Every Weight Loss Medication Compared: GLP-1s, Phentermine, Contrave, and More

The FDA has approved more weight loss medications in the past five years than in the previous two decades combined. For patients navigating their options, the landscape can feel overwhelming. This guide compares every currently available FDA-approved weight loss medication by efficacy, safety profile, cost, and practical considerations.

The quick comparison

GLP-1 receptor agonists: the current gold standard

GLP-1 medications have fundamentally changed obesity medicine. They work by mimicking a natural gut hormone that regulates appetite, producing weight loss 2-4x greater than older medications. For detailed GLP-1 information, see our comprehensive GLP-1 guide.

Best for: Most patients with BMI ≥ 30 (or ≥ 27 with comorbidities) seeking substantial, sustained weight loss. Patients who want once-weekly dosing convenience.

Not ideal for: Patients with personal/family history of medullary thyroid carcinoma, pancreatitis, or those who cannot tolerate injections and prefer oral medication.

Phentermine-Topiramate (Qsymia): the oral alternative

Qsymia combines a low-dose appetite suppressant with topiramate, an anticonvulsant that independently reduces appetite. At ~9.8% average weight loss, it's the most effective oral option — bridging the gap between older drugs and GLP-1s.

Pros: Oral dosing, decent efficacy, available as generic in some formulations

Cons: Controlled substance (Schedule IV), contraindicated in pregnancy (topiramate causes birth defects), cognitive side effects ("topiramate fog"), limited to short-term use in some guidelines, cardiovascular risk profile requires monitoring

Naltrexone-Bupropion (Contrave): the craving reducer

Contrave targets the brain's reward system through a different mechanism than GLP-1s. Naltrexone blocks opioid receptors (reducing food-as-reward signaling) while bupropion acts on dopamine and norepinephrine pathways. It's particularly useful for patients whose eating is driven by emotional or reward-seeking patterns rather than physiological hunger.

Pros: May reduce emotional eating, dual antidepressant effect beneficial for some patients, no injection required

Cons: Modest weight loss (6.1%), common nausea, contraindicated with opioids, seizure risk with bupropion, complex titration schedule

Orlistat (Xenical/Alli): the fat blocker

Orlistat inhibits pancreatic lipase, blocking absorption of approximately 30% of dietary fat. Available as prescription Xenical (120mg) or OTC Alli (60mg). While modest in efficacy, it has one of the longest safety records of any weight loss medication.

Pros: Available OTC (Alli), long safety track record, no systemic absorption, no CNS effects

Cons: Modest results (~5%), unpleasant GI side effects (oily stools, fecal urgency), requires low-fat diet compliance, three-times-daily dosing, can reduce absorption of fat-soluble vitamins

Phentermine (Adipex-P): the classic stimulant

Phentermine has been FDA-approved since 1959, making it the oldest weight loss medication still in use. It works by stimulating norepinephrine release, suppressing appetite through a stimulant mechanism. FDA approval is for short-term use only (up to 12 weeks), though some physicians prescribe it longer off-label.

Pros: Inexpensive (generic available), rapid appetite suppression, decades of clinical experience

Cons: Controlled substance (Schedule IV), short-term approval only, stimulant side effects (insomnia, dry mouth, elevated heart rate), contraindicated with heart disease, tolerance develops

What the data means for your decision

For most patients meeting eligibility criteria, GLP-1 medications are the clear first choice based on efficacy, cardiovascular benefit, and tolerability. The key question is usually affordability, not effectiveness. For a detailed medication comparison tool, visit our compare page.

Our physicians help you choose the right medication based on your medical history, goals, insurance coverage, and budget. Start with a free screening to discuss your options.

Medically reviewed by the Linux Health Clinical Team. Updated July 2026. All medications require a physician prescription. Efficacy data from published clinical trials; individual results vary.