Pharmacologic Management of Obesity

Publication Date: February 28, 2024

Anti-obesity Medications

Anti-obesity Medications

Objectives of Anti-obesity Medications

Improve the health of patients
  • Improve hyperglycemia, high blood pressure, and abnormal lipid levels.
  • Reduce cardiovascular events.
  • Improve other adverse metabolic, biomechanical, and psychosocial health consequences, with improved quality of life.
  • Reduce mortality.
Improve the weight of patients
  • Weight loss to a clinically meaningful degree that patients and clinicians will embrace initiation of anti-obesity therapy.
  • Weight loss maintenance to a degree that patients and clinicians will persist in adhering to long-term anti-obesity therapy.

TOP 5 TAKEAWAY MESSAGES:
Anti-obesity Drug Development

  1. Targets of current anti-obesity drug development are mainly focused on intervention pathways related to the central nervous system, gastrointestinal systems, and adipose tissue.
  2. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are being combined with other agents as double or triple hormone receptor agonists (e.g., retatrutide).
  3. An emerging concept is that the development of anti-obesity agents must not only reduce fat mass (adiposity) but must also correct fat dysfunction (adiposity-related disease).
  4. Novel agents are becoming more effective and reaching outcomes similar to what is observed with bariatric surgery.
  5. With the exception of anti-obesity agents that are a combination of drugs in a single formulation, limited data exists for combinations of multiple anti-obesity medications.

Treatment

  • Phentermine is a sympathomimetic amine with possible adrenergic side effects and contraindications in patients with cardiovascular disease (CVD).
    • Phentermine hydrochloride (HCl) 8–37.5 mg prescribed in the U.S. is generally equivalent to 6.4–30 mg of phentermine resin marketed outside the U.S.
    • Although not consistent with the prescribing information indicated use, phentermine administration for longer than 12 weeks is supported by clinical data and opinion leaders.
  • Semaglutide is a GLP-1 RA indicated for body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 plus at least 1 obesity-related complication (ORC),or children with obesity (age ≥12) with a BMI at or above the 95th percentile or ≥85th plus an ORC. It is contraindicated in pregnancy, in patients with a personal or family history of medullary thyroid cancer (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).
  • Liraglutide is a GLP-1 RA approved at 1.8 mg per day for treatment of type 2 diabetes mellitus, and at 3.0 mg per day for treatment of obesity with possible gastrointestinal side effects. It is also indicated for children with obesity (age ≥12) with a BMI at or above the 95th percentile or ≥85th plus an ORC. It is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2.
  • Naltrexone/bupropion is a combination of an opioid antagonist and antidepressant, with possible gastrointestinal side effects. It is contraindicated in patients with uncontrolled hypertension, chronic opioid use, seizure disorders, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates and antiepileptic drugs.
  • Phentermine/topiramate is a combination of a sympathomimetic amine and anti-seizure/migraine medication with side effects that include paresthesias and dysgeusia. It is contraindicated in women who may be pregnant. Warnings and precautions include embryo-fetal toxicity, suicidal behavior, ophthalmologic adverse reactions, mood and sleep disorders, cognitive impairment, slowing of linear growth, metabolic acidosis, decrease in renal function, and serious skin reactions.
  • Orlistat is a gastrointestinal lipase inhibitor with possible adverse experiences that include oily rectal discharge and flatus. It is contraindicated in patients with chronic malabsorption syndrome and cholestasis.
  • Orlistat should be taken three times a day with each meal that contains fat. Bupropion/naltrexone should not be taken with high fat meals due to increased absorption.

Effects of Concomitant Medications on Weight

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Anti-obesity Pharmacotherapy

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Supplements and Functional Foods

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Key Points

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