Best Peptides for Fat Loss (2026)
Fat loss peptides work through diverse mechanisms: GH fragments that directly stimulate lipolysis (AOD-9604), GHRH analogs that increase fat-burning growth hormone (tesamorelin), mitochondrial peptides that enhance metabolic efficiency (MOTS-c), and GH secretagogues that optimize body composition through natural GH elevation. This guide focuses on peptides targeting fat metabolism specifically, separate from the GLP-1 receptor agonists covered in our weight loss guide, and examines the research evidence, mechanisms, and safety profiles for each approach. For a curated protocol, see the <a href="/stacks/fat-loss-stack">Fat Loss Stack</a>, or <a href="/tools/peptide-finder">take the Peptide Finder Quiz</a> to match compounds to your fat loss goals.
Last updated: 2026-02-20
Top Picks at a Glance
- 1.AOD-9604— GH fragment targeting fat metabolism without GH side effects
- 2.Tesamorelin— FDA-approved GHRH analog that selectively reduces visceral fat
- 3.MOTS-c— Mitochondrial peptide that acts as an exercise mimetic for metabolism
- 4.Ipamorelin— Selective GH secretagogue that improves body composition with minimal side effects
Fat Loss Peptides vs. Weight Loss Peptides
Fat loss and weight loss are related but distinct goals, and the peptides that target each work through fundamentally different mechanisms:
- Weight loss peptides (GLP-1 agonists like tirzepatide and retatrutide) reduce total body weight primarily through appetite suppression and reduced caloric intake. They produce the largest scale-weight changes (15–25% body weight in clinical trials) but may also reduce lean muscle mass. These are covered in our peptides for weight loss guide.
- Fat loss peptides (AOD-9604, tesamorelin, ipamorelin, MOTS-c) target fat metabolism specifically — stimulating lipolysis, inhibiting lipogenesis, or optimizing hormonal signals that promote fat oxidation. They typically preserve or increase lean mass while reducing fat mass, making them better suited for body recomposition goals.
The distinction matters because total body weight includes muscle, water, and bone in addition to fat. A person focused on body composition (lower body fat percentage, more muscle definition) may prefer fat-loss-specific peptides, even if the scale changes are more modest than with GLP-1 agonists.
How Fat Loss Peptides Work: Mechanisms Explained
Fat loss peptides target fat metabolism through several distinct biological pathways. Understanding these mechanisms helps clarify why different peptides suit different goals and why researchers sometimes combine approaches.
1. Direct lipolysis stimulation (AOD-9604):
AOD-9604 acts directly on adipocytes (fat cells) to stimulate the breakdown of stored triglycerides into free fatty acids and glycerol. This process — lipolysis — is the first step in fat burning. Simultaneously, AOD-9604 inhibits lipogenesis (the process by which the body converts excess calories into stored fat). This dual action means more fat is released from storage and less new fat is deposited.
2. Growth hormone optimization (tesamorelin, ipamorelin, sermorelin):
Growth hormone is one of the body's primary fat-mobilizing hormones. GH promotes lipolysis, enhances fat oxidation in the liver and muscles, and preserves lean tissue during caloric restriction. GHRH analogs (tesamorelin) and GH secretagogues (ipamorelin) increase natural GH production, restoring the fat-burning hormonal environment that declines with age (~14% per decade after 30).
3. Metabolic efficiency enhancement (MOTS-c):
MOTS-c activates AMPK, the cellular energy sensor that serves as a metabolic master switch. AMPK activation increases glucose uptake, fat oxidation, and mitochondrial biogenesis — essentially making cells more efficient at burning fuel. This "exercise mimetic" effect improves the body's baseline metabolic rate.
4. Visceral fat targeting (tesamorelin):
Tesamorelin is unique in its ability to selectively reduce visceral adipose tissue (VAT) — the metabolically dangerous fat surrounding internal organs. VAT is closely linked to insulin resistance, cardiovascular disease, and chronic inflammation. Tesamorelin's GH-mediated mechanism preferentially mobilizes visceral fat over subcutaneous fat.
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Fat Loss Peptide Comparison Table
The following table compares the key fat loss peptides across their mechanisms, evidence levels, and best use cases:
| Peptide | Mechanism | Best For | Typical Dose | Evidence Level |
|---|---|---|---|---|
| AOD-9604 | Direct lipolysis, anti-lipogenesis | General fat reduction, minimal hormonal impact | 250–500 mcg/day (fasted) | Clinical trials + GRAS status |
| Tesamorelin | GH stimulation via GHRH pathway | Visceral fat, liver fat, body recomposition | 2 mg/day | FDA-approved |
| MOTS-c | AMPK activation, metabolic optimization | Metabolic efficiency, insulin sensitivity | 5–10 mg, 3x/week | Preclinical + early clinical |
| Ipamorelin | Selective GH secretion (ghrelin receptor) | Body recomposition, lean mass preservation | 100–300 mcg, 2–3x/day | Preclinical + clinical |
Note: Tesamorelin is the only peptide in this table with full FDA approval for a fat-loss indication. Others remain research compounds. Use the peptide calculator for accurate reconstitution dosing.
How to Choose the Right Fat Loss Peptide
Selecting the right fat loss peptide depends on your specific goals, body composition, and existing health profile:
- For visceral fat (belly fat around organs): Tesamorelin has the strongest evidence with FDA approval specifically for visceral fat reduction. If visceral adiposity is the primary concern — particularly if metabolic markers (fasting glucose, triglycerides, liver enzymes) are elevated — tesamorelin has the most targeted evidence.
- For general fat loss with minimal hormonal impact: AOD-9604 offers a direct fat metabolism approach without affecting IGF-1, blood sugar, or other hormonal axes. Its GRAS status and favorable safety profile make it a lower-intervention option for those seeking modest, targeted fat reduction.
- For body recomposition (lose fat, keep/gain muscle): GH secretagogues like ipamorelin promote both lipolysis and lean mass preservation. By increasing natural GH production, they create an anabolic environment that favors muscle retention even during caloric restriction.
- For metabolic optimization: MOTS-c addresses the underlying metabolic inefficiency that often accompanies aging and sedentary lifestyles. If insulin resistance or poor metabolic flexibility is part of the picture, MOTS-c's AMPK activation may address root causes rather than just symptoms.
- For maximum fat loss regardless of approach: GLP-1 agonists (tirzepatide, retatrutide) produce the largest total fat loss, but through appetite suppression rather than direct metabolic targeting. See the weight loss guide.
Safety and Side Effects
Each fat loss peptide class carries its own safety profile. Understanding these helps make informed decisions:
AOD-9604: Has shown a favorable safety profile in clinical studies, with no significant adverse effects beyond mild injection site reactions. Its GRAS status from the FDA reflects its safety at studied doses. No effects on blood sugar, IGF-1, or tissue growth have been observed, distinguishing it from full-length growth hormone.
Tesamorelin: As an FDA-approved medication, tesamorelin has the most comprehensive safety data. Common side effects include injection site reactions (redness, itching), joint pain, and peripheral edema (swelling). It increases IGF-1 levels and should not be used in patients with active malignancies. Monitoring of IGF-1, fasting glucose, and HbA1c is recommended during use.
GH secretagogues (ipamorelin, CJC-1295): Can cause water retention, joint stiffness, and transient blood sugar elevations, particularly early in use. Ipamorelin has a cleaner side-effect profile than other secretagogues (GHRP-2, GHRP-6) because it does not significantly elevate cortisol or prolactin. Long-term GH elevation carries theoretical concerns related to cell proliferation, making periodic IGF-1 monitoring important.
MOTS-c: As a mitochondrial-derived peptide naturally present in the body, MOTS-c is expected to have a favorable safety profile. However, human safety data is very limited. Preclinical studies have not revealed concerning toxicity, but caution is warranted given the early stage of research.
General recommendations:
- Work with a healthcare provider who can monitor relevant biomarkers (IGF-1, fasting glucose, liver enzymes)
- Source peptides from reputable suppliers with third-party COAs
- Follow proper reconstitution and storage procedures
- Start with conservative doses and titrate based on response and tolerance
Fat Loss Peptides: Detailed Breakdown
AOD-9604
AOD-9604 is a modified 16-amino-acid fragment of human growth hormone (amino acids 176–191) designed to retain the lipolytic (fat-burning) properties of GH while eliminating the growth-promoting and diabetogenic effects. It stimulates lipolysis (fat breakdown) and inhibits lipogenesis (fat storage) through a mechanism distinct from the GH receptor.
Research published in the Journal of Endocrinology demonstrated that AOD-9604 increased fat oxidation in obese mice without affecting blood sugar or IGF-1 levels (PMID: 11713229). Its FDA GRAS (Generally Recognized as Safe) status for a food supplement application reflects its favorable safety profile at studied doses.
Key research findings:
- Stimulates lipolysis without affecting IGF-1 levels or blood glucose
- Inhibits lipogenesis (new fat storage) in adipose tissue
- No evidence of antibody formation or tolerance development in clinical studies
- Human clinical trials showed modest but statistically significant fat loss
- Emerging research for cartilage repair (intra-articular formulation under study)
AOD-9604 is typically studied at 250–500 mcg daily, administered subcutaneously in a fasted state (ideally morning, before eating). See the reconstitution guide for preparation instructions.
Tesamorelin
Tesamorelin is a growth hormone-releasing hormone (GHRH) analog that has FDA approval (brand name Egrifta) for reducing excess visceral abdominal fat in HIV-positive patients with lipodystrophy. It is the only FDA-approved treatment specifically targeting visceral adipose tissue (VAT) — the metabolically dangerous fat surrounding internal organs.
Unlike exogenous growth hormone, tesamorelin stimulates the body's own GH production through the pituitary gland, maintaining natural feedback loops. Clinical trials demonstrated 15–18% visceral fat reduction at 26 weeks, along with significant improvements in hepatic fat and metabolic markers (PMID: 20739384).
Key research findings:
- FDA-approved at 2mg daily for visceral fat reduction
- Reduces trunk fat by 15–18% in clinical trials while preserving lean mass
- Decreased liver fat by 37% in patients with NAFLD
- Increases IGF-1 levels by 50–100%, supporting body composition optimization
- Does not cause the insulin resistance commonly seen with exogenous GH
Tesamorelin is administered as a 2mg daily subcutaneous injection, typically in the evening. The dosage calculator can help with protocol planning.
MOTS-c
MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome — making it one of the few known mitochondrial-derived peptides (MDPs). It activates AMPK (AMP-activated protein kinase), the same metabolic master switch activated by exercise and caloric restriction. AMPK activation promotes glucose uptake, fat oxidation, and mitochondrial biogenesis.
Research by Dr. Changhan Lee's lab at USC showed MOTS-c improved insulin sensitivity, promoted glucose uptake in skeletal muscle, and enhanced fat oxidation in both cell and animal studies. Notably, plasma MOTS-c levels decline significantly with age, correlating with the metabolic dysfunction and increased adiposity seen in aging (PMID: 25738459).
Key research findings:
- Activates AMPK — the metabolic sensor that promotes fat burning and glucose uptake
- Improves insulin sensitivity and prevents diet-induced obesity in animal models
- Plasma levels decline with age, correlating with metabolic decline
- Functions as an "exercise mimetic" — activating metabolic pathways similar to physical exercise
- Promotes mitochondrial biogenesis (creation of new mitochondria) in cells
MOTS-c is an earlier-stage research compound compared to tesamorelin or AOD-9604. Typical research protocols use 5–10 mg injected subcutaneously several times per week.
Ipamorelin
Ipamorelin is a selective growth hormone secretagogue that stimulates GH release through the ghrelin receptor (GHS-R1a). What distinguishes ipamorelin from other GH secretagogues is its high selectivity — it stimulates GH release without significantly affecting cortisol, prolactin, or aldosterone levels, giving it a cleaner side-effect profile.
By increasing natural GH output, ipamorelin promotes lipolysis (fat breakdown), supports lean mass preservation during caloric restriction, and enhances overall metabolic efficiency. Research suggests it is particularly valuable for body recomposition (simultaneously losing fat and maintaining or gaining muscle) rather than pure scale weight reduction.
Key research findings:
- Selective GH release without affecting cortisol, prolactin, or aldosterone
- Does not significantly increase appetite (unlike other ghrelin mimetics like GHRP-6)
- Promotes lipolysis and lean mass preservation during caloric restriction
- Often combined with CJC-1295 for synergistic, sustained GH elevation
Ipamorelin is typically studied at 100–300 mcg subcutaneously, 2–3 times daily, with the most important dose before bedtime to amplify the natural nocturnal GH pulse.