Obesity is a multifaceted and chronic condition characterized by excessive fat accumulation, posing significant risks to overall health and is associated with various metabolic and cardiovascular complications. People who live with obesity face increased health risks such as greater chances of developing hypertension, heart disease, and type 2 diabetes. That’s why medications, in combination with lifestyle changes, have become so popular for treating obesity and helping with weight loss. As more people look for medical support to reach and maintain a healthy weight, interest in prescription weight-loss treatments has increased. Two medications that people often turn to for weight loss are phentermine and Wegovy®, with some also using Wegovy®’s sister medication Ozempic®, which is FDA-approved for diabetes and contains the same active ingredient, semaglutide. Semaglutide and phentermine are both popular weight loss drugs, but they are very different. Both semaglutide and phentermine medications remain central to today’s conversation about medical weight loss.
This article aims to provide a detailed comparison of phentermine and semaglutide, two medications commonly prescribed for weight loss. It will explore their mechanisms of action, efficacy, potential side effects, and other key factors to help individuals make informed decisions about their weight loss journey.
Understanding Obesity
Obesity is recognized as a multifaceted and long-term condition marked by the abnormal accumulation of body fat, which can negatively impact overall health. Its development is influenced by a mix of genetic predispositions, environmental exposures, behavioral patterns, and metabolic factors. Obesity occurs when there is an imbalance between the calories consumed and the energy expended, leading to an excessive buildup of fat in the body. It is commonly evaluated using the body mass index (BMI), which is calculated by dividing a person’s weight in kilograms by the square of their height in meters. Excessive weight gain has been escalating rapidly worldwide, with over one-third of the global population now classified as either overweight or obese.
Weight classifications based on BMI are as follows: individuals with a BMI over 25 kg/m² are categorized as overweight, while those exceeding 30 kg/m² are classified as obese. A BMI between 18.5 and 25 kg/m² is considered normal, whereas a BMI below 18.5 kg/m² indicates underweight status. According to WHO guidelines, individuals with a BMI below 18.5 kg/m² are classified as underweight, while those within the 18.5-24.9 range fall under the normal weight category. A BMI of 25-29.9 is considered overweight, whereas obesity is further categorized into the following three classes based on severity: class I obesity (BMI: 30-34.9 kg/m²), class II obesity (BMI: 35-39.9 kg/m²), and class III obesity (BMI: ≥40 kg/m²).
Obesity can result from a variety of mechanisms. It has been attributed to an imbalance where energy intake significantly exceeds the energy expended by the body. This imbalance causes fat cells to enlarge abnormally, disrupting the nutrient signaling pathways that contribute to obesity. However, recent research suggests that the source and quality of nutrients in a diet are more critical than their quantity for effective weight management and disease prevention. Additionally, genetic predisposition plays a significant role in influencing an individual’s susceptibility to weight gain. Factors such as the accumulation of lipid metabolites, inflammatory processes, and dysfunction in hypothalamic neurons may also contribute to obesity, potentially explaining the biological mechanisms that favor the maintenance of excessive body fat.
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Phentermine: An Appetite Suppressant
Phentermine is a sympathomimetic amine that stimulates the central nervous system. The FDA first approved it as an appetite suppressant in 1959. It’s sold under the brand names Adipex-P, Lomaira, and Suprenza and is also sold in combination with a drug called topiramate in a medication called Qsymia. Adipex-P (phentermine hydrochloride) is a prescription medication used as a short-term adjunct to weight loss in patients with obesity. As a central nervous stimulant and “anorectic” (hunger suppressing) medication, phentermine works as an appetite suppressant by stimulating the central nervous system, which increases heart rate and blood pressure while reducing hunger. It’s unclear exactly how phentermine reduces appetite, but it may increase neurotransmitter levels in your brain.
Phentermine is typically prescribed alongside a reduced-calorie diet and exercise regimen to enhance weight loss efforts. It is considered a controlled substance that can be addictive and carries the risk of withdrawal symptoms and potential side effects such as a racing or irregular heartbeat. This medication is not recommended for use in people with glaucoma, hyperthyroidism, or a history of cardiovascular disease.
Dosage and Administration
Phentermine has two primary formulations. The first is a 37.5 mg tablet, and the second is a 30 mg extended-release capsule. Phentermine is usually taken once daily in the morning, either before breakfast or a couple of hours afterward, depending on the prescription. Common doses range from 15 mg to 37.5 mg per day. People start at the lowest dose to help the body adjust and then gradually increase as needed.
Efficacy of Phentermine
Studies show that, when paired with healthy eating and regular activity, people taking phentermine lose an average of 5% of their starting weight over 12 weeks. Many people in practice have lost their desired amount using phentermine, ranging from 20 - 150 pounds or more.
Side Effects of Phentermine
Common side effects of phentermine include increased heart rate, dry mouth, insomnia, and nervousness. More serious adverse effects can be life-threatening, and symptoms should not be ignored. They include - increased blood pressure, tachycardia (heart rate over 100 beats per minute), pulmonary hypertension, disease of the heart valves, or even events related to ischemia (loss of blood flow) to the heart or other organs. You may experience unpleasant side effects from phentermine, including:
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- Insomnia
- Headache
- Fast or irregular heartbeat
- Dry mouth
- Mood changes
- Hypertension
- Heart failure
- Hallucinations
- Reduced sex drive
Additionally, people who take high doses of phentermine may experience withdrawal symptoms. This medication may also impair your ability to perform potentially hazardous tasks such as using heavy machinery or driving a car.
Precautions and Contraindications
It is important to note that Adipex-P is intended for short-term use due to the potential for dependence and other adverse effects. Phentermine is contraindicated in individuals with:
- History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension)
- During or within 14 days following the administration of monoamine oxidase inhibitors
- Hyperthyroidism
- Glaucoma
- Agitated states
- History of drug abuse
- Pregnancy
- Nursing
- Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines
Semaglutide: A GLP-1 Receptor Agonist
Semaglutide is the active ingredient in the brand-name medication Wegovy®. Wegovy® (semaglutide) is an injectable medication approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It’s commonly sold under the brand names Wegovy and Ozempic in injectable form and Rybelsus in pill form. Although the FDA approved semaglutide for weight loss in 2021, this medication’s use in treating type 2 diabetes and heart disease dates back to Ozempic’s 2017 approval for reducing the risk of heart attack, stroke, or death in people with type 2 diabetes.
It works by mimicking the hormone glucagon-like peptide-1 (GLP-1), which regulates appetite and food intake, leading to reduced calorie consumption and significant weight loss. It works by mimicking the GLP-1 hormone, causing your body to produce more insulin, lowering your blood sugar levels, and signaling fullness to your brain.
Wegovy® is administered once weekly and is intended to be used in conjunction with a reduced-calorie diet and increased physical activity. It’s designed for long-term use, but people who take semaglutide may experience weight gain if they stop taking the medication. It can affect your body’s response to insulin and insulin-releasing medications, so your doctor may need to adjust your dosages of these medications to reduce the risk of hypoglycemia (low blood sugar). Injectable versions of semaglutide may also affect the absorption of other medications taken orally, including over-the-counter aspirin and allergy medications.
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Dosage and Administration
Semaglutide is a once-weekly injection that is either administered via an autoinjector pen or drawn up into a syringe and injected. Wegovy® and Ozempic® are taken as once-weekly injections that come in prefilled pens and are given under the skin of the upper arm, thigh, or stomach. The dosing schedule begins with a small introductory dosage of 0.25 mg and is increased slowly until a therapeutic dosage (a dose which provides good hunger suppression, minimal side effects, and consistent weight loss) is reached or the highest FDA-approved dose, 2.4 mg, is reached.
Efficacy of Semaglutide
In clinical studies, people lost an average of 15% of their starting weight over 68 weeks at the highest dose of Wegovy (2.4 mg), with some losing even more. Semaglutide is typically associated with more weight loss than phentermine, but results still depend heavily on eating habits and physical activity. Four trials were completed on the effectiveness of semaglutide. The average weight loss percentage was -13.5% of starting weight among 2,117 participants. For example, in the average person weighing 200 lbs. at starting, this would be a 26 lb. 1% of participants lost more than 15% of their starting weight. For example, in a person weighing 200 lbs. at starting, this would be a 30 lb. In practice, many patients routinely lose 20% or more of their starting weight using semaglutide.
Side Effects of Semaglutide
Common side effects of Wegovy® include nausea, diarrhea, vomiting, and constipation. Semaglutide acts on the digestive and hormonal systems and is more likely to cause nausea, vomiting, diarrhea, or constipation, particularly in the early stages of treatment or when the dose is increased. Possible side effects of semaglutide include:
- Nausea and vomiting
- Constipation or diarrhea
- Headache
- Abdominal pain
- Fatigue
- Hypoglycemia
Precautions and Contraindications
It should be used with caution in patients with a history of pancreatitis and is not recommended for use in pregnant or breastfeeding individuals. Semaglutide is contraindicated in patients with:
- Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2
- Known hypersensitivity to semaglutide or any of the excipients in Wegovy®
Boxed Warning
Semaglutide carries a boxed warning regarding the risk of thyroid C-cell tumors. In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.
Comparing Phentermine and Semaglutide
Semaglutide and phentermine can both help with weight loss, but how they work inside the body differs. The two medications have similar goals but work in different ways. Here’s a breakdown of the key differences:
- Mechanism of Action: Phentermine is a stimulant that boosts brain chemicals, like norepinephrine, to suppress hunger signals. Semaglutide is a GLP-1 receptor agonist that slows digestion, reduces appetite, and regulates blood sugar.
- Administration: Phentermine is taken as a daily oral pill. Wegovy® and Ozempic® are taken as once-weekly self-injections.
- FDA Approval and Uses: Phentermine is FDA-approved for short-term weight loss (about 12 weeks); longer use is off-label. Wegovy® is FDA-approved for weight loss and preventing heart disease. Ozempic® can be prescribed for off-label weight loss.
- Duration of Treatment: Phentermine is intended for short-term weight loss, with FDA approval for about 12 weeks of use. Wegovy® and Ozempic® are meant for longer-term treatment, with most doctors prescribing semaglutide medications for a minimum of 6 to 12 months.
- Weight Loss Results: Semaglutide is typically associated with more weight loss than phentermine, but results still depend heavily on eating habits and physical activity. Phentermine can help kickstart weight loss in a shorter window, but Wegovy® typically leads to more substantial reductions over time.
- Side Effects: Phentermine, which stimulates the central nervous system, can lead to cardiovascular and nervous system effects such as higher blood pressure, a faster heart rate, restlessness, and trouble sleeping. Semaglutide acts on the digestive and hormonal systems and is more likely to cause nausea, vomiting, diarrhea, or constipation, particularly in the early stages of treatment or when the dose is increased.
- Cost: Phentermine is generally budget-friendly, with a typical monthly cost of about $37 to $41 for generic tablets or capsules. Wegovy® averages around $1,350 per month without insurance, while Ozempic® has a list price of $998.
- Availability: Wegovy® and Ozempic® can be prescribed through telehealth.
Combining Semaglutide and Phentermine
Semaglutide and phentermine can generally be used together since they do not interact. Some patients opt for dual therapy at some point during their treatment. However, it’s important to check with your doctor about your specific health needs and whether these drugs are appropriate for your care plan. Both semaglutide and phentermine can be used in combination with diet, exercise, and behavioral changes to help with weight loss.
Switching Between Medications
You can switch between semaglutide medications and phentermine, but you should only do so under medical supervision. Moving from semaglutide to phentermine means going from a long-acting weekly injection to a short-term daily pill. Phentermine can help reduce hunger, but it doesn’t directly influence digestion or appetite signals the way Wegovy® does, so you may notice a difference in how full you feel between meals. Semaglutide generally offers steadier appetite control and may support greater weight loss over time.
Maintaining Weight Loss After Discontinuation
Phentermine treatment is usually limited to about 12 weeks. Semaglutide doesn’t permanently change how your body works, so stopping it can lead to some weight regain. Still, that doesn’t mean weight will automatically return. Having healthy habits around eating and movement while on the medication also makes a big difference.
Other Weight Loss Medications
If neither phentermine nor Wegovy® feels like the right fit, whether because of cost, side effects, or lifestyle preferences, there are other prescription options to explore. Other pharmacological agents include liraglutide, orlistat, and emerging agents like setmelanotide, amycretin, retatrutide, cagrilintide, and cotadutide.
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