Introduction
If you’re serious about your weight loss journey, you’ve probably heard about weight loss peptides. These compounds work in different ways to change body composition, boost fat metabolism, and help people lose weight, sometimes dramatically. Some are FDA approved, others are newer peptides still in clinical trials, and a few are research compounds that target mitochondrial function or enzymes.
Below are the top five peptides and peptide-adjacent compounds people ask about in 2025: Retatrutide, AOD9604, Tesamorelin, MOTS-C, 5-Amino-1MQ, plus a quick note on SLU-PP-332. I’ll explain what they do, who they help, what the data say about weight reduction, and common practical concerns like injection site reactions, lean muscle preservation, and safety.
1) Retatrutide | The big hitter for significant weight loss
What it is: Retatrutide is a triple agonist that works on GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors. That mix means it can reduce food intake, improve glycemic control, and increase energy expenditure.
How it helps fat loss:
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Reduces appetite and food intake, so you naturally eat less.
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Improves insulin sensitivity, lowering blood sugar spikes and supporting fat burning.
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Activates glucagon pathways to increase fat metabolism and energy production, helping to reduce body fat mass, especially abdominal fat.
Clinical evidence & results: In dose-dependent Phase-2 clinical trials, retatrutide produced significant weight loss (often 20%+ body weight at higher doses over months), outperforming many older agents. It’s still in trials and not yet widely FDA-approved for general obesity treatment, but it’s a real new hope for stubborn fat.
Real-world notes: Because effects are strong, starting dose and gradual escalation help reduce side effects like nausea. Work with a healthcare provider if you’re considering it.
2) AOD9604 | Targeted fat-burning fragment of growth hormone
What it is: AOD9604 is a fragment of human growth hormone developed specifically to stimulate lipolysis (fat breakdown) without majorly increasing overall growth hormone release.
How it helps fat loss:
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Promotes fat metabolism and targets stored fat, often touted for abdominal fat and stubborn fat.
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Acts in a dose-dependent manner in studies, helping reduce body fat mass without big shifts in insulin secretion.
Clinical evidence: Early trials and placebo group comparisons show modest weight reduction and reduced fat mass versus placebo or lifestyle alone. Evidence is mixed; AOD9604 has clinical evidence but less than GLP-1s or retatrutide.
Practical use: Often stacked into peptide therapy programs with exercise and a healthy diet to support lean muscle retention and better body composition.
3) Tesamorelin | A targeted, FDA-approved option for visceral fat
What it is: Tesamorelin is a growth hormone-releasing factor analog that increases growth hormone pulsatility from the pituitary gland.
How it helps fat loss:
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Specifically reduces visceral abdominal fat (the metabolically harmful fat around organs).
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It works by stimulating growth hormone, which can increase lipolysis and alter fat metabolism.
Clinical evidence & regulation: Tesamorelin is FDA-approved for treating HIV-associated lipodystrophy, a weight-related condition where abdominal fat is problematic. It’s not a general prescription-only medication for all people with obesity, but its safety profile and clinical trial record are strong in its approved indication.
Practical concerns: It can cause fluid retention or changes in blood sugar for some users. It’s delivered via subcutaneous injection and requires medical monitoring.
4) MOTS-C | A mitochondrial-derived peptide improving metabolic health
What it is: MOTS-C is a mitochondrial-derived peptide that acts like a metabolic signal, improving mitochondrial function and cellular energy.
How it helps fat loss:
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Enhances energy production and energy expenditure at the cellular level.
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Improves insulin sensitivity, helping reduce age-related insulin resistance and promoting more efficient fat burning.
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In animal models and early human work, MOTS-C reduces body weight, waist circumference, and visceral fat, while supporting lean muscle.
Clinical evidence: MOTS-C has strong preclinical evidence and growing human research suggesting benefits for metabolic health and sustainable results when combined with lifestyle intervention.
Practical use: Often considered a complement to appetite-reducing peptides, it helps the body use fat more efficiently (better metabolic flexibility) and supports the weight loss journey.
5) 5-Amino-1MQ & SLU-PP-332 | Enzyme and research-stage approaches
5-Amino-1MQ: Not a peptide but a small molecule that inhibits NNMT, an enzyme linked to metabolic inefficiency. In animal studies, it increases energy expenditure, improves insulin sensitivity, and causes rapid fat mass loss. Human data are limited, but it’s a promising metabolic target.
SLU-PP-332: An experimental compound under research for cell metabolism and fat burning. Like 5-Amino-1MQ, it represents the next wave: targeting metabolic enzymes and mitochondrial function rather than hormone receptors.
Practical note: Both are research-stage and not standard treatments. They point to future genetic engineering and metabolic-targeted strategies for weight management.
How do these peptides fit into a practical plan?
1. Mechanism matters: GLP-1/GIP/glucagon triple agonists (Retatrutide) reduce appetite and raise energy burn; AOD9604 targets lipolysis; Tesamorelin acts through growth hormone; MOTS-C supports mitochondrial-derived energy. 5-Amino-1MQ and SLU-PP-332 aim at enzyme pathways.
2. Combine with healthy habits: No peptide replaces a healthy diet, resistance training (to protect lean muscle), sleep, and stress control. Peptides work best as part of a lifestyle intervention.
3. Monitor outcomes: Track body weight, body fat mass, waist circumference, blood sugar, and blood pressure. Watch for injection site reactions and common potential side effects like nausea or fluid retention.
4. Safety & sourcing: Prefer FDA-approved agents if applicable. Avoid unmanaged compounded products and seek a qualified healthcare provider who can monitor labs and adjust dosing.
Who might benefit most?
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People with obesity or significant body mass index concerns.
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Those struggling with stubborn fat despite diet and training, especially abdominal fat.
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Anyone seeking metabolic health improvements — better insulin sensitivity, lower blood sugar, improved energy balance.
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Not a first-line quick fix: try lifestyle changes first, then consider peptide therapy under medical care.
Bottom line
Fat loss peptides are no longer niche. From the high efficacy potential of retatrutide to the targeted fat-burning of AOD9604, the metabolic support of MOTS-C, and the specific visceral fat effects of tesamorelin, there are now real, science-backed tools to help with weight reduction and metabolic health. Emerging enzyme targets like 5-Amino-1MQ and experimental compounds such as SLU-PP-332 expand the toolbox further.
Use peptides as part of a medical plan: set realistic weight loss goals, protect lean muscle, and aim for sustainable results with close monitoring and sensible lifestyle changes.