The landscape of obesity treatment has changed dramatically, with pharmacological interventions gaining significant traction. Prior to 2012, options were limited, primarily to phentermine (Lomaira, Adipex-P) and orlistat (Xenical, Alli). However, the emergence of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as Wegovy and Ozempic, has captured widespread attention, reflected in increasing online searches and prescriptions, as noted in a 2022 study in Frontiers in Cardiovascular Medicine.
With this expanded array of weight loss medications, a common question arises: What Is The Strongest Weight Loss Prescription Pill? The answer, however, is nuanced. Determining the most suitable medication is not straightforward and varies from person to person. Furthermore, the market is dynamic, necessitating continuous updates on available choices and their respective advantages and disadvantages.
Qualifying for Weight Loss Medication: Key Criteria
The initial step in considering weight loss medications is evaluating Body Mass Index (BMI). Generally, these medications are prescribed for individuals with a BMI of 30 or higher, or a BMI of 27 or greater if accompanied by weight-related health issues.
Zepbound, recently approved in November 2023 for adults with a BMI of 30 or more, exemplifies this. For each patient, a thorough discussion between doctor and patient is crucial, encompassing health status, existing medications, and family medical history. Cost and potential side effects are also integral factors in the decision-making process.
While some weight loss medications are restricted to adult use, semaglutide, liraglutide, and orlistat are approved for adolescents aged 12 and older. It is critical to note that all medications discussed herein are contraindicated during pregnancy.
Exploring Current Weight Loss Medications
The field of weight loss medications is continually evolving, with both established and newly developed options. Here’s an overview of commonly prescribed medications:
Semaglutide (Wegovy, Ozempic)
Semaglutide injections for weight management and diabetes treatment.
Semaglutide, marketed as Wegovy, is a GLP-1 receptor agonist. It gained FDA approval in 2021 for chronic weight management. Administered via injection, Wegovy is approved for adults and children 12+ with obesity (BMI ≥30 in adults, BMI ≥ 95th percentile for age and sex in children) or overweight adults (BMI ≥27) with related medical conditions. Dosage escalation over 16-20 weeks to reach the 2.4 mg target dose is recommended to mitigate side effects such as gastrointestinal issues, headache, dizziness, and fatigue.
Ozempic contains the same active ingredient, semaglutide, but is indicated for type 2 diabetes management.
Tirzepatide (Zepbound, Mounjaro)
Tirzepatide, known as Mounjaro for type 2 diabetes, is now available as Zepbound for obesity treatment in adults with a BMI of 30 or greater.
This medication is a dual GLP-1 and GIP receptor agonist. Similar to semaglutide, it functions by curbing appetite and is designed to be used alongside dietary changes and exercise for effective weight loss. It is also administered via injection.
Liraglutide (Saxenda)
Saxenda liraglutide injection pen used for daily weight management.
Liraglutide (Saxenda) is a daily injectable medication influencing gut hormones that signal fullness to the brain and reduce hunger. Dosages range from 0.6 mg to 3 mg daily. Patients may experience a 5–10% body weight reduction, particularly with higher doses.
Side effects can include nausea, diarrhea, constipation, vomiting, headache, appetite decrease, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, and renal insufficiency. It is contraindicated for individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.
Phentermine (Adipex, Suprenza)
Phentermine stands as the oldest and most frequently prescribed weight loss medication. Initially intended for short-term use to initiate weight loss, current guidelines support its use in long-term therapy. Phentermine can help patients achieve approximately 5% body weight loss.
In the US, phentermine is primarily available in the HCl formulation, in 15 mg and 30 mg strengths. Potential side effects include headache, overstimulation, hypertension, insomnia, rapid or irregular heart rate, and tremors.
Drug interactions are possible with monoamine oxidase (MAO) inhibitors, sympathomimetics, alcohol, adrenergic neuron-blocking drugs, and certain anesthetic agents.
Phentermine-topiramate (Qsymia)
Combining topiramate with phentermine, as in Qsymia, enhances appetite suppression and reduces cravings. This combination therapy increases efficacy compared to either drug alone.
Qsymia is suitable for adults with migraines and obesity. Patients may achieve an average weight loss of 5–10% of body weight.
Discontinuation is recommended if 5% weight loss is not achieved after 12 weeks at the maximum dose. Daily doses range from 3.75 mg/23 mg to 15 mg/92 mg in four strengths. Side effects can include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and stimulant sensitivity.
Naltrexone-bupropion (Contrave)
Naltrexone-bupropion (Contrave) combines an opioid receptor antagonist with an antidepressant to modulate brain pleasure-reward pathways, thus decreasing cravings and appetite. Weight loss of 5–10% of body weight is possible.
Dosage starts at one 8/90 mg tablet daily, gradually increasing to four tablets daily. Common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. Contrave is not suitable for patients with seizure disorders or those taking opioids for chronic pain.
Setmelanotide (Imcivree)
Setmelanotide (Imcivree) is a melanocortin-4 receptor agonist indicated for chronic weight management in adults and children aged 6 and older with obesity due to specific rare genetic disorders.
These conditions must be confirmed by genetic testing showing variants in POMC, PCSK1, or LEPR genes classified as pathogenic, likely pathogenic, or variants of uncertain significance (VUS).
Orlistat (Xenical and Alli)
Orlistat, available as prescription Xenical and over-the-counter Alli, is a lipase inhibitor in capsule form. It reduces dietary fat absorption by blocking fat-breakdown enzymes.
Undigested fat is eliminated from the body. Orlistat is intended for use with a reduced-calorie diet and to prevent weight regain.
Approximately 5% body weight loss may be achieved. The prescription dosage is one 120 mg capsule three times daily with fat-containing meals (during or up to 1 hour post-meal). The over-the-counter version is a 60 mg capsule taken with each fat-containing meal. Common side effects include oily rectal discharge, flatus with discharge, increased defecation, and fecal incontinence.
Hydrogel (Plenity)
Plenity hydrogel capsules, a medical device for weight management.
Plenity is a medical device, not a medication, FDA-cleared in 2019 for individuals with a BMI of 24 to 40. It has gained increased attention alongside GLP-1 receptor agonists.
Plenity capsules release a biodegradable, super-absorbent hydrogel in the stomach, promoting satiety and reducing food intake. Real-world studies indicate an average weight loss of 9%.
Detailed information on these weight loss medications is available in the Obesity Medicine Association’s Obesity Algorithm®.
Emerging Weight Loss Medications on the Horizon
Fueled by strong consumer demand and rising obesity rates, the weight loss medication market is poised for further expansion.
Lilly is developing orforglipron, an oral GLP-1 inhibitor. Retatrutide, an injectable, targets GLP-1, GIP, and glucagon receptors. Pfizer is also developing oral GLP-1 inhibitors. Amgen is trialing a drug candidate that acts as a GLP-1 receptor agonist and a GIP receptor antagonist, differentiating it from dual agonists like semaglutide.
Researchers are continuously investigating hormones like peptide YY to identify new medication targets for obesity.
Dr. Robert Kushner, in an interview with Endocrine News, highlighted the shift towards treating obesity as an endocrine disease with hormonal approaches, offering diverse treatment options for patients and providers.
Monoclonal antibodies, such as bimagrumab, are also being explored for obesity treatment, showing potential to increase muscle mass while reducing fat.
This expanding range of options will enable doctors to personalize treatments, matching patients with the most effective medications. For further insights into these advancements, OMA offers a course on Future Advances in Anti-Obesity Medications.
Frequently Asked Questions About Weight Loss Medications
How Effective Are Weight Loss Medications?
FDA-approved anti-obesity medications (AOMs) are safe, evidence-based treatments targeting specific physiological mechanisms to improve the disease. They are most effective when integrated into a comprehensive treatment plan. The extent of weight loss varies depending on the medication, individual health, and other factors.
Despite the growth in available medications, some have been withdrawn due to safety concerns or lack of efficacy.
What is the Strongest Weight Loss Prescription Medication?
Clinical studies indicate significant weight loss with semaglutide. A 2022 study showed 5.9% weight loss at three months and 10.9% at six months. A larger study in the New England Journal of Medicine reported an average loss of 14.9%. However, semaglutide has drawbacks including high cost, side effects, and the need for long-term treatment.
Individual responses to medications vary. The optimal approach involves collaboration between patient and doctor to find the most effective treatment combination.
In 2022, the American Gastroenterological Association recommended several first-line weight loss medications for patients not responding adequately to lifestyle changes:
- Semaglutide
- Liraglutide
- Phentermine-topiramate extended-release (ER)
- Naltrexone-bupropion extended-release (ER)
They also recommended phentermine and diethylpropion. These recommendations preceded the approval of Zepbound.
How Do Weight Loss Medications Work?
Weight loss medications primarily function by regulating hormones in the brain, digestive system, and adipose tissue to reduce appetite and cravings and increase satiety.
Medications are available in oral and injectable forms. While patients often inquire about pills versus injections, especially concerning GLP-1 RAs, recent data suggests comparable effectiveness between oral and injectable options.
Are There Medications That Can Cause Weight Gain?
Yes, many medications can be obesogenic or contribute to weight gain, including:
- Certain beta-blockers and calcium channel blockers
- Anti-diabetes medications like insulins, sulfonylureas, thiazolidinediones, and meglitinides
- Hormone therapies such as glucocorticoids and injectable progestins
- Anti-seizure medications like carbamazepine, gabapentin, valproate, and pregabalin
- Various antidepressants
- Some mood stabilizers
- Migraine medications like amitriptyline and paroxetine
- Certain antipsychotics
- Chemotherapeutic and anti-inflammatory agents
How Should Weight Loss Medications Be Used With Other Treatments?
Obesity treatment often involves a combination of approaches, including medication, diet, exercise, and surgery. Weight loss medications are most effective when combined with a healthy diet and exercise regimen. They can help manage hunger, cravings, and metabolic adaptation, even when patients are actively engaged in lifestyle modifications.
How Long Do Weight Loss Medications Need to Be Taken?
Duration of treatment varies. Some medications are for short-term use (e.g., up to 12 weeks), while others are approved for long-term management.
Long-term approved medications include orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy, Ozempic), and tirzepatide (Zepbound, Mounjaro).
Some medications require a gradual dose escalation over several months. Obesity is a chronic disease, and medication is often needed for ongoing management, not a temporary “cure.”
How Have Weight Loss Medication Options Changed Recently?
GLP-1 RAs are recent advancements in a long history of weight loss medication development. As understanding of weight gain physiology has improved, newer drugs targeting newly identified receptors and enzymes have emerged, often with better safety profiles and fewer psychological side effects. Medications targeting hunger and satiety signals have gained prominence. Research into drugs targeting metabolic tissues is ongoing, but clinical applications are still limited. Further developments and new medications are expected.
How Do Weight Loss Medication Costs Compare?
Costs vary significantly. Older medications with generic versions are generally more affordable. GLP-1 RAs are notably expensive; Wegovy’s annual cost is estimated around $13,600. Phentermine can be as low as $10.
Insurance coverage is a major factor influencing patient access to and choice of weight loss medications. Medicare typically does not cover weight loss drugs.
How Do They Affect Weight Regain?
AOMs can counteract metabolic adaptation and help prevent weight regain. After weight loss, the body’s metabolism changes, often increasing hunger hormones and decreasing satiety hormones and resting metabolic rate, promoting weight regain. If a patient achieves significant weight loss with AOMs and medication helps maintain weight loss, continuous medication use is often recommended for weight maintenance.
What Are the Differences Between OTC and Prescription Weight Loss Medications?
Alli (orlistat) is the only FDA-approved over-the-counter (OTC) weight loss medication. Other OTC products are supplements, unregulated by the FDA, and lack rigorous safety and efficacy studies.
Prescription medications are prescribed and monitored by healthcare professionals, allowing for personalized assessment, progress tracking, side effect management, and dosage adjustments as needed.
What Is the Connection Between Antidepressant Medication and Weight Loss?
Antidepressants have varying effects on weight. Some cause weight gain (weight-positive), some are weight-neutral, and bupropion (Wellbutrin) is weight-negative (can cause weight loss).
Different antidepressant categories and specific medications within those categories have different weight effects. For example, paroxetine (SSRI) is associated with higher weight gain compared to other SSRIs. Bupropion, however, is used to treat depression and aid in weight loss. Individual responses to antidepressants vary.
Which Weight Loss Medications Are Known for Suppressing Appetite?
FDA-approved appetite-suppressing medications include: Tirzepatide (Zepbound), Liraglutide (Saxenda), Naltrexone-Bupropion (Contrave), Phentermine-Topiramate (Qysmia), and stimulants like benzphetamine (Didrex™), diethylpropion (Tenuate™), phentermine (Adipex-P, ProFast), and phendimetrazine. Each medication affects appetite through different mechanisms.
For more in-depth information, explore our webinar on Optimizing Use of FDA Approved Anti-Obesity Medications.
Seeking obesity treatment? Find an obesity medicine specialist near you to help determine the best weight loss medications for your needs.
