Reviewed by Dr. Kyle Hoedebecke, MD
Written by Peter Arian
Published Dec 12, 2025
Peptides for weight loss: cutting through hype with real data
If you Google “peptides for weight loss,” you’ll find everything from life-changing obesity drugs to underground “research chemicals” mixed together like they’re the same thing.
At Bowery Clinic, we use peptides every day for weight, body composition, and longevity but we’re strict about the difference between:
- Incretin drugs like semaglutide and tirzepatide with large human trials and FDA-approved versions, and
- “Adjunct” peptides (GH-axis, visceral-fat–targeting, mitochondrial) that are still emerging, often off-label, and nowhere near as well studied.
This article walks through what the evidence actually says and how we think about these tools in a real clinic.
1. Incretin-based peptides: semaglutide, tirzepatide, liraglutide
These are the heavy hitters. They drive double-digit percentage weight loss in large randomized trials and have FDA-approved branded versions for obesity.
Semaglutide (GLP-1 agonist)
What it is
Semaglutide is a GLP-1 receptor agonist (GLP-1 RA). At a higher dose (2.4 mg weekly, marketed as Wegovy), it’s approved for chronic weight management in people with obesity or overweight plus at least one weight-related condition.PubMed Central
How it works
Key human data
Weight regain and chronicity
Tirzepatide (dual GIP/GLP-1 agonist)
What it is
Tirzepatide is a dual agonist of GIP and GLP-1 receptors. It is FDA-approved for chronic weight management (Zepbound) and for type 2 diabetes (Mounjaro).
Key human data
How it compares to Semaglutide
Head-to-head data and cross-trial comparisons generally show tirzepatide producing somewhat greater average weight loss than semaglutide at standard obesity doses (think roughly high-teens to low-twenties percent vs mid-teens for Semaglutide).
Clinically, Tirzepatide is currently the most potent single weekly injectable in this class, but it carries similar GI side effects (nausea, vomiting, diarrhea) and the same chronic-disease reality: stop it abruptly, and weight tends to come back.
Retatrutide (triple GIP/GLP-1/glucagon agonist – investigational)
Retatrutide is a triple agonist that activates receptors for GLP-1, GIP, and glucagon (GCGR) — sometimes called a “triple G” drug.
Regulatory status
As of December 2025, Retatrutide is investigational. Phase 2 and multiple phase 3 trials are ongoing; it is not yet broadly approved for chronic weight management.
How it works (simplified)
Phase 2 obesity trial (48 weeks, people with obesity)
New phase 3 data (obesity + knee osteoarthritis)
- Late-stage trial in patients with obesity and knee osteoarthritis:
Takeaway: Retatrutide is shaping up as the most powerful incretin-class drug so far in trials, but it’s still investigational and not yet part of routine clinical care.
The trick in triple agonists is:
- GLP-1R + GIPR → strong insulin, appetite suppression, slower gastric emptying, better glucose handling
- GCGR → higher energy expenditure + more fat oxidation
GH-axis and visceral-fat–targeting peptides
These are the peptides most people see in longevity clinics. They can be helpful in specific contexts, but the evidence for general weight loss is much weaker and often indirect.
Tesamorelin (GHRH analog – visceral fat reduction in HIV)
Tesamorelin is a synthetic analog of growth hormone-releasing hormone (GHRH). It is FDA-approved to reduce excess visceral abdominal fat in patients with HIV-associated lipodystrophy, not for general obesity.
Key human data
Important caveats
Tesamorelin can make sense when visceral fat, hepatic fat, and cardiometabolic risk are the main issues, but it is not a first-line obesity drug. Any off-label use requires careful counseling.
Sermorelin and other GHRH analogs
Sermorelin is a truncated analog of GHRH that stimulates the pituitary to release more endogenous GH. It’s not FDA-approved for obesity or anti-aging but is widely used off-label in longevity settings.
What the research shows
- In a 5-month randomized trial of nightly GHRH analog injections (Nle27-GHRH(1-29)-NH2) in adults aged 55–71, treatment:
- Activated the GH–IGF-1 axis and increased IGF-1 levels.
- Increased lean body mass, insulin sensitivity, and measures of well-being in men, but not in women.
- Other work in older adults found that GHRH administration improved skeletal muscle function and some aspects of body composition, though not necessarily scale weight.
- Secondary summaries note improvements in waist-to-hip ratio and suggest that Sermorelin may help increase lean mass and facilitate fat loss, but these are based on relatively small, older studies, not modern obesity trials.
Sermorelin is best thought of as:
- A tool to gently raise GH/IGF-1 in older adults with low GH activity
- Potentially helpful for lean mass, recovery, and metabolic health
It is not in the same league as Semaglutide or Tirzepatide for direct, predictable weight loss.
CJC-1295 and Ipamorelin (GH secretagogue combo)
What they are
- CJC-1295: a long-acting GHRH analog that increases GH and IGF-1.
- Ipamorelin: a ghrelin receptor agonist that triggers short GH pulses.
They’re often combined in longevity clinics with the idea of mimicking youthful GH pulse.
What the research actually says
- In healthy adults, single and multiple doses of CJC-1295 cause sustained, dose-dependent increases in GH and IGF-1, with effects lasting days after an injection, and an acceptable short-term safety profile.
- In GHRH-knockout mice, daily CJC-1295 maintained normal body composition and growth vs untreated controls, functioning essentially as GH-axis replacement.
- Ipamorelin studies confirm it generates brief, dose-dependent GH pulses with a terminal half-life around 2 hours, with little effect on cortisol or prolactin.
- Critically, reviews and clinical summaries emphasize that while hormone changes are clear, “hard outcomes” like fat mass, lean mass, and strength changes in otherwise healthy users are not well proven in robust randomized trials.
Our stance at Bowery
CJC-1295/Ipamorelin can be useful as:
- A recovery and sleep-support tool
- A potential lean-mass/metabolic adjunct in carefully selected patients
We do not present it as a primary fat-loss drug and are transparent that evidence on actual body composition change is still limited.
In practice, our approach to peptides for weight and body composition looks like this:
- Use 3 month Tirzepatide protocol as the backbone in patients who qualify and are comfortable with a chronic, medication-plus-lifestyle plan. These are the only agents here with consistent double-digit percent weight loss in large human trials.
- Layer in adjuncts like Tesamorelin, Sermorelin, or CJC-1295/Ipamorelin only when there’s a clear rationale: visceral fat/liver fat focus, GH-axis support in older adults, or specific performance/recovery goals — and with explicit discussion that evidence for direct fat loss is limited.
- Keep sourcing and safety tight: only licensed pharmacies, full review of history (pancreatitis, gallbladder disease, thyroid cancer history, cardiovascular risk, current meds), and realistic expectations around weight regain if medication is stopped.
- Never present peptides as a magic fix. They are tools that make caloric and behavioral change more realistic — not substitutes for those changes.
Our Approach
At Bowery Clinic, we work exclusively with licensed 503A compounding pharmacies to ensure every medication meets the highest safety, purity, and sterility standards. We do not use or endorse research-grade peptides in any form, as they are not manufactured for human use and lack the regulatory protections required for safe medical treatment.
All treatments are prescribed and monitored by a licensed doctor, who reviews your history and goals to determine whether a peptide or compounded medication is appropriate for you and how it should be dosed and followed over time.
