Obesity Medication

Updated: May 06, 2021
  • Author: Osama Hamdy, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Medication Summary

Few medications are available for the management of obesity. Generally, the medications approved by the US Food and Drug Administration (FDA) for obesity are intended for patients with a BMI of 30 or above (obese) or of 27 or above (overweight) with a weight-related risk factor (eg, diabetes, hypertension). All are indicated as adjuncts to caloric restriction, increased physical activity, and behavior modification.

Some examples of obesity medications include orlistat (Xenical [Rx], Alli [OTC]), a fixed-dose combination of immediate-release phentermine and extended-release topiramate (Qsymia), and a fixed-dose combination of bupropion and naltrexone (Contrave).

However, the list of potential antiobesity agents being investigated has increased considerably with the explosion in knowledge of the pathogenesis of obesity. Improved understanding of the neurocircuitry of the feeding-satiety cycle has provided many potential targets for designer therapeutic agents under development. (See the diagram below.)

Central nervous system neurocircuitry for satiety Central nervous system neurocircuitry for satiety and feeding cycles.

Currently, the 3 major groups of drugs used to manage obesity are as follows:

  • Centrally acting medications that impair dietary intake

  • Medications that act peripherally to impair dietary absorption

  • Medications that increase energy expenditure

Setmelanotide is the first drug approved for weight management in patients with rare genetic conditions (ie, proopiomelanocortin [POMC], proprotein convertase subtilisin/kexin type 1 [PCSK1], leptin receptor [LEPR] deficiencies).

Most medications for obesity are approved for short-term use only. Available literature indicates that their utility is severely limited when they are given in this fashion. Obesity is a chronic medical condition, and as with similar chronic conditions (eg, diabetes, hypertension), after therapeutic agents are stopped, the relapse rate is high. The need for any pharmaceutical regimen to be combined with a sustained exercise, dietary adjustment, and behavioral-change regimen to sustain weight loss further complicates the successful management of obesity.


Gastrointestinal Agents, Other

Class Summary

Lipase inhibitors may induce weight loss by inhibiting nutrient absorption.

Orlistat (Xenical, Alli)

Orlistat is a gastrointestinal and pancreatic lipase inhibitor that induces weight loss by inhibiting dietary fat absorption. Orlistat should be taken during or up to 1 hour after a meal containing fat. Its effectiveness in producing weight loss does not depend on systemic absorption. Orlistat is available over the counter (Alli) in a half-strength dose and as a prescription drug (Xenical) as a full-strength dose.

Orlistat may reduce absorption of some fat-soluble vitamins (A, D, E, K) and beta carotene. Administer a multivitamin supplement containing fat-soluble vitamins orally daily, 2 hours before or 1 hour after a meal. Orlistat may also affect the absorption of some medications. In particular, patients on warfarin need closer monitoring because of the potential for malabsorption of vitamin K.

At the full dose of 120 mg 3 times daily, Xenical is frequently associated with such adverse GI events as flatulence, oily stool, diarrhea, and stool incontinence. Frequently, these adverse events result from the common misconception that because orlistat blocks fat absorption, people can consume more fat. It is important to advise patients to reduce total fat intake while on orlistat to reduce the frequency and severity of adverse events.

Doses of the over-the-counter form of orlistat, Alli (60 mg), are associated with fewer adverse events. However, this dosage is less effective for weight loss.


CNS Stimulants, Anorexiants

Class Summary

Anorexiants are administered to manage obesity. Indications include weight loss and maintenance of weight loss, in conjunction with a reduced-calorie diet, specifically in patients who have an initial body mass index (BMI) of 30 or more (obese) or a BMI of 27 or more (overweight) and other risk factors (eg, diabetes mellitus, dyslipidemia, hypertension).

Adrenergic agonists that release tissue stores of epinephrine, causing subsequent alpha- and/or beta-adrenergic stimulation, have provided benefits to patients with obesity. Response to therapy should be evaluated by week 12. If a patient has not lost at least 5% of baseline body weight, stimulants should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

Lorcaserin (Belviq, Belviq XR)

February 13, 2020: The FDA requested that lorcaserin be withdrawn from the market owing to a potential risk of cancer.

Lorcaserin is indicated as an adjunct to a reduced-calorie diet and exercise for long-term weight management in patients with an initial BMI of ≥30 (obese) or in those with a BMI of ≥27 (overweight) who have at least 1 weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes mellitus).

The exact mechanism of action of lorcaserin is unknown, but this agent is thought to decrease food consumption and promote satiety by selectively activating 5-HT2C receptors on anorexigenic pro-opiomelanocortin neurons located in the hypothalamus.

Phentermine/topiramate (Qsymia)

This low-dose combination of phentermine, a sympathomimetic amine anorectic, and extended-release topiramate, an antiepileptic drug that possibly suppresses appetite and enhances satiety. The drug combination is indicated as an adjunct to a reduced-calorie diet and increased physical activity for long-term weight management in adults.

Phentermine (Adipex P, Lomaira)

Phentermine is a sympathomimetic amine that increases the release and reuptake of norepinephrine and dopamine. Its anorexiant effect occurs as a result of satiety-center stimulation in hypothalamic and limbic areas of the brain.

As a pharmacologic component of a comprehensive weight-reduction program (including behavioral modification, caloric restriction, and exercise), phentermine is intended for patients with an initial BMI of ≥30 (obese). It is also appropriate for patients with a BMI of ≥27 (overweight) who have other risk factors (eg, diabetes, hyperlipidemia, hypertension).

Phentermine is indicated for patients aged ≥16 y. It is available in capsules, tablets, and orally disintegrating tablets. This medication is contraindicated for use in pregnant women.


Diethylpropion is indicated for use as a short-term adjunct in the management of obesity. It is a sympathomimetic amine that reduces appetite, an effect that appears to be secondary to CNS effects. It is available in a 24-hour controlled-release formulation that should be taken at midmorning. It is indicated for patients aged ≥16 y.

Phendimetrazine (Bontril PDM)

Phendimetrazine is indicated for use as a short-term adjunct in the management of obesity in patients aged ≥17 y. It is a sympathomimetic amine that reduces appetite, an effect that appears to be secondary to CNS effects.

This agent is available in a 24-hour slow-release 105 mg capsule, which should be taken in the morning 30-60 minutes before breakfast. It is also available in 17.5-35 mg tablets, which should be taken 2 or 3 times daily and an hour before a meal. The maximum recommended dose is 70 mg TID. Phendimetrazine is contraindicated during pregnancy.

Benzphetamine (Regimex)

Benzphetamine is a sympathomimetic amine that reduces appetite, an effect that appears to be secondary to CNS effects. It is used as a short-term adjunct to caloric restriction in exogenous obesity. It is indicated for use in patients aged ≥12 y; the maximum dose is 50 mg TID. This medication is contraindicated during pregnancy.


Glucagon-like Peptide-1 Agonists

Class Summary

GLP-1 agonists have shown to promote weight loss in patient with or without type 2 diabetes mellitus.

Liraglutide (Saxenda)

Liraglutide is a glucagonlike peptide-1 (GLP-1) analog. GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. It is indicated for chronic weight management as an adjunct to diet and exercise in adults with a BMI of ≥30 (obese) or adults with a BMI of ≥27 (overweight) who have at least 1 weight-related condition (eg, hypertension, type 2 diabetes, dyslipidemia).


Antidepressants, dopamine reuptake inhibitors; opioid antagonists

Class Summary

These agents may cause a reduction in appetite and increase in energy expenditure by increasing activity of pro-opiomelanocortin (POMC) neurons.

Bupropion and naltrexone (Contrave)

Bupropion: Increases dopamine activity in the brain, which appears to lead to a reduction in appetite and increase in energy expenditure by increasing activity of pro-opiomelanocortin (POMC) neurons

Naltrexone: Blocks opioid receptors on the POMC neurons, preventing feedback inhibition of these neurons and further increasing POMC activity

Combination may regulate activity in the dopamine reward system of the brain that helps control food cravings and overeating behaviors


Melanocortin Agonists

Class Summary

Melanocortin-4 (MC4) receptors in the brain are involved in the regulation of hunger, satiety, and energy expenditure. Setmelanotide may reestablish MC4-receptor pathway activity in patients with obesity due to rare genetic conditions associated with insufficient activation of the MC4 receptor.

Setmelanotide (Imcivree)

MC4 agonist designed to restore impaired MC4 pathway function caused by genetic variants that occur upstream of the receptor. It is indicated for adults and for children aged 6 years or older, being employed for chronic weight management in obesity resulting from proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency.