The FDA-approved obesity medications are the incretin drugs semaglutide and tirzepatide and the older daily liraglutide; the combinations phentermine/topiramate (Qsymia) and naltrexone/bupropion (Contrave); the lipase inhibitor orlistat; short-term phentermine; and setmelanotide for specific rare genetic obesity. They differ widely in mechanism, route and effect.
Hub page. Section accent: family --teal.
How to use this library
Every drug in this library gets its own page, built on one template: a fact panel (ingredient, mechanism, indication, route, titration concept, trial-contextualised effect, evidence grade) followed by how it works, what the trials actually show, side effects, contraindications, monitoring, pregnancy, discontinuation and weight regain, and unanswered questions.
Three standing rules apply on every page:
- No drug is universally best. The right medication depends on the person — comorbidities, prior response, tolerability, pregnancy plans, contraindications, access and goals. A more potent drug is not automatically the right one. → The W8Experts Clinical Approach
- Effect sizes are trial averages, not personal predictions. We always attach the drug, dose, trial, population and duration, and separate total from placebo-adjusted loss. → GLP-1 hub: how to read weight-loss numbers
- These pages are educational, not prescriptions. Titration and suitability are set by a clinician, never by a web page.
The approved agents at a glance
| Medication (brand) | Mechanism | Route | Approximate effect | Key indication / who it's for |
|---|---|---|---|---|
| Semaglutide (Wegovy, oral Wegovy 25 mg) | GLP-1 receptor agonist | Weekly injection; oral daily | ~15% mean total loss at 68 wk (STEP 1) | High-efficacy chronic weight management; CV risk reduction; MASH F2–F3 → Semaglutide |
| Tirzepatide (Zepbound) | GLP-1 / GIP dual agonist | Weekly injection | ~15–21% mean by dose at 72 wk (SURMOUNT-1) | Highest average efficacy; also OSA with obesity → Tirzepatide |
| Liraglutide (Saxenda) | GLP-1 receptor agonist | Daily injection | ~5–8% loss (less than weekly agents) | Daily incretin option; long track record → Liraglutide |
| Phentermine/topiramate (Qsymia) | Sympathomimetic + neurostabiliser | Oral daily | ~9–10% total at top dose, ~1 yr (CONQUER/EQUIP) — below GLP-1s | Combination oral therapy for chronic management → Phentermine/Topiramate |
| Naltrexone/bupropion (Contrave) | Opioid antagonist + dopamine/NE reuptake inhibitor (reward/appetite) | Oral daily | Modest — ~5–6% total (~4.8% placebo-subtracted), ~1 yr (COR) | Appetite/reward-driven eating; no stimulant → Naltrexone/Bupropion |
| Orlistat (Xenical Rx, Alli OTC) | Intestinal lipase inhibitor | Oral with meals | Modest — ~5% total (~3% above placebo), ~1 yr (XENDOS) | Non-systemic option; fat-blocking; OTC available → Orlistat |
| Phentermine (alone) | Sympathomimetic appetite suppressant | Oral daily | ~5% short-term (few weeks–months) | Short-term use only; long history → Phentermine |
| Setmelanotide (Imcivree) | MC4R pathway agonist | Daily injection | Specific to rare genetic obesity [verify] |
POMC, LEPR, Bardet-Biedl deficiency only → Setmelanotide |
Semaglutide and tirzepatide have their own dedicated chapters in the GLP-1 hub; this library links to them rather than duplicating them.
The tiers, honestly
The incretins (highest average efficacy). Semaglutide and tirzepatide, and to a lesser extent daily liraglutide, produce the largest average weight loss of any approved drugs and carry outcome evidence beyond weight (semaglutide: ~20% MACE reduction in SELECT; tirzepatide: OSA benefit). They anchor modern pharmacotherapy. → GLP-1 & Incretin Medications
The older oral agents (moderate to modest). Phentermine/topiramate (Qsymia) sits below the GLP-1s on average but above the other oral options; naltrexone/bupropion (Contrave) and orlistat are more modest. They remain useful — for patients who prefer a pill, can't tolerate or access incretins, or have a specific reason to target reward-driven eating (Contrave) or avoid systemic absorption (orlistat).
Short-term phentermine. Approved for short-term use, with a long history predating the modern era. It suppresses appetite via sympathomimetic action and carries cardiovascular cautions. → Phentermine
Setmelanotide (a category of its own). Not a general obesity drug at all — it is precision therapy for defined monogenic disease in the leptin–melanocortin pathway. It illustrates where obesity treatment is heading: matching mechanism to biology. → Genetics of Obesity
What this library does not cover
- Emerging and investigational agents — retatrutide, CagriSema, survodutide, orforglipron, amylin analogues and muscle-preserving drugs — live in the pipeline database, never presented as available treatments. → Emerging-Therapy Database · The Next Generation of Obesity Medicine
- Supplements and "natural Ozempic" products — evaluated separately and sceptically. → Weight-Loss Supplements · Natural & Alternative Approaches
- Compounded GLP-1s — a distinct safety and regulatory topic. → Compounded GLP-1s
Questions patients ask
What weight-loss medications are FDA-approved?
Semaglutide, tirzepatide and liraglutide (incretins); phentermine/topiramate (Qsymia); naltrexone/bupropion (Contrave); orlistat; short-term phentermine; and setmelanotide for specific rare genetic obesity. Grade A 🟢
Which one causes the most weight loss?
On average, tirzepatide, then semaglutide — the incretins lead. But "most" isn't "best for you": comorbidities, tolerability, pregnancy plans, contraindications and access all matter. Grade A 🟢 (efficacy) / B 🟡 (choice) → Semaglutide vs Tirzepatide
Is there a pill instead of an injection?
Yes — oral semaglutide 25 mg, plus the older oral drugs Qsymia, Contrave and orlistat. Orforglipron, an investigational oral, is not yet approved. Grade A 🟢 → Semaglutide
Do these drugs work without diabetes?
Yes — the obesity approvals are largely in people without diabetes, and average loss is generally greater without diabetes than with it. Grade A 🟢
Will I regain weight if I stop?
For every effective obesity drug studied, stopping tends to be followed by regain, because the underlying biology persists. Obesity is treated as a chronic disease. Grade A 🟢 → Weight Regain & Maintenance
Are the older, cheaper drugs worthless now?
No. Qsymia, Contrave, orlistat and phentermine remain reasonable options for patients who prefer a pill, can't access or tolerate incretins, or have a specific reason to use them. Grade B 🟡
KEEP READING
- GLP-1 & Incretin Medications — the highest-efficacy class, in depth.
- The W8Experts Clinical Approach — how we match a drug to a person, not a scale.
- The Next Generation of Obesity Medicine — what's coming, graded by phase.
- Weight Regain & Maintenance — why stopping usually means regain, whatever the drug.
- Weight-Loss Supplements — why "natural" alternatives don't belong in this library.
Written by Darius A. Schneider, MD, PhD · Board-Certified Endocrinologist (ECNU) · Last updated: 2026-08-10 · References: FDA prescribing information for the listed agents; STEP and SURMOUNT programs; SELECT; SURMOUNT-OSA. Educational only; not individualized medical advice.
