Phentermine and semaglutide: can you combine these weight loss drugs?

Semaglutide and phentermine are prescription medications that can help with weight loss, and they work through different mechanisms. Since both drugs can produce weight loss, you might wonder if you could combine the two to give your weight loss efforts an extra boost. Unfortunately, there’s no clear research about whether combining phentermine and semaglutide is effective or safe for weight loss. Read on as we explore the potential benefits and risks of combining these medications for weight loss.

Phentermine is not listed on the semaglutide label as a potential drug interaction. However, the phentermine label does mention caution when combining phentermine with insulin and oral hypoglycemic medications. Semaglutide is used for the treatment of type 2 diabetes with the goal of lowering blood sugar, so caution should be used when combining the medications. The phentermine drug label also recommends combining phentermine with other medications that can cause weight loss.

Ultimately, the best person to ask this question is your healthcare provider. You may or may not be a good fit for one or both drugs based on your personal medical history, current health conditions, and other medications you are taking. 

People taking semaglutide may lose nearly 11% of their body weight over a period of six months. According to the FDA drug label for phentermine, the amount of weight loss associated with the use of phentermine varies from trial to trial but it is noted the rate of weight loss is greatest in the first weeks of therapy and decreases in succeeding weeks. Because both semaglutide and phentermine lead to weight loss, it’s possible taking them together may provide certain weight loss benefits, although no research has been done to suggest it.

Independent studies of semaglutide and phentermine have shown that either drug can help reduce body weight, appetite, and cravings, but no studies to date have observed the effects of combining phentermine and semaglutide as a weight loss method. It’s important to talk to your healthcare provider if you are considering taking these medications together, because the potential risks of this combination are unknown. On the phentermine drug label, it’s actually recommended against taking the medication alongside any other medication that can cause weight loss.

There could be risks to taking semaglutide and phentermine together, since combining these medications for weight loss has not been studied.

Side effects

Both semaglutide and phentermine cause side effects, some of which can be serious. Combining medications may increase risks, particularly of hypoglycemia in patients with type 2 diabetes as this is specifically mentioned in the FDA drug label of phentermine. 

Both medications can cause side effects like diarrhea, constipation, dizziness, and headache. Common side effects are listed below.

Serious side effects of semaglutide may include acute pancreatitis, kidney or gallbladder problems, an allergic reaction to the medication, or vision changes (in people with type 2 diabetes). Serious side effects of phentermine may include primary pulmonary hypertension, regurgitant cardiac valvular disease, and abuse or dependence. As with all medications, it is important to discuss the potential risks and benefits with a healthcare provider.

Drug interactions

Both medications can interact with other drugs. People taking insulin may need to adjust their dosage of insulin when taking semaglutide or phentermine, as either drug may increase the risk of hypoglycemia (low blood sugar). Phentermine should not be mixed with alcohol, monoamine oxidase inhibitors, adrenergic neuron-blocking drugs, or other weight loss stimulants like bupropion/naltrexone.

Also, because semaglutide slows down digestion, it’s possible that it may affect the absorption of oral medications including phentermine.  

Risk groups

Taking either semaglutide or phentermine can be risky for people with certain health conditions. For example, semaglutide should not be used by pregnant people, both men and women planning to conceive in the near future, or anyone with a personal or family history of certain thyroid cancers, including medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia syndrome type 2 (MEN 2). Additionally, people with type 2 diabetes, and kidney or gallbladder issues may need extra monitoring when taking semaglutide. 

Phentermine should not be used by people who are pregnant or nursing, recently started taking monoamine oxidase inhibitors, or who have:

• A history of heart problems

• Hyperthyroidism

• Glaucoma

• Agitation

• A history of drug abuse

Semaglutide is the active ingredient in the brand name drugs Ozempic, Wegovy, and Rybelsus. Ozempic and Wegovy are both once-weekly injectable medications, while Rybelsus is a daily oral medication. Each medication contains different doses of semaglutide and is intended as a long-term medication, to be used in combination with diet and exercise. 

Different forms of semaglutide are FDA-approved to treat different conditions. Ozempic and Rybelsus are both approved to treat type 2 diabetes by lowering blood sugar levels. Ozempic is also approved to lower the risk of experiencing heart attack, stroke, or death in people with both type 2 diabetes and heart disease. Because they can lead to weight loss, health providers may prescribe Ozempic or Rybelsus for weight loss, but these prescriptions would be considered off-label since the medications are not FDA-approved specifically for weight loss. 

Wegovy is the only medication containing semaglutide that is FDA-approved specifically for weight loss. It may be prescribed to adults with obesity (having a body mass index, or BMI, of 30 or higher) or with overweight (a BMI of 27 or higher) and a weight-related health condition such as high blood pressure or cholesterol. 

In one clinical trial, people taking the 2.4 mg dosage of semaglutide lost approximately 9.6% of their body weight after 28 weeks, compared with approximately 7% for those taking the 1 mg dose of semaglutide. Within two years, people taking the 2.4 mg dosage of semaglutide lose 15.2% of their body weight, on average.

The most common side effects of semaglutide are gastrointestinal in nature, including nausea, diarrhea, and vomiting. Thankfully, these are most common in the beginning weeks of treatment, and tend to subside with time as your body gets used to the medication. 

Unlike semaglutide, phentermine is intended to be a short-term medication, in part because people develop a tolerance to it. It is an FDA-approved appetite suppressant that should be used with diet and exercise by people with obesity (BMI of 30 or higher) or overweight (BMI of 27 or higher) with a weight-related health condition. Phentermine may be sold under the brand names Adipex-P, Lomaira, and Suprenza. You can also find it in the brand name drug Qsymia, which combines phentermine and topiramate. 

While the FDA recommends limiting phentermine treatment to three months, some people have more success losing weight when they take phentermine for up to six months, especially in people for whom phentermine didn’t work during the first three months. For 42% of people who did not respond within the three-month time period, it took a bit longer — up to six months — to lose at least 5% of their body weight with phentermine. It is up to your healthcare provider whether taking phentermine for a longer period of time could be effective or safe for you. Overall, it seems like different people respond to the medication differently which causes some differences between available studies of the medication.

Phentermine’s side effects vary but can include dry mouth, headache, sweating, and unpleasant taste. Side effects can be more common with higher doses of phentermine. 

Generally, phentermine is considered a short-term medication for weight loss, while semaglutide is intended to be used on a longer-term basis. While no study has compared the two drugs directly, Wegovy (the version of semaglutide that is FDA-approved for weight loss) typically produces more weight loss. 

On average, people taking Wegovy lose an average of 15% of their body weight in 68 weeks. People may lose as much as 6% of their body weight by three months, and nearly 11% by six months. With phentermine, on the other hand, some people develop a tolerance, so weight loss can be more pronounced in the beginning and then level off after a few months. About half of people taking phentermine lose at least 5% of their body weight within three months. By six months, roughly 80% have reached that 5% milestone. 

So if you’re trying to lose weight, is phentermine or semaglutide the better option for you? The answer depends on a number of factors, as the amount of weight loss can vary widely depending on your personal response to the medication, existing health conditions, adherence to a diet and exercise routine, and the dosage you’re taking. 

Phentermine is technically approved for weight loss for up to 12 weeks, though some health providers may prescribe it for longer depending on clinical judgment. On the other hand, semaglutide should be taken long-term for weight loss and management. Your decision may also depend on how much weight you have to lose. People taking 2.4 mg of semaglutide may lose anywhere between 9.6%-17.4% of their body weight within about 68 weeks while those taking Qsymia (a combination of phentermine/topiramate) may lose 5% to 10.6% within a year. People taking higher doses of the medications tend to lose more weight (but they also may experience more side effects). 

Speaking of side effects, you may find the potential side effects of one medication to be more tolerable than the other. Nausea, diarrhea, and vomiting are more common with semaglutide, while dry mouth, headache, and sweating are more common with phentermine. The two weight loss medications offer different forms of administration, as well. Phentermine is a daily oral tablet that should be taken in the morning, with or without food, while semaglutide is either injected under the skin on a weekly basis, at any time of day, or as an oral tablet.

Finally, cost and availability may be considerations. Phentermine is widely available and much cheaper than semaglutide. Wegovy costs upwards of $1,000 for a monthly supply without insurance, and is often experiencing a shortage in one or more dosage amounts (although compounded semaglutide is typically cheaper and more available). Phentermine, on the other hand, usually costs less than $20 for a month’s supply. 

There’s a lot to consider when choosing a medication for weight loss. Talk about your options with your healthcare provider. And whichever medication you choose, taking it regularly as prescribed, and combining it with diet and exercise, is the best path to success.

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Current version

March 29, 2024

Written by

Amelia Willson

Fact checked by

Raagini Yedidi, MD

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About the medical reviewer

Raagini Yedidi, MD

Raagini Yedidi, MD, is an internal medicine resident and medical reviewer for Ro.