Section 3.3 Weight-Loss Medications

Key Points

  • Older obesity pharmacotherapies are limited by tolerability and dependence issues and are approved only for short-term use (≤12 weeks).
  • Newer weight loss agents are typically better tolerated, have better safety profiles, and are approved for chronic weight management including weight maintenance.
  • Pharmacotherapy for overweight and obesity should be used only as an adjunct to lifestyle therapy and not alone.

AACE/ACE Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity Recommendation1

Short-term Therapy

  • R79. Pharmacotherapy should be offered to patients with obesity, when potential benefits outweigh the risks, for the chronic treatment of the disease. Short-term treatment (3 to 6 months) using weight-loss medications has not been demonstrated to produce longer-term health benefits and cannot be generally recommended based on scientific evidence.

Choice of Weight-Loss Agent

  • R80. In selecting the optimal weight-loss medication for each patient, clinicians should consider differences in efficacy, side effects, cautions, and warnings that characterize medications approved for chronic management of obesity, and the presence of weight-related complications and medical history; these factors are the basis for individualized weight-loss pharmacotherapy; a generalizable hierarchical algorithm for medication preferences that would be applicable to all patients cannot currently be scientifically justified.
  • R81. Clinicians and their patients with obesity should have access to all approved medications to allow for the safe and effective individualization of appropriate pharmacotherapy.

Combinations of Weight-Loss Medications

  • R82. Combinations of FDA-approved weight-loss medications should only be used in a manner approved by the FDA or when sufficient safety and efficacy data are available to assure informed judgment regarding a favorable benefit-to-risk ratio.

Agent Selection for Specific Clinical Conditions

Chronic Kidney Disease

  • R83. Weight-loss medications should not be used in the setting of end-stage renal failure, with the exception that orlistat and liraglutide 3 mg can be considered in selected patients with a high level of caution.
  • R84. The use of naltrexone extended release (ER)/bupropion ER, lorcaserin, or phentermine/topiramate ER is not recommended in patients with severe renal impairment (<30 mL/min).
  • R85. All weight-loss medications can be used with appropriate cautions in patients with mild (50 to 79 mL/min) and moderate (30 to 49 mL/min) renal impairment, except that in moderate renal impairment the dose of naltrexone ER/bupropion ER should not exceed 8 mg/90 mg twice per day, and the daily dose of phentermine/topiramate ER should not exceed 7.5 mg/46 mg.
  • R86. Orlistat should not be used in patients with, or at risk of, oxalate nephropathy. Liraglutide 3 mg should be discontinued if patients develop volume depletion, for example, due to nausea, vomiting, or diarrhea.

Nephrolithiasis

  • R87. Naltrexone ER/bupropion ER, lorcaserin, and liraglutide 3 mg are preferred weight-loss medications in patients with a history, or at risk, of nephrolithiasis. Caution should be exercised in treating patients with phentermine/topiramate ER and orlistat who have a history of nephrolithiasis.

Hepatic Impairment

  • R88. All weight-loss medications should be used with caution in patients with hepatic impairment and should be avoided in severe hepatic impairment (i.e., Child-Pugh score >9).
  • R89. Dose adjustments for some medications are warranted in patients with moderate hepatic impairment specifically, the maximum recommended dose of naltrexone ER/bupropion ER is 1 tablet (8 mg/90 mg) in the morning; the maximum recommended dose of phentermine/ topiramate ER is 7.5 mg/46 mg daily.
  • R90. Clinicians should maintain a high index of suspicion for cholelithiasis in patients undergoing weight-loss therapy, regardless of the treatment modality; in high-risk patients, liraglutide 3 mg should be used with caution; effective preventive measures include a slower rate of weight loss, an increase in dietary fat, or administration of ursodeoxycholic acid.

Hypertension

  • R91. In patients with existing hypertension, orlistat, lorcaserin, phentermine/topiramate ER, and liraglutide 3 mg are preferred weight-loss medications. Heart rate should be carefully monitored in patients receiving liraglutide 3 mg and phentermine/topiramate ER. Naltrexone ER/bupropion ER should be avoided if other weight-loss medications can be used because weight loss assisted by naltrexone ER/bupropion ER cannot be expected to reduce blood pressure, and the drug is contraindicated in uncontrolled hypertension.

Cardiovascular Disease and Cardiac Arrhythmia

  • R94. In patients with established atherosclerotic cardiovascular disease, orlistat and lorcaserin are preferred weight-loss medications. Liraglutide 3 mg, phentermine/topiramate ER, and naltrexone ER/bupropion ER are reasonable to use with caution, and to continue if weight-loss goals are met, with careful monitoring of heart rate and blood pressure. Cardiovascular outcome trials are planned or ongoing for all weight-loss medications except orlistat.
  • R95. Orlistat and lorcaserin are preferred weight-loss medications in patients with a history or risk of cardiac arrhythmia. Naltrexone ER/bupropion ER, liraglutide 3 mg, and phentermine/topiramate ER are not contraindicated but should be used cautiously with careful monitoring of heart rate and rhythm.

Depression With or Without Selective Serotonin Reuptake Inhibitor Therapy

  • R96. All patients undergoing weight-loss therapy should be monitored for mood disorders, depression, and suicidal ideation.
  • R97. Orlistat, liraglutide 3 mg, and phentermine/topiramate ER at initiation (3.75 mg/23 mg) and low treatment (7.5 mg/46 mg) doses may be considered in patients with obesity and depression.
  • R98. Lorcaserin and naltrexone ER/bupropion ER should be used with caution in patients with obesity and depression or avoided if patients are taking medications for depression.

Anxiety

  • R99. Maximal dose (15 mg/92 mg) phentermine/topiramate ER should be used with caution in patients with obesity and anxiety disorders.

Psychotic Disorders With or Without Medications

  • R100. Patients with psychotic disorders being treated with antipsychotic medications (lithium, atypical antipsychotics, monoamine oxidase inhibitors) should be treated with a structured lifestyle intervention to promote weight loss or prevent weight gain.
  • R101. Treatment with metformin may be beneficial in promoting modest weight loss and metabolic improvement in individuals with psychotic disorders who are taking antipsychotic medications.
  • R102. Caution must be exercised in using any weight-loss medication in patients with obesity and a psychotic disorder due to insufficient current evidence assessing safety and efficacy.

Eating Disorders Including Binge Eating Disorder

  • R104. Patients with overweight or obesity who have binge eating disorder should be treated with a structured behavioral/lifestyle program in conjunction with cognitive behavioral therapy or other psychological interventions.
  • R105. In patients with overweight or obesity and binge eating disorder, treatment with orlistat or approved medications containing topiramate or bupropion may be considered in conjunction with structured lifestyle therapy, cognitive behavioral therapy, and/or other psychological interventions.
  • R106. Structured lifestyle therapy and/or selective serotonin reuptake inhibitor therapy may be considered in patients with obesity and night eating syndrome.

Glaucoma

  • R107. Liraglutide 3 mg, orlistat, and lorcaserin are preferred weight-loss medications in patients with a history, or at risk of, glaucoma. Phentermine/topiramate ER should be avoided and naltrexone ER/bupropion ER used with caution in patients with glaucoma.

Seizure Disorder

  • R108. Phentermine/topiramate, lorcaserin, liraglutide, and orlistat are preferred weight-loss medications in patients with a history, or at risk, of seizure/epilepsy. The use of naltrexone ER/bupropion ER should be avoided in these patients.
  • R109. All patients with obesity should be monitored for typical symptoms of pancreatitis (e.g., abdominal pain or gastrointestinal [GI] distress) due to a proven association between these diseases.
  • R110. Patients receiving glyburide, orlistat, or incretin-based therapies (glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase 4 inhibitors) should be monitored for the development of pancreatitis. Glyburide, orlistat, and incretin-based therapies should be withheld in cases of prior or current pancreatitis; otherwise there are insufficient data to recommend withholding glyburide for glycemic control, orlistat for weight loss, or incretin-based therapies for glycemic control or weight loss due to concerns regarding pancreatitis.

Opioid Use

  • R111. In patients requiring chronic administration of opioid or opiate medications, phentermine/topiramate ER, lorcaserin, liraglutide 3 mg, and orlistat are preferred weight-loss medications, while naltrexone ER/bupropion ER should not be used.

Women of Reproductive Potential

  • R112. Weight-loss medications must not be used in pregnancy.
  • R113. All weight-loss medications should be used in conjunction with appropriate forms of contraception in women of reproductive potential.
  • R114. Weight-loss medications should not be used in women who are lactating and breast-feeding.

The Elderly, ≥65 years

  • R115. Elderly patients (≥65 years) should be selected for weight-loss therapy involving structured lifestyle interventions that include reduced-calorie meal plans and exercise, with clear health-related goals in mind that include prevention of type 2 diabetes (T2D) in high-risk patients with prediabetes, blood pressure lowering, and improvements in osteoarthritis, mobility, and physical function.
  • R116. Elderly patients with overweight or obesity being considered for weight-loss therapy should be evaluated for osteopenia and sarcopenia.
  • R117. Weight-loss medications should be used with extra caution in elderly patients with overweight or obesity; additional studies are needed to assess efficacy and safety of weight-loss medications in the elderly.

Addiction/Alcoholism

  • R118. In patients with obesity and alcohol or other addictions, consider using orlistat or liraglutide 3 mg. Lorcaserin (abuse potential due to euphoria at suprapharmacologic doses) and naltrexone ER/bupropion ER (lowers seizure threshold) should be avoided in patients with alcohol abuse, and naltrexone ER/bupropion ER is contraindicated during alcohol withdrawal.

Post-Bariatric Surgery

  • R119. Patients that have undergone bariatric surgery should continue to be treated with an intensive lifestyle intervention. Patients that have regained excess weight (≥25% of the lost weight), have not responded to intensive lifestyle intervention, and are not candidates for reoperation may be considered for treatment with liraglutide (1.8 to 3.0 mg) or phentermine/topiramate ER; the safety and efficacy of other weight-loss medications have not been assessed in these patients.

Reference

  1. Garvey WT, Mechanick JL, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients With Obesity. Endocr Pract. 2016;22(suppl 3);1-205.