What is the pharmacological mechanism of phentermine (anorexiant) in inducing weight loss?

From the Guidelines

Phentermine promotes weight loss primarily by acting as an adrenergic agonist that activates the sympathetic nervous system, leading to a decrease in food intake and an increase in resting energy expenditure. This mechanism is supported by a study published in Gastroenterology in 2017 1, which highlights the role of phentermine in promoting weight loss through its effects on the sympathetic nervous system. The study found that phentermine alone (15 mg daily) was associated with a 6.0-kg weight loss at 28 weeks, compared with a placebo.

Some key points to consider when prescribing phentermine include:

• The recommended dosage is 15 to 37.5 mg orally once daily in the morning 1
• Phentermine should not be used with monoamine oxidase inhibitors or other sympathomimetic amines 1
• Common side effects include dry mouth, difficulty sleeping, dizziness, and irritability 1
• Appropriate candidates for phentermine include patients with obesity who need assistance with appetite suppression, particularly those without evidence of active or unstable coronary disease, or uncontrolled hypertension 1

It is essential to use phentermine as part of a comprehensive weight management program that includes dietary changes and increased physical activity, as its effectiveness diminishes over time when used alone. Additionally, patients who have anxiety or insomnia might feel their condition is exacerbated by phentermine, and would not be ideal candidates 1. Overall, phentermine is a useful medication for weight loss, but its use should be carefully considered and monitored due to its potential side effects and limitations.

From the FDA Drug Label

Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and dll-amphetamine). Drugs of this class used in obesity are commonly known as “anorectics” or “anorexigenics. ” It has not been established that the primary action of such drugs in treating obesity is one of appetite suppression since other central nervous system actions, or metabolic effects, may also be involved.

The pharmacological mechanism of phentermine in weight loss is not fully established, but it is known to be a sympathomimetic amine with actions similar to amphetamine. The primary action of phentermine may not be solely appetite suppression, as other central nervous system actions or metabolic effects may also be involved 2 2.

• Key points:
  • Phentermine is a sympathomimetic amine
  • Similar pharmacologic activity to amphetamine
  • Primary action in obesity treatment not fully established
  • May involve appetite suppression, central nervous system actions, or metabolic effects

From the Research

Mechanism of Action

• Phentermine is a noradrenergic sympathetic amine that decreases appetite and increases energy expenditure 3, 4.
• The exact mechanism of phentermine in weight loss is not fully understood, but it is believed to work by manipulating the control of hunger and satiety in the central nervous system 5.
• Phentermine may also have a thermogenic effect, increasing the body's energy expenditure and enhancing weight loss 3.

Efficacy in Weight Loss

• Phentermine has been shown to be effective in promoting weight loss, with studies demonstrating a significant reduction in body weight compared to placebo 3, 6, 4.
• The amount of weight loss achieved with phentermine varies, but it is generally in the range of 3-10% of starting weight 5, 6.
• Phentermine has also been shown to improve metabolic parameters, such as blood pressure, lipid profile, and insulin sensitivity 6, 4.

Combination Therapy

• Phentermine is often used in combination with other medications, such as topiramate, to enhance its weight-loss effects 6, 4.
• The combination of phentermine and topiramate has been shown to be effective in promoting weight loss and improving metabolic parameters, with a significant reduction in body weight and improvement in waist circumference 6, 4.

Safety and Tolerability

• Phentermine is generally well-tolerated, with common side effects including paresthesia, dysgeusia, dry mouth, constipation, and insomnia 6, 4.
• There is no evidence to suggest that phentermine is addictive, and large-scale observational studies have not identified an increased risk of cardiovascular events or elevations in blood pressure 7.