Fam Physician 94(5): 361-8 [PubMed]
  9. Frank (1998) J Am Diet Assoc 98:S44-48 [PubMed]
  10. Grunvald (2022) Gastroenterology 163(5):1198-1225 +PMID: 36273831 [PubMed]
  11. Lyznicki (2001) Am Fam Physician 63(11):2185-96 [PubMed]
  12. Rippe (1998) J Am Diet Assoc 98:S9-15 [PubMed]
  13. Speer (1997) Phys Sportsmed 25:94-107 [PubMed]
  14. Yanovski (2002) N Engl J Med 346:593 [PubMed]

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