Here’s How GLP-1’s Compare To Other Weight Loss Medications
The demand for prescription weight loss medications has surged in recent years, driven by both the obesity epidemic and advances in pharmacology. According to the CDC, over 42% of U.S. adults are considered obese, and with traditional weight loss strategies like diet and exercise proving insufficient for many, physicians are increasingly turning to medication as an adjunct treatment. Among the most well-known today are GLP-1 receptor agonists, medications like semaglutide and tirzepatide that have been shown to help patients lose a significant percentage of body weight. However, they are not the only options available. This article compares GLP-1 medications with several other commonly prescribed weight loss drugs, examining how they work, how effective they are, and who might benefit most from each.
What Are GLP-1 Medications?
GLP-1 receptor agonists are a class of medications originally developed to manage type 2 diabetes. These drugs mimic glucagon-like peptide-1, a naturally occurring hormone that regulates appetite and blood sugar levels. By slowing gastric emptying and signaling fullness to the brain, GLP-1s help people eat less and feel satisfied with smaller meals.
Semaglutide, marketed under brand names such as Ozempic (for type 2 diabetes) and Wegovy (for chronic weight management), has been shown in clinical trials to help patients lose approximately 15% of their body weight over 68 weeks. Tirzepatide, sold as Mounjaro and Zepbound, works similarly but also targets another hormone, GIP, which may further enhance weight loss. In studies, tirzepatide users lost up to 22.5% of their body weight, setting a new benchmark among weight loss medications.
Common side effects include nausea, vomiting, diarrhea, and constipation, particularly in the early stages of treatment. These symptoms tend to lessen over time. Less frequent but more serious risks include pancreatitis, gallbladder issues, and in rare cases, thyroid tumors.
Other Popular Weight Loss Medications
Phentermine
Phentermine is one of the oldest weight loss drugs still in use. Approved for short-term treatment of obesity, it works by stimulating the central nervous system to suppress appetite, like how amphetamines affect the brain. Typically prescribed for no more than 12 weeks, phentermine can result in rapid initial weight loss, which can be motivating for some patients.
However, because of its stimulant properties, phentermine is associated with side effects such as increased heart rate, elevated blood pressure, anxiety, insomnia, and dependency risks. It is not recommended for individuals with cardiovascular conditions or a history of substance abuse.
Orlistat (Alli®, Xenical®)
Orlistat takes a completely different approach from appetite suppressants. Instead of acting on the brain, it works in the digestive tract to block the absorption of about 25–30% of dietary fat. The unabsorbed fat is then excreted in the stool, which can lead to side effects such as oily stools, flatulence, and fecal urgency, especially when consuming high-fat meals.
Orlistat is available in both prescription strength (Xenical) and a lower-dose over-the-counter version (Alli). Because it is not a stimulant, it may be suitable for people who cannot take medications like phentermine. However, weight loss results are generally modest, averaging 5–10 pounds over several months.
Contrave® (Bupropion/Naltrexone)
Contrave is a combination drug that targets the brain’s hunger and reward systems. Bupropion is an antidepressant also used for smoking cessation, while naltrexone is used to treat opioid and alcohol dependence. Together, these medications help reduce food cravings and improve appetite control.
Contrave is especially useful for patients who experience emotional or reward-driven eating. However, it does carry risks. Side effects can include nausea, constipation, dizziness, and an increased risk of mood changes or suicidal thoughts, particularly in individuals with a history of depression or psychiatric illness. It is not recommended for those with seizure disorders or uncontrolled hypertension.
Qsymia® (Phentermine/Topiramate)
Qsymia combines low-dose phentermine with topiramate, a medication originally used to treat epilepsy and migraines. The two drugs work together to suppress appetite and enhance feelings of fullness, leading to effective weight loss; often 10 to 15% of total body weight.
While Qsymia is one of the most effective non-GLP-1 medications, it does come with potential drawbacks. Common side effects include dry mouth, constipation, and a tingling sensation in the hands or feet. More concerning are cognitive issues such as memory problems or difficulty concentrating. The drug also poses a significant risk of birth defects and must not be used during pregnancy, making it unsuitable for women who are or may become pregnant.
Key Differences: GLP-1s vs. Other Weight Loss Medications
The differences between GLP-1s and other weight loss drugs lie primarily in how they work, how effective they are, how they are taken, and how long they can be used.
Mechanism of action is a major differentiator. GLP-1s mimic natural hormones involved in appetite and glucose regulation, while older medications tend to rely on central nervous system stimulation (like phentermine and Qsymia) or digestive fat-blocking (as with orlistat).
In terms of effectiveness, GLP-1s outperform most other options. Clinical trials consistently show weight loss of 15–20% or more with GLP-1s, compared to 5–10% with medications like Contrave, orlistat, and phentermine. Qsymia comes closest but still falls slightly short of GLP-1 results.
Duration of use also varies. Phentermine is approved for short-term use only, while GLP-1s, Contrave, Qsymia, and orlistat are all approved for long-term treatment. Since obesity is a chronic condition, this distinction is crucial for lasting results.
When comparing side effects, GLP-1s tend to produce gastrointestinal symptoms that taper off with time. Other medications may involve cardiovascular risks (phentermine), neurological or cognitive side effects (Qsymia), or mood-related concerns (Contrave). Orlistat’s gastrointestinal effects are often the most disruptive to daily life.
Administration method is another key difference. GLP-1s are typically injected once a week, although oral versions are now in development. Other medications are taken as daily pills, which may be more appealing to needle-averse patients.
Lastly, cost and insurance coverage can be a barrier. GLP-1s are among the most expensive weight loss medications, with monthly costs often exceeding $1,000. Medical insurance does cover glp-1’s in some cases, however many plans limit coverage to patients with diabetes or severe obesity. Older weight loss medications like phentermine and orlistat are far more affordable and widely covered.
Who Might Be a Good Candidate for Each Type?
GLP-1 medications are best suited for individuals with a BMI of 30 or higher, or 27 and above with weight-related comorbidities like type 2 diabetes or high blood pressure. They are ideal for patients looking for gradual, sustained weight loss and who can commit to weekly injections and regular monitoring. Here is a dedicated blog post on glp-1 weight loss candidacy.
Patients looking for more rapid initial weight loss may benefit from short-term use of phentermine, though it should only be used under close supervision. Orlistat is a better fit for people looking for a non-stimulant, over-the-counter option, though they must be willing to follow a low-fat diet to minimize gastrointestinal side effects.
Contrave is often prescribed to those dealing with emotional eating or co-existing mental health issues, although it’s not suitable for patients with seizure risk or certain psychiatric conditions. Qsymia is a good option for those needing substantial weight loss but is contraindicated in pregnancy and may not be appropriate for individuals sensitive to cognitive side effects.
The Role of Lifestyle and Combination Therapies
No matter the medication, weight loss success is greatly improved when drugs are combined with lifestyle changes. A balanced, calorie-conscious diet, regular exercise, and behavioral counseling can enhance outcomes and support long-term success. While some medications may be combined in rare cases, this should only be done under strict medical guidance.
Supervision by a qualified healthcare provider is critical to both the success of the weight loss journey and the safety of the patient. Such supervision is important, not just for prescribing and monitoring medications, but for providing support, adjusting treatment plans, and helping patients set realistic expectations.
Today’s weight loss medications offer more personalized and effective options than ever before. GLP-1 receptor agonists have redefined what’s possible in terms of sustainable weight loss, but they are not the only choice. Depending on your health profile, goals, and preferences, other medications like phentermine, orlistat, Contrave, or Qsymia may also be appropriate.
Ultimately, the best approach involves a thoughtful discussion with your healthcare provider. With the right plan in place, including medication, lifestyle changes, and ongoing support, long-term weight loss is not only possible but achievable.
Dr. Gordon is Board Certified by the American Board of Dermatology and is a member of the American Society of Dermatologic Surgery (ASDS), the American Academy of Dermatology, the Dermatology Foundation, the Texas Medical Association and the Travis County Medical Society. Currently, Dr. Gordon oversees our South Austin location.
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