What are the effects of long-term use of Phentermine (phentermine hydrochloride)?

From the Guidelines

Long-term phentermine use is generally not recommended beyond 12 weeks due to concerns about diminishing effectiveness and potential health risks. Phentermine (typically prescribed at doses of 15-37.5 mg daily) is FDA-approved only for short-term use as an adjunct to lifestyle modifications for obesity management, as stated in the 2022 AGA clinical practice guideline on pharmacological interventions for adults with obesity 1. Extended use may lead to tolerance, requiring higher doses for the same effect, and increases the risk of side effects including elevated blood pressure, heart palpitations, insomnia, dry mouth, and constipation.

Some key points to consider when prescribing phentermine include:

• The recommended dosage of phentermine is 15–37.5 mg orally once daily, but dosage should be individualized to achieve adequate response with the lowest effective dose 1.
• Phentermine should be avoided in patients with a history of cardiovascular disease, and blood pressure and heart rate should be monitored periodically while taking phentermine 1.
• If weight management is needed beyond 12 weeks, patients should discuss alternative medications with their healthcare provider, such as Qsymia (phentermine-topiramate), Contrave (naltrexone-bupropion), Wegovy (semaglutide), or Saxenda (liraglutide), which are FDA-approved for longer-term use 1.

Any phentermine treatment should always be accompanied by dietary changes, exercise, and behavioral modifications for sustainable weight management. It is essential to weigh the potential benefits of phentermine against the potential risks and to closely monitor patients for any adverse effects, as recommended in the 2017 white paper AGA: power - practice guide on obesity and weight management, education, and resources 1.

From the FDA Drug Label

Phentermine is indicated only as short-term (a few weeks) monotherapy for the management of exogenous obesity When tolerance to the anorectant effect develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued.

Long-term use of phentermine is not recommended. The drug is indicated for short-term use only, and prolonged use may lead to tolerance, dependence, and increased risk of adverse reactions, including:

• Primary pulmonary hypertension
• Valvular heart disease
• Withdrawal effects
• Abuse and dependence Phentermine should be discontinued if tolerance develops or if the patient experiences any adverse reactions. 2 2

From the Research

Long-Term Phentermine Use

• The efficacy and safety of long-term phentermine use have been studied in several research papers 3, 4, 5.
• A study published in 2021 found that phentermine/topiramate resulted in a significant weight loss of 6.8% over a period of at least 12 months 3.
• Another study published in 2024 suggested that phentermine use is associated with clinically significant weight loss in adults and is generally well tolerated, but noted that there is limited rigorous research to support its efficacy and safety in long-term treatment 4.
• A 2019 study found that longer-term users of phentermine experienced more weight loss, with patients using continuously for > 12 months losing 7.4% more than the referent group at 24 months, without an increased risk of incident cardiovascular disease or death 5.

Safety and Effectiveness

• The safety and effectiveness of phentermine have been evaluated in several studies, with findings suggesting that it is generally well tolerated and effective for weight loss 4, 5.
• A 2017 review of pharmacotherapies for obesity management noted that phentermine is approved for short-term use, but can be used off-label for longer-term treatment 6.
• The FDA has approved several anti-obesity medications, including phentermine, for chronic weight management, but notes that they should be used in conjunction with lifestyle modifications and under the guidance of a healthcare professional 3, 7.

Clinical Considerations

• When considering long-term phentermine use, clinicians should weigh the benefits and risks of treatment, taking into account individual patient factors such as comorbidities, preferences, and lifestyle modifications 3, 4.
• Phentermine should be prescribed with the intention of long-term use, as part of a comprehensive treatment plan for obesity management 7.
• Regular monitoring and follow-up are necessary to assess the effectiveness and safety of phentermine treatment, and to make adjustments to the treatment plan as needed 5, 6.