ItalianoThe medical field has increasingly focused on pharmaceutical options for addressing obesity. Prior to 2012, the Food and Drug Administration (FDA) had approved only a small handful of drugs for weight reduction. Among the most utilized were phentermine—sold under names like Lomaira and Adipex-P—and orlistat, known commercially as Xenical and Alli.
The introduction of GLP-1 receptor agonists (Glucagon-like peptide-1), such as Wegovy and Ozempic, revolutionized the market and sparked significant public interest. A 2022 study published in Frontiers in Cardiovascular Medicine noted that web searches and prescription rates for these medications have surged in parallel.
As the landscape of available therapies expands, a common question arises: which is the most powerful weight loss drug? The answer isn’t straightforward, as efficacy varies by individual, and the marketplace continues to evolve rapidly. Thus, staying informed about the options, their strengths, and limitations is essential.
Eligibility Guidelines for Weight Loss Medication
Evaluating whether someone qualifies for pharmacological weight loss treatment typically starts with assessing their Body Mass Index (BMI). In general, medications are prescribed to individuals with a BMI of 30 or above, or those with a BMI of at least 27 who also suffer from health issues linked to excess weight.
In November 2023, the FDA approved Zepbound for adult patients with a BMI of 30 or more. However, choosing the right medication involves a broader discussion between physician and patient, factoring in overall health, current prescriptions, family history, potential side effects, and cost.
While some drugs are strictly for adult use, semaglutide, liraglutide, and orlistat have received FDA clearance for patients 12 years and older. Notably, none of these medications are suitable for pregnant individuals.
Available Pharmaceutical Options for Weight Loss
Both longstanding and newly developed drugs are now part of the treatment arsenal for obesity. Key medications currently prescribed include:
Semaglutide (Wegovy, Ozempic)
Wegovy, a GLP-1 receptor agonist, is an injectable drug approved by the FDA in 2021 for treating obesity in adults and adolescents 12 and up. It is typically prescribed to adults with a BMI ≥30 or those with a BMI ≥27 plus a related health condition. Pediatric eligibility is defined by being at or above the 95th percentile in BMI for age and sex. The dosage increases gradually over 16 to 20 weeks to a 2.4 mg maintenance level, which helps mitigate side effects like nausea, fatigue, dizziness, and headaches.
Ozempic, while chemically identical, is approved for managing type 2 diabetes.
Tirzepatide (Zepbound, Mounjaro)
Initially introduced for diabetes treatment under the name Mounjaro, tirzepatide is now marketed as Zepbound for obesity management in adults with BMI ≥30. This dual-action agent targets both GLP-1 and GIP receptors, helping to reduce hunger and food intake. Like semaglutide, it is administered by injection and should be used alongside lifestyle changes such as a healthy diet and exercise.
Liraglutide (Saxenda)
Saxenda is a daily injectable medication that influences gut-derived hormones to increase feelings of fullness and reduce hunger. Patients typically start with a 0.6 mg dose, gradually reaching up to 3 mg daily. With higher doses, many individuals can shed 5–10% of their body weight. Side effects include gastrointestinal discomfort, fatigue, and dizziness. This medication is unsuitable for people with a history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.
Phentermine (Adipex, Suprenza)
Phentermine, the oldest FDA-approved weight loss drug, was initially intended for short-term use but is now incorporated into long-term treatment strategies. Average weight reduction can be around 5%. It’s commonly prescribed in 15 mg or 30 mg formulations. Side effects may include insomnia, elevated blood pressure, irregular heartbeat, and nervous system stimulation. Phentermine should not be combined with MAO inhibitors, alcohol, or certain other medications.
Phentermine-Topiramate (Qsymia)
Combining phentermine with topiramate enhances the appetite-suppressing effects of each component. It’s a good option for patients with both obesity and migraines. Average weight loss ranges between 5–10%. If patients do not achieve at least a 5% reduction after 12 weeks at the maximum dose, tapering off the medication is advised. Daily doses vary from 3.75 mg/23 mg to 15 mg/92 mg. Common side effects include taste alteration, constipation, and dry mouth.
Naltrexone-Bupropion (Contrave)
This combination of an opioid receptor blocker and an antidepressant targets the brain’s reward system to reduce cravings and hunger. Weight loss typically ranges from 5–10%. Dosing begins with one 8/90 mg tablet daily, building up to four tablets per day. Side effects can include insomnia, nausea, dizziness, and gastrointestinal issues. This medication is contraindicated in patients taking opioids or those with seizure disorders.
Setmelanotide (Imcivree)
Designed for a niche group of patients, setmelanotide is used in children and adults (6 years and older) with obesity caused by rare genetic disorders. It works by stimulating the melanocortin-4 receptor. Eligibility requires genetic confirmation of pathogenic variants in POMC, PCSK1, or LEPR genes.
Orlistat (Xenical, Alli)
Orlistat is a lipase inhibitor that limits fat absorption from food by blocking digestive enzymes. The undigested fat is eliminated through bowel movements. Prescription-strength capsules (120 mg) are taken with meals, while a 60 mg OTC version is also available. It’s typically used alongside a calorie-controlled diet. Side effects are mostly digestive, such as oily stools or increased bowel urgency.
Hydrogel (Plenity)
Although not technically a medication, Plenity is FDA-approved as a weight loss device for individuals with a BMI between 24 and 40. It comes in capsule form and releases a water-absorbing hydrogel that expands in the stomach to promote satiety. Real-world use suggests an average weight loss of 9%.
Emerging Therapies for Weight Loss
Given the rising demand and prevalence of obesity, pharmaceutical companies are investing heavily in next-generation treatments.
Eli Lilly is developing orforglipron, an oral GLP-1 agent. Retatrutide, another injectable in development, acts on GLP-1, GIP, and glucagon pathways. Pfizer’s pipeline includes two oral GLP-1 candidates. Meanwhile, Amgen is exploring a unique compound that functions as a GLP-1 receptor agonist and a GIP receptor antagonist.
Researchers are also investigating hormones like peptide YY to discover new mechanisms of appetite regulation. According to Dr. Robert Kushner from Northwestern University, this shift marks a more endocrine-centered approach to obesity—providing more targeted and diverse treatment options.
Monoclonal antibodies, widely studied for many conditions, are being tested in obesity treatment too. For instance, bimagrumab is being researched for its ability to build muscle while reducing fat.
This wave of innovation may enable doctors to tailor treatment more precisely than ever before.
FAQs About Weight Loss Drugs
How effective are these medications?
FDA-approved anti-obesity treatments target physiological mechanisms and show the best results when combined with lifestyle changes. Outcomes vary based on the drug used, patient health, and individual response.
Some drugs have been removed from the market due to either limited effectiveness or safety issues.
Which drug works best for weight loss?
Semaglutide has demonstrated impressive outcomes in clinical trials. One 2022 study showed nearly 11% weight loss in six months. Another, published in the New England Journal of Medicine, reported average weight loss close to 15%. However, drawbacks include its high cost, side effects, and the need for long-term treatment.
Patients should collaborate closely with their physicians to determine the most suitable approach for their unique circumstances.
What medications are endorsed by expert bodies?
In 2022, the American Gastroenterological Association recommended semaglutide, liraglutide, phentermine-topiramate ER, and naltrexone-bupropion ER as first-line treatments for patients unresponsive to lifestyle changes. They also mentioned phentermine and diethylpropion—though this guidance predated Zepbound’s approval.
How do these drugs help with weight loss?
These medications primarily modulate hormone activity in the brain and digestive tract to curb hunger and boost feelings of fullness. While some are injectable, others come in pill form. Notably, oral and injectable GLP-1s show similar efficacy.
Can certain medications lead to weight gain?
Yes, numerous drugs can promote weight gain, including:
- Certain beta-blockers and calcium channel blockers
- Insulin and other diabetes therapies like sulfonylureas
- Hormonal treatments such as corticosteroids
- Anti-seizure medications like gabapentin and valproate
- Some antidepressants, mood stabilizers, antipsychotics, and migraine drugs
Should weight loss drugs be combined with other treatments?
Yes. These drugs are most effective when integrated into a broader plan that includes diet, physical activity, and possibly surgery. They can reduce cravings and maintain metabolic balance during weight loss efforts.
How long do patients typically take these medications?
Duration depends on the medication. Some are short-term (up to 12 weeks), while others are designed for long-term use. Examples of the latter include orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide. For chronic disease management, ongoing treatment may be necessary.
How has the medication landscape evolved?
While GLP-1 agonists are currently prominent, obesity treatment has a rich history of innovation. New medications increasingly target specific hunger signals, metabolic processes, and receptors to enhance safety and effectiveness.
What about cost differences?
Older medications tend to be more affordable and may have generic forms. In contrast, newer GLP-1 agents like Wegovy are expensive—estimated around $13,600 annually. Some, like phentermine, can cost as little as $10. Insurance coverage is a major factor in access, and Medicare currently does not cover these drugs.
Do they help prevent regaining weight?
Yes, anti-obesity medications may help mitigate the body’s tendency to regain weight after initial loss. They can maintain hormonal balance and metabolic rate, especially when continued during maintenance phases.
How do OTC and prescription drugs compare?
Alli (orlistat) is the only FDA-approved over-the-counter weight loss drug. Other OTC products are dietary supplements and not subject to the same regulations or safety standards. Prescription drugs offer physician oversight and dose adjustments.
What’s the relationship between antidepressants and weight?
Most antidepressants are either weight-neutral or associated with weight gain. However, bupropion (Wellbutrin) is an exception, as it often contributes to weight loss. Effects vary by individual and drug class—some SSRIs like paroxetine are more likely to increase weight, while others like fluoxetine may not.
Which medications specifically reduce appetite?
Appetite suppression is a primary effect of drugs such as tirzepatide (Zepbound), liraglutide (Saxenda), naltrexone-bupropion (Contrave), and phentermine-topiramate (Qsymia). Additionally, stimulant-based medications like phentermine, benzphetamine, and diethylpropion also diminish appetite through different pathways.