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Ranked by evidence quality
1. Semaglutide (Wegovy, Ozempic)
GLP-1 receptor agonist. STEP 1 trial: 14.9% mean weight loss at 2.4mg/week over 68 weeks. FDA-approved for chronic weight management 2021. Strongest cardiovascular outcomes data (SELECT trial: 20% MACE reduction).
2. Tirzepatide (Zepbound, Mounjaro)
Dual GLP-1/GIP agonist. SURMOUNT-1: 20.9% mean weight loss at 15mg/week over 72 weeks. FDA-approved for obesity 2023. Superior weight loss vs semaglutide in head-to-head data.
3. Retatrutide (investigational)
Triple agonist (GLP-1 + GIP + glucagon). Phase 2: 24.2% mean weight loss at 12mg/week over 48 weeks. Phase 3 trials ongoing; FDA approval anticipated 2026-2027.
4. Liraglutide (Saxenda)
Daily GLP-1 agonist. Mean weight loss ~5-8%. FDA-approved 2014. Less effective than weekly semaglutide but useful for patients needing daily titration control.
5. Tesamorelin (Egrifta)
Stabilized GHRH analog. FDA-approved specifically for HIV-associated lipodystrophy. Studied off-label for visceral fat reduction in other populations. Does not produce general weight loss like GLP-1 drugs.
6. AOD9604
Modified HGH fragment (176-191). Marketed as targeting fat metabolism without affecting glucose. Clinical evidence in humans is weak — original Phase 2 obesity trials failed to show meaningful weight loss vs placebo.
7. HGH Fragment 176-191
Similar to AOD9604. Animal models show effects on adipose tissue; human evidence is limited.
8. CJC-1295 + Ipamorelin stack
GH secretagogue stack. Indirect effects on body composition via elevated IGF-1. Not a primary weight loss intervention but may shift body composition with sustained use.
Comparison table
| Peptide | Status | Mean weight loss | Mechanism |
|---|---|---|---|
| Tirzepatide | FDA-approved | ~21% | GLP-1/GIP |
| Semaglutide | FDA-approved | ~15% | GLP-1 |
| Retatrutide | Phase 3 | ~24% (Ph 2) | GLP-1/GIP/Glucagon |
| Liraglutide | FDA-approved | ~5-8% | GLP-1 (daily) |
| AOD9604 | Research | Negligible | HGH fragment |
How to choose
For evidence-based weight management, FDA-approved GLP-1 agonists are the standard. Tirzepatide produces the largest average effect; semaglutide has the most cardiovascular outcomes data. Both require weekly subcutaneous injection and dose titration over 12-20 weeks.
Non-FDA-approved peptides (AOD9604, HGH fragments, peptide stacks) do not have evidence comparable to GLP-1 drugs and should not be considered substitutes for evidence-based therapy.
Which peptide produces the most weight loss?<br />
In published data: tirzepatide (~21% at 72 weeks) > semaglutide (~15% at 68 weeks). Retatrutide showed ~24% in Phase 2; Phase 3 data is pending.
Are non-GLP-1 weight loss peptides effective?<br />
Evidence for AOD9604, HGH Fragment 176-191, and similar non-GLP-1 peptides is weak. Most failed to show meaningful weight loss in controlled human trials.
Do you regain weight after stopping?<br />
Yes. STEP 4 (semaglutide) and SURMOUNT-4 (tirzepatide) showed ~two-thirds of lost weight regained within 12 months of discontinuation. Long-term therapy is required to maintain effect.
Can weight loss peptides be combined?<br />
No — combining two GLP-1 agonists doesn’t produce additive effect, just additive side effects. Tesamorelin (GHRH) can theoretically be combined with GLP-1 drugs but evidence is limited.
Related GLP-1 guides: Compare semaglutide vs tirzepatide, read the full retatrutide guide, and explore the CJC-1295 & ipamorelin stack.