Pharmacologic Management of Obesity

Publication Date: March 1, 2023

Anti-obesity Medications 

Anti-obesity Medications 

Key Points

  • The US adult obesity prevalence was 41.9% in 2017–March 2020.
  • According to a projection analysis in 2019, ~50% of US adults will have obesity by 2030, with ~25% of adults having severe obesity [body mass index (BMI) ≥35 kg/m2].
  • With the exception of anti-obesity agents that are a combination of drugs in a single tablet or capsule, limited data exists for combination anti-obesity drug therapy.
  • Targets of current anti-obesity drug development are mainly focused on intervention pathways related to the central nervous system, gastrointestinal systems and adipose tissue

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 RA) are being combined with other agents as twincretins (e.g., tirzepatide) and tri-agonists.
  3. Oxyntomodulin acting agents have dual GLP-1 RA and glucagon RA activity.
  4. With the exception of anti-obesity agents that are a combination of drugs in a single formulation, limited data exists for combination anti-obesity drug therapy.
  5. The development of anti-obesity pharmacotherapy is following the path of drug development of other metabolic diseases.

Treatment

  • Phentermine is a sympathomimetic amine with possible adrenergic side effects and contraindications in patients with cardiovascular disease.
    • 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 BMI ≥30 kg/m2 + at least 1 obesity-related complication (ORC), BMI ≥27 kg/m2, 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, multiple endocrine neoplasia (MEN) type 2 and a personal or family history of medullary thyroid cancer (CA).
  • 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 personal or family history of medullary thyroid cancer or Type 2 MEN syndrome.
  • 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, and 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 become pregnant.
  • Liraglutide and phentermine/topiramate can be taken with or without meals.
  • 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

...Effects of Concomitan...

...Concomita...

...itations in the reported effects on body weigh...

...Pharmacotherapy That M...

...Cardiovasc...

...body weight: Some beta-blockers...

...Diabetes Mellit...

...ay increase body weight: Most insulins S...

...ecrease body weight: Metformin Glucagon-like...

...al effects on body weight:Dipeptidyl...

...Metformin May help improv...

...effects on body weight: Combined ora...

...y increase body weight: Glucoc...

...effects on body weight: Progestin contraceptives...

...Anti-seizure Medic...

...ase body weight: Carbamazepine...

...ease body weight: Topiramate...

...e body weight: Some tricyclic antidepressants...

...crease body weight: Bupropion Fluoxet...

...iable effects on body weight: Some tricycl...

...Mood Stabilizers...

...rease body weight: Gabapentin Divalproex Lit...

...able/neutral effects on body weight: Lam...

...Migraine Med...

...increase body weight: Amitriptyline G...

...ecrease body weight: Topiramate Zonis...

...tral effects on body weight: Non-...

...Antipsychot...

...tly increase body weight: Clozapin...

...able effects on body weight: Amisulpride...

...Hyp...

...body weight: Diphenhydramine...

...se risk of sleep-related eating disord...

...limited effects on body weight: Benzodiaz...

...Pain Treatments...

...evers: NSAIDs and acetaminophen: ma...

...Neuropath...

...e body weight: Gabapentin Pregab...

Neutral effect on body weight: Nortriptyline...

...HIV Medications...

...ase body weight: Some highly active antire...

...omposition: May increase abdominal and viscer...

...Chemotherapies and Anti...

...ase body weight: Tamoxifen Cycl...

May decrease body weight:...

...Organ Transplant Medicatio...

...(e.g., prednisone) Corticosteroids may...

...inhibitors (cyclosporin, tacrolim...

...an target of rapamycin (mTOR) inhibitors (sirolimu...

...Obesity and Organ Tran...

Obesity is the most common promoter...


Anti-obesity Medication Summary

...Anti-...

...ave contraindications for hypersen...


...Phentermine HCL (L...


...Orlistat (Alli®,Xen...


...Phentermine/Top...


...Naltrexone/bu...


...Liraglutide (Sax...


...Semaglutide (Wegovy®)...


...No...


...Setmelanotide (I...


...Metreleptin Subc...


Supplements and Functional Foods

...Supple...

...Key Points...


...TO...


...mmon Functional FoodsHaving trouble viewing t...


...OTC Anti-obesity Thera...

...hanism of Action Intestinal lipase...


...of Supplements with Insufficient Human Da...


...oss supplements thought unsafe are available...


...eight Loss Supplements Considered Potentially Un...


Weight Loss Therapies with Mandated Disc...