Metabolic Peptides — Reference Comparison Card
Semaglutide: 14.9% weight loss (STEP 1, PMID 33567185). Tirzepatide: 22.5% (SURMOUNT-1, PMID 35658024). Tesamorelin: 15–18% visceral fat reduction (PMID 20724674). AOD-9604: Grade D.
| Measure | Value | Unit | Notes |
|---|---|---|---|
| Highest Approved Weight Loss Effect | 22.5 | % body weight (tirzepatide) | SURMOUNT-1: tirzepatide 15mg/week × 72 weeks; current ceiling for approved pharmacotherapy |
| Semaglutide Weight Loss | 14.9 | % body weight | STEP 1 (PMID 33567185): 2.4mg/week × 68 weeks; GLP-1R agonist only |
| Tesamorelin Visceral Fat Reduction | 15–18 | % visceral adiposity | PMID 20724674: FDA-approved specifically for HIV-related lipodystrophy; no obesity approval |
| AOD-9604 Evidence Grade | D | grade | Failed Phase 3 for obesity (Metabasis trial); no approved indication; research chemical only |
| Peptides with FDA Approval | 3 | count | Semaglutide (Ozempic/Wegovy), tirzepatide (Mounjaro/Zepbound), tesamorelin (Egrifta) — all Rx only |
| AOD-9604 Fragment | 176–191 | hGH fragment position | C-terminal fragment of human growth hormone; lipolytic without IGF-1 axis activation — in theory |
Metabolic Peptide Comparison — Reference Card
This page is a reference table for the four main peptides discussed in the context of metabolic effects and fat loss: AOD-9604, tesamorelin, semaglutide, and tirzepatide. The table is ordered by evidence grade and clinical approval status.
Primary Comparison Table
| Peptide | Mechanism | Receptor Target | FDA Status | Approved Indication | Evidence Grade | Typical Route | Availability |
|---|---|---|---|---|---|---|---|
| Tirzepatide | Dual incretin agonist | GIP-R + GLP-1R | Approved 2022/2023 | T2D (Mounjaro); Obesity (Zepbound) | A | Subcutaneous weekly | Prescription Rx |
| Semaglutide | GLP-1 analogue | GLP-1R | Approved 2017/2021 | T2D (Ozempic); Obesity (Wegovy) | A | Subcutaneous weekly; oral | Prescription Rx |
| Tesamorelin | GHRH analogue | GHRH-R | Approved 2010 | HIV lipodystrophy only | B | Subcutaneous daily | Prescription Rx (limited) |
| AOD-9604 | hGH fragment | No direct receptor (lipolytic) | Not approved | None — failed Phase 3 | D | Subcutaneous daily (research) | Research chemical / gray market |
Efficacy Data Table
| Peptide | Key Trial | Duration | Primary Outcome | Effect Size | Comparator |
|---|---|---|---|---|---|
| Tirzepatide 15mg | SURMOUNT-1 (PMID 35658024) | 72 weeks | Mean % weight loss | −22.5% | −2.5% placebo |
| Tirzepatide 10mg | SURMOUNT-1 | 72 weeks | Mean % weight loss | −19.5% | −2.5% placebo |
| Semaglutide 2.4mg | STEP 1 (PMID 33567185) | 68 weeks | Mean % weight loss | −14.9% | −2.4% placebo |
| Tesamorelin 2mg | PMID 20724674 | 26 weeks | Visceral fat (CT) | −15–18% visceral | No change placebo |
| AOD-9604 | Metabasis Phase 3 | 24 weeks | Mean % weight loss | Not statistically significant | Placebo |
Mechanistic Differences
| Peptide | Primary Fat Loss Mechanism | Secondary Effects | IGF-1 Axis? | Insulin Mechanism |
|---|---|---|---|---|
| Tirzepatide | Dual incretin appetite suppression | Adipocyte lipolysis via GIPR | No | Insulin secretion (glucose-dependent) |
| Semaglutide | GLP-1R appetite suppression; gastric emptying delay | Glucagon suppression | No | Insulin secretion (glucose-dependent) |
| Tesamorelin | GHRH → GH → visceral lipolysis | Improved lipid profile | Mild IGF-1 elevation | No direct effect |
| AOD-9604 | Proposed direct lipolysis via beta-3 adrenergic | No systemic GH effects | No | No |
Legal Status by Jurisdiction
| Jurisdiction | Tirzepatide | Semaglutide | Tesamorelin | AOD-9604 |
|---|---|---|---|---|
| USA | Prescription Rx | Prescription Rx | Prescription Rx | Research chemical (unscheduled) |
| UK | Prescription Rx | Prescription Rx | Not approved | Not regulated |
| Australia | Schedule 4 Rx | Schedule 4 Rx | Not TGA-listed | Not listed (import gray area) |
| Canada | Schedule F Rx | Schedule F Rx | Not Health Canada listed | Gray market |
| EU | Prescription Rx | Prescription Rx | Not EMA-approved | Not harmonized |
Evidence Grade Callout
Grade A: Tirzepatide, Semaglutide — multiple Phase 3 RCTs, FDA/EMA approval, cardiovascular outcome data. Grade B: Tesamorelin — FDA-approved but for a narrow, specific population (HIV lipodystrophy); evidence does not generalize to general obesity. Grade D: AOD-9604 — failed primary endpoint in Phase 3; no approved indication; no peer-reviewed efficacy data in humans.
Legal Disclaimer
Tirzepatide, semaglutide, and tesamorelin are prescription pharmaceuticals requiring valid prescriptions. AOD-9604 has no approved indication in any jurisdiction and its use in humans outside of registered clinical trials is unsupported. This page is educational only and does not constitute medical advice.
Related Pages
Sources
- Jastreboff AM et al. Tirzepatide once weekly for obesity. N Engl J Med. 2022;387(3):205-216. PMID 35658024
- Falutz J et al. Effects of tesamorelin on visceral fat and liver fat in HIV-infected patients. AIDS. 2010;24(10):1449-57. PMID 20724674
- Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. PMID 33567185
Frequently Asked Questions
Which metabolic peptide has the strongest evidence for weight loss?
Tirzepatide has the highest evidence-supported weight loss magnitude: 22.5% mean body weight reduction at 15mg/week in the SURMOUNT-1 Phase 3 RCT (PMID 35658024), with FDA approval for obesity in 2023. Semaglutide (14.9% in STEP 1) is the second strongest with its own FDA approval. Tesamorelin reduces visceral fat specifically in HIV lipodystrophy but is not approved for general obesity. AOD-9604 failed Phase 3 trials and has no approved indication.
Can AOD-9604 be used for fat loss?
AOD-9604 has no FDA, EMA, TGA, or Health Canada approval for any indication. It was studied in a Phase 3 obesity trial (Metabasis) which did not meet its primary endpoint. There is no human trial data demonstrating meaningful fat loss in the general population. It is classified as a research chemical. Use of AOD-9604 for body composition in a clinical or therapeutic context is not supported by current evidence.
What is tesamorelin approved for?
Tesamorelin (Egrifta) is FDA-approved specifically for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy — a condition caused by antiretroviral therapy. It is a GHRH analogue that stimulates endogenous GH release, which reduces visceral adiposity by 15–18% in this specific population (PMID 20724674). It is not approved for general obesity or body composition enhancement, and off-label use is unsupported by adequate evidence.