What are alternative weight loss medications for patients with a history of hypertriglyceridemia who cannot use Glucagon-like peptide-1 (GLP-1) agonists?

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Last updated: July 5, 2025View editorial policy

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From the Guidelines

For patients with a history of hypertriglyceridemia who cannot use GLP-1 agonists, phentermine/topiramate extended-release is a recommended alternative weight loss medication, starting at 3.75/23 mg daily and titrating up to 15/92 mg daily, as it has been shown to promote significant weight loss without worsening triglyceride levels 1. When considering alternative weight loss medications, it's essential to evaluate the potential effects on triglyceride levels. Phentermine/topiramate extended-release has been found to be effective in promoting weight loss, with studies such as EQUIP and CONQUER demonstrating its efficacy in achieving significant weight loss compared to placebo 1. Key points to consider when prescribing phentermine/topiramate extended-release include:

  • Starting dose: 3.75/23 mg daily, with gradual titration up to 15/92 mg daily as needed and tolerated
  • Mechanism of action: combines an appetite suppressant (phentermine) with an anticonvulsant (topiramate) that promotes satiety
  • Potential side effects: monitor for adverse effects such as dry mouth, dizziness, and insomnia
  • Importance of lifestyle modifications: emphasize the need for a balanced diet and regular exercise in conjunction with medication therapy Other alternative medications, such as orlistat (Xenical) and naltrexone-bupropion (Contrave), may also be considered, but phentermine/topiramate extended-release is a preferred option due to its efficacy and safety profile in patients with hypertriglyceridemia 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Alternative Weight Loss Medications

When GLP-1 agonists are contraindicated due to a history of hypertriglyceridemia, several alternative weight loss medications can be considered. These include:

  • Orlistat: a lipase inhibitor that reduces fat absorption in the gut 2, 3
  • Phentermine: a sympathomimetic amine that suppresses appetite, although it should be used with caution in patients with cardiovascular disease 2, 4, 3
  • Lorcaserin: a serotonin receptor agonist that reduces hunger and increases feelings of fullness, which has been shown to be safe in patients with cardiovascular disease 2, 4

Considerations for Treatment

When selecting an alternative weight loss medication, it is essential to consider the patient's medical history, potential side effects, and the efficacy of the medication. For example:

  • Orlistat can cause gastrointestinal side effects, such as diarrhea and abdominal pain 3
  • Phentermine can increase heart rate and blood pressure, and has the potential for dependency 4, 3
  • Lorcaserin has been associated with serious harms, including valvular heart disease and euphoria, although it has been shown to be safe in patients with cardiovascular disease 2, 4

Future Directions

Research is ongoing to develop new and effective oral weight loss medications, including oral GLP-1 receptor agonists such as semaglutide, danuglipron, and orforglipron 5. These medications have the potential to increase availability and accessibility for patients with obesity, and may offer a more convenient alternative to injectable medications.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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