Does diethylpropion (amfepramone) work for weight loss?

While obesity in the United States has increased over the last five decades, more and more people are determined to commit to healthier lives and embark on weight loss journeys. While healthcare providers favor lifestyle changes like diet changes and regular exercise for boosting weight loss, these changes aren’t enough to produce meaningful weight loss for some people. As a result, many people visit a healthcare provider to seek medications to aid in weight loss. One such medication is diethylpropion, also known as amfepramone, and available under the brand names Anorex, Linea, Nobesine, Prefamone, Regenon, Tepanil, and Tenuat. 

Keep reading to learn about diethylpropion, how well it works for weight loss, as well as risks, potential side effects, and more. 

Diethylpropion is a prescription medication that was approved by the FDA in 1959 for short-term weight management treatment. Brand-name versions include Tenuate, Tenutate Dospan, and Tepanil. It’s used for the short-term treatment of obesity in adults with a body mass index (BMI) of 30 or greater who haven’t seen significant weight with diet and exercise alone. Diethylpropion is meant to be used in combination with a low-calorie diet for a short period of time: typically up to 12 weeks.

Diethylpropion is a type of appetite suppressant. It works by making you feel more full and reducing your desire to eat. Diethylpropion is a stimulant drug, but unlike other stimulants (like Adderall), has less of an effect on your central nervous system, giving it a relatively lower abuse potential than some other stimulants.

A higher BMI generally indicates more body fat and a higher risk of health consequences. However, note that other factors can influence BMI. For instance, having a lot of muscle mass can result in a high BMI in a person that isn’t necessarily obese.

The CDC defines obesity as having a BMI greater than 30 kg/m2. There are three classes of obesity: 

• Class 1: BMI of 30 to < 35

• Class 2: BMI of 35 to < 40

• Class 3: BMI of 40 or greater 

That said, diethylpropion is specifically FDA-approved for adults with Class 1, 2, or 3 obesity who have failed to lose weight with diet and exercise efforts alone.

Although diethylpropion is not meant to be used for longer than 12 weeks, some healthcare providers prescribe it long-term “off-label.” Off-label prescribing refers to prescribing a medication differently than what is specified on the drug’s official labeling document (prescribing information or PI) as approved by the FDA. Off-label prescribing is a common practice in medicine but depends on the discretion of an experienced healthcare provider.

Diethylpropion elicits its therapeutic effect by working in your central nervous system. In scientific terms, diethylpropion is classified as a sympathomimetic stimulant drug. It works to activate the body’s sympathetic nervous system, which is responsible for your fight-or-flight response. Stimulating this response causes your body to release neurotransmitters responsible for regulating your appetite. Examples of these neurotransmitters include norepinephrine, dopamine, and serotonin. 

Through this mechanism, diethylpropion can also boost your body’s ability to burn calories. By increasing energy usage and burning more fat, diethylpropion can aid in weight loss. By stimulating your nervous system, diethylpropion also reduces appetite by increasing feelings of fullness—which can help a person adhere to a lower-calorie diet. 

How long does diethylpropion take to work?

Typically, people using diethylpropion see weight loss of at least four pounds within the first four weeks of treatment. Your healthcare provider might set a different goal for you. If the drug doesn’t seem to be helping within the first month or so, they may have you stop taking it due to lack of response. If you’re steadily losing weight, your healthcare provider may decide to continue the treatment for up to 12 weeks, or even longer in some cases. 

Does diethylpropion actually work? A look at the evidence

In combination with a low-calorie diet, taking diethylpropion has been effective in helping patients lose weight compared to placebo in various clinical trials. In a 1975 study of 102 people with obesity, those treated with diethylpropion lost significantly more weight than those treated with a placebo after eight weeks of treatment. Those who took diethylpropion lost an average of 11.1 pounds (6.4% of their initial weight), while those who took a placebo lost an average of 6.2 pounds (3.6% of their starting weight).

Another study in 1981 compared the extended-release form of diethylpropion to placebo in 49 patients with obesity. This study found that the drug led to significant weight loss compared to placebo. Those treated with diethylpropion saw an average weight loss of 15.9 pounds after 12 weeks, averaging 1.32 pounds of weight loss per week. Those treated with a placebo experienced an average weight loss of 10 pounds after 12 weeks, about 0.84 pounds weekly. 

A 2009 study assessed longer-term use of diethylpropion in 69 patients with obesity. Those who were treated with diethylpropion lost an average of 9.8% of their body weight within six months, while those in the placebo group had an average weight loss of 3.2%. At 12 months, those treated with diethylpropion saw a 10.6% decrease in body weight. After the six-month mark, those treated with a placebo from months 1 through 6 were switched to diethylpropion for months 6 through 12. These patients lost an average of 7% of their initial body weight at 12 months. These results show that diethylpropion, in combination with a low-calorie diet, produced a lasting reduction in body weight over one year.

A 2005 meta-analysis looked at nine placebo-vs-diethylpropion trials and found the drug was associated with modest weight loss. 

While the evidence seems encouraging from a weight-loss perspective, you may be wondering about the downsides. Keep reading to learn about the potential side effects that make diethylpropion a less desirable option for many people.

Diethylpropion can cause side effects, many of which are unpleasant or even dangerous. As a result, it is not prescribed very often by healthcare providers. In general, due to its risks, the drug is used sparingly in clinical practice. 

Common side effects of diethylpropion may include:

• Dizziness

• Taste changes

• Restlessness or anxiety

• Dry mouth

• Tremor

• Stomachache

• Nausea

• Vomiting

• Increased urination

• Sore throat

• Insomnia (trouble sleeping)

One of the clinical studies described in the previous section reported that the diethylpropion’s side effects were minimal, though, and described few to no amphetamine-like side effects, which can include anxiety, tremors, irritability, and behavior issues. If drug side effects become bothersome, speak with your healthcare provider to discuss alternative options.

Serious side effects of diethylpropion can include:

• Palpitations 

• Rapid heartbeat

• Irregular heartbeat

• High blood pressure

• Chest pain or discomfort

• Vision changes

• Difficulty breathing

• Swelling of the ankles or feet

• Loss of consciousness

• Itching

• Rash

• Painful urination

• Fever

• Allergic reaction

If you experience a serious side effect, seek medical attention immediately.  

The typical dosage of diethylpropion is 75 mg per day. Be sure to follow your healthcare provider’s instructions. The drug is available in two forms: a 25 mg immediate-release oral tablet and a 75 mg extended-release tablet. The immediate-release tablet is typically taken three times daily, an hour before each meal. The extended-release type is typically taken just once daily.

Here are some tips for taking diethylpropion: 

• Do not chew, crush, or cut extended-release diethylpropion tablets. Swallow them whole with water.

• Store diethylpropion in a cool, dry place at room temperature. Keep this and all medications out of reach of children and pets.  

• If you miss a dose of diethylpropion, take the next dose as soon as you remember. If it is almost time to take your next scheduled dose, you can skip the missed dose and only take one tablet. Do not take two pills at once to double up for a missed dose. Do not take more diethylpropion than prescribed.

Setting an alarm or reminder notification on your phone can help you remember to take your medication on time. Likewise, a pill organizer can help you keep track of each dose. 

Diethylpropion may interact with certain medications. Tell your healthcare provider all prescriptions, dietary supplements, and over-the-counter medications you are currently taking before starting diethylpropion.

The following types of drugs may interact with diethylpropion:

Anorectic agents (Diet Pills): Prescription, supplement, and over-the-counter weight loss medications may cause serious, life-threatening lung and blood pressure problems. To be safe, avoid taking more than one type of “diet pill” and tell your provider about any diet pills you’ve tried in the last year.

Monoamine oxidase inhibitors (MAOI): Taking MAO inhibitors (MAOI, such as linezolid, phenelzine, or selegiline) increases the risk of extremely high blood pressure and heart problems. Do not take diethylpropion for at least 14 days after stopping an MAOI drug.

Insulin: Diethylpropion can alter blood sugar levels and hide symptoms of low blood sugar. If you have diabetes, monitor your blood sugar more closely while taking this medication.

General anesthetics or benzodiazepine medications: Diethylpropion with general anesthetics (like propofol, Ativan, or Valium) may result in abnormal heart rhythm. If you’ll need surgery or anesthesia while taking diethylpropion, don’t forget to tell the surgeon about all medications you are currently taking.

Alcohol and CNS depressants: Diethylpropion may increase the effects of alcohol and drugs that slow the central nervous system (CNS depressants), leading to excessive drowsiness. Examples of CNS depressant drugs are sedatives like Ambien, opioids such as codeine, and benzodiazepines like Xanax.

Muscle relaxants: Diethylpropion can increase the effects of muscle relaxants (such as cyclobenzaprine or carisoprodol), causing excessive weakness.

Seizure medications: Diethylpropion may increase the risk of seizures in people with epilepsy or a seizure disorder.

This list is not an all-encompassing list of diethylpropion interactions. Discuss with your healthcare provider to determine if diethylpropion interacts with any of your medications.

Diethylpropion isn’t safe for everyone. People with the following conditions may be at higher risk for side effects if they take this medication:

Diabetes: If you have diabetes, be aware that diethylpropion may affect your blood sugar levels. Diethylpropion may hide the warning symptoms of low blood sugar. Check your blood sugar regularly and let your healthcare provider know if your blood sugar changes.

Blood pressure or heart disease: Diethylpropion should not be taken by people with heart disease, abnormal heart rhythm, or hypertension (high blood pressure). Diethylpropion may make these conditions worse.

Epilepsy: Diethylpropion may increase convulsions and the risk of seizures in people with epilepsy.

Thyroid disorders: Diethylpropion may cause overactive thyroid and should be avoided in people with thyroid disorders.

Glaucoma: The drug can worsen glaucoma (elevated pressure in the eye) and isn’t recommended for people with this condition.

History of drug abuse: Diethylpropion can be habit-forming. It isn’t recommended for people with a history of drug addiction or abuse.

Pregnancy or breastfeeding: It isn’t known for sure if diethylpropion causes birth defects, but it’s not recommended for use during pregnancy. Taking diethylpropion during pregnancy may result in withdrawal symptoms in the baby after birth. Avoid diethylpropion if you are pregnant or trying to conceive. In addition, diethylpropion passes into breast milk if taken by a nursing mother. The risks of breastfeeding while taking diethylpropion should be discussed with your healthcare provider.

After reading the potential risks and warnings, you may be interested in learning more about other weight-loss medications besides diethylpropion.

Guidelines from the American Gastroenterological Association (AGA) recommend how physicians should approach prescribing medications for patients with obesity. These guidelines begin by recommending lifestyle changes, like diet and exercise, before considering a weight loss drug. If lifestyle changes aren’t enough, a healthcare provider may recommend a weight loss medication for you, depending on your BMI and overall health status. 

Specifically, the AGA recommends semaglutide injection (brand names: Ozempic, Wegovy) as the first-line treatment due to its average weight loss results of more than 10.8%. Other first-line options include liraglutide injections (Saxenda), phentermine/topiramate extended-release capsules (Qsymia), or naltrexone/bupropion extended-release tablets (Contrave). 

If the first-line options do not work, your provider might prescribe diethylpropion or phentermine as a second-line treatment. Both drugs are indicated for short-term use only, but the AGA notes that diethylpropion or phentermine may be prescribed for longer than 12 weeks if deemed necessary and closely supervised by a licensed healthcare provider.

Recent media has put much attention on glucagon-like peptide (GLP-1) agonist drugs like Ozempic and Wegovy for weight loss. Both contain the active ingredient semaglutide and are injected once a week. Semaglutide was initially approved in 2017 for lowering blood sugar in adults with type 2 diabetes and can help people lose significant weight. It’s also been shown to reduce the risk of serious complications in adults with type 2 diabetes and heart disease. All GLP-1 agonist medications are intended to be used in combination with lifestyle changes, including a low-calorie diet and increased physical activity.

Your healthcare provider can help you establish timeframes to check your weight and set realistic expectations for your goals. If a weight-loss medication doesn’t result in a 5% reduction in total body weight, or if weight-related complications aren’t able to be adequately controlled, the AGA considers the treatment a “failure.” (Not the person!) If the treatment fails, your healthcare provider may suggest switching to a different weight loss medication. Alternatively, bariatric surgery may be recommended.

Diethylpropion should be taken alongside a low-calorie diet to see the best results. Following a low-calorie diet can help you see results more quickly. If you’re wondering whether to cut out fat, carbohydrates, or both, a low-carb diet generally produces better results than a low-fat diet in the first few months of changing eating habits. Regardless of the diet you choose to follow, aiming to eat less processed foods is always a good idea for nourishing your body. 

You might feel overwhelmed by coming up with a personalized eating plan for your goals and needs. Consult with a professional such as a registered dietitian or weight loss specialist to find a plan that works for you. These services may even be covered by health insurance.

In addition to a healthy diet, exercise can also yield positive results. The CDC recommends 150 minutes of moderate-intensity physical exercise weekly, with two days of muscle-strengthening activity. Not all exercise has to be strenuous; even walking for 30 minutes a day for five days a week can help you reach this goal. If you need help with an exercise plan or find exercise to be painful, reach out to a healthcare provider, physical therapist, or certified personal trainer to help find a plan that’s right for your level of fitness.

While diethylpropion is intended for the short-term management of obesity, maintaining a healthy diet and exercising regularly are long-term interventions that can be used to maintain a healthy body weight.

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Current version

August 18, 2023

Written by

Patricia Weiser, PharmD

Fact checked by

Yael Cooperman, MD

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About the medical reviewer

Yael Cooperman, MD, Ro

Yael Cooperman is a physician and works as a Senior Manager, Medical Content & Education at Ro.