When someone asks, “What is the best weight‑loss drug?”, the answer depends on how you define “best”—whether it’s greatest weight loss, safety, heart‑health benefits, administration method, or availability. Here’s a breakdown of the current landscape as of September 2025:
Most Effective Approved Option: Tirzepatide (Zepbound / Mounjaro)
- Efficacy: Clinical trials show remarkable results—up to 20–22% average body weight loss over 72 weeks across 10–15 mg doses (AJMC, New York Post, TIME).
- Real-world Insights: Comparisons with semaglutide reveal tirzepatide’s superior efficacy: ~20.2% vs. ~13.7% weight loss in the same period (TIME).
- Ranking: Across multiple efficacy benchmarks, tirzepatide often topped them—especially for achieving ≥15% weight loss and improving cardiometabolic markers (Healio).
- Considerations: It’s an injectable and has common GI side effects. Coverage and availability vary based on region and insurance (Heally, CNBC).
Strong Contender with Heart-Health Edge: Semaglutide (Wegovy / Ozempic)
- Efficacy: Around 12–15% average weight loss, with some users experiencing over 20% (Wikipedia, ASAP Drew, TIME, CNN).
- Heart Health: A real-world study indicates Wegovy reduced the risk of heart attack, stroke, and death by 57% more than tirzepatide among patients with cardiovascular disease (Barron’s).
- Advantages: Has a well-established safety profile, strong long-term data, and widespread clinical use (ASAP Drew, Barron’s).
Emerging Therapies (Not Yet Approved)
Retatrutide
- A triple-agonist targeting GLP‑1, GIP, and glucagon receptors.
- Phase 2 trials report up to 24.2% average weight loss at 48 weeks (Wikipedia, Ithy).
- Still in Phase 3 trials, with no approval yet (ASAP Drew, Wikipedia).
CagriSema (Cagrilintide + Semaglutide)
- In a 68-week Phase III trial, users lost 20.4% body weight, compared to 14.9% with semaglutide alone (Wikipedia).
- Promising, but still investigational (ASAP Drew, Wikipedia).
Orforglipron (Oral GLP‑1 Agonist)
- A daily pill, not an injection.
- Phase III data shows notable weight loss—around 12–14% over 72 weeks—though slightly less than Wegovy (Reuters, The Times, Wikipedia, Childhood Obesity News, The Sun).
- Efficacy is still below the top injectables but offers easier administration and patient preference (ASAP Drew, Reuters, The Times).
Summary Table
| Drug / Therapy | Status | Approx. Weight Loss | Key Strengths |
|---|---|---|---|
| Tirzepatide (Zepbound) | Approved | ~20–22% over ~72 weeks | Highest proven efficacy |
| Semaglutide (Wegovy) | Approved | ~12–15% (some >20%) | Strong cardiovascular benefits |
| Retatrutide | Phase 3 trial | ~24% (Phase 2) | Triple mechanism; possibly most effective |
| CagriSema | Phase 3 trial | ~20.4% (68 weeks) | Combination amylin + GLP‑1 |
| Orforglipron (pill) | Phase 3 trial | ~12–14% | Oral dosing; more convenient |
Final Thoughts: What’s “Best” Depends on You
- For maximum weight loss today: Tirzepatide remains the strongest choice among approved options.
- If cardiovascular benefit matters: Semaglutide (Wegovy) offers a heart-health edge.
- Seeking the future now: Look out for retatrutide and CagriSema, pending further clinical results.
- Need a pill, not injection: Orforglipron may soon offer a more convenient route—once approved.
No drug works in isolation—combining medication with healthy lifestyle habits (diet, activity, sleep, support) is essential for safe and sustained results. Always consult a healthcare provider to determine which medication aligns best with your health needs and goals.
