If you’re wondering about the best weight loss medications, it’s vital to understand that “best” depends on individual goals, health conditions, and medical supervision. Below is a clear, evidence-backed overview of the most effective and approved options as of September 2025.
FDA‑Approved Weight Loss Medications
According to current medical guidelines and regulatory approvals, these medications are approved by the U.S. Food and Drug Administration (FDA) for weight management:
- Semaglutide (Wegovy) – a GLP‑1 receptor agonist, typically results in a 6–12% placebo‑adjusted weight loss WikipediaDrugs.com.
- Tirzepatide (Zepbound/Mounjaro) – a dual GIP/GLP‑1 receptor agonist, with high-dose regimens showing over 20% average weight loss at 72 weeks WikipediaThe SunSemaglutide ThailandVerywell Health.
- Phentermine/topiramate (Qsymia) – approved as part of a comprehensive diet-and-exercise plan Wikipedia.
- Naltrexone/bupropion (Contrave/Mysimba) – offers around 6% weight loss over 52 weeks Wikipedia+1.
- Orlistat – reduces fat absorption via lipase inhibition; studies show moderate weight loss (~2.9 kg on average) Wikipedia.
- Liraglutide (Saxenda) – another GLP‑1 agonist, FDA-approved for weight loss (not detailed above but included via general FDA approvals) Drugs.com.
Head‑to‑Head: Tirzepatide vs. Semaglutide
Efficacy
- Clinical trials show that tirzepatide yields significantly greater weight loss than semaglutide:
- At 72 weeks: 20.2% weight loss vs. 13.7% with Wegovy The Sun.
- Meta‑analyses confirm a stronger effect for tirzepatide PubMed+1.
- JAMA data: at 12 months, tirzepatide led to ~15.3% weight loss vs. ~8.3% for semaglutide; with adjusted differences of −6.9% JAMA Network.
- In real-world data, tirzepatide users had higher odds of achieving 5%, 10%, or 15% weight loss:
- 81.8% vs. 66.5% reaching ≥5%,
- 62.1% vs. 37.1% ≥10%,
- 42.3% vs. 18.1% ≥15% within a year PMC.
Cost-Effectiveness
- Tirzepatide appears more cost-effective per 1% body weight reduction:
Safety & Side Effects
- Both medications have similar safety profiles, with gastrointestinal symptoms (nausea, vomiting, diarrhea) being the most common PubMedHealor – Primary CareDrugs.com.
- No significant difference in GI adverse events between the two JAMA Network.
Emerging and Novel Options (Still Under Study)
Orforglipron (Oral GLP‑1 Agonist)
- A daily oral, non‑peptide GLP‑1 receptor agonist under development by Eli Lilly.
- Phase II/III data shows promising efficacy and a tolerable safety profile, though GI effects were common Wikipedia.
Cagrilintide + Semaglutide (CagriSema)
- A dual‑mechanism injectable combining amylin analog (cagrilintide) + semaglutide.
- Phase III trial (REDEFINE‑1) showed ~20.4% weight loss over 68 weeks—exceeding semaglutide alone (~14.9%) and cagrilintide alone (~11.5%) Wikipedia.
Retatrutide (Triple Agonist)
- Targets GIP, GLP‑1, and glucagon receptors.
- Phase III trials are ongoing (completion expected ~2026), with earlier data suggesting up to ~24% weight loss at 48 weeks GoodRx.
Summary Table
| Medication | Mechanism | Typical Weight Loss | Notes |
|---|---|---|---|
| Tirzepatide (Zepbound) | GIP/GLP‑1 dual agonist | ~20% at 72 weeks | Most effective, cost-efficient option |
| Semaglutide (Wegovy) | GLP‑1 agonist | ~12–15% over ~68 weeks | Strong efficacy, better CVD data |
| Phentermine/Topiramate | Appetite suppressants | ~? (varies) | Combination therapy |
| Naltrexone/Bupropion (Contrave) | Opiate antagonist + antidepressant | ~6% over 52 weeks | Oral, behavioral component |
| Orlistat | Lipase inhibitor | ~3 kg average loss | Over-the-counter option, GI side effects |
| Liraglutide (Saxenda) | GLP‑1 agonist | Moderate (not specified) | Daily injection alternative |
| Orforglipron | Oral GLP‑1 agonist (small molecule) | Early data positive | Upcoming oral agent |
| CagriSema | Amylin + GLP‑1 analog combination | ~20.4% over 68 weeks | In trial phases, promising |
| Retatrutide | GIP/GLP‑1/Glucagon triple agonist | ~24% at 48 weeks (est.) | Phase III, not available yet |
Key Takeaways
- Currently, tirzepatide (Zepbound/Mounjaro) appears to offer the greatest weight loss, with strong evidence for both efficacy and value, though long-term data is still being collected.
- Semaglutide (Wegovy) remains a highly effective option, particularly with solid data for cardiovascular benefits Barron’sDrugs.com.
- Older medications like Contrave, Qsymia, and Orlistat still serve a role—especially when injectable treatments are not viable.
- Emerging treatments such as orforglipron, CagriSema, and retatrutide show high potential but are not yet approved or widely available.
Final Thoughts
Choosing the right medication depends on your overall health, tolerance, access, and insurance coverage. Always consult a qualified healthcare provider to:
- Review potential side effects, contraindications, and interactions.
- Combine medication with lifestyle changes like diet and activity for sustainable success.
- Monitor progress regularly—these medications typically work best alongside comprehensive support.
Would you like help exploring lifestyle strategies that work in tandem with these medications, or guidance on how they’re prescribed in Thailand or your local area?
