Do Peptides Work for Weight Loss?
Some peptides produce the most dramatic weight loss results in pharmaceutical history. Others have no meaningful evidence behind them. The gap between what's proven and what's marketed is enormous — and knowing the difference can save you thousands of dollars and months of wasted time.
Some peptides produce the most dramatic weight loss results in pharmaceutical history. Others have no meaningful evidence behind them. The gap between what's proven and what's marketed is enormous — and knowing the difference can save you thousands of dollars and months of wasted time.
This guide covers every peptide used for weight loss, organized by the strength of evidence, with realistic expectations for each.
Table of Contents
- The Winners: GLP-1 Agonists (Strong Evidence)
- The Dual Agonist Era: Tirzepatide and Beyond
- Growth Hormone Peptides: Indirect Effects (Moderate Evidence)
- AOD-9604: The Disappointing Candidate (Weak Evidence)
- Other Peptides Marketed for Weight Loss
- What the Evidence Actually Shows for Each
- Realistic Expectations
- The Cost-Benefit Equation
- Frequently Asked Questions
- The Bottom Line
- References
The Winners: GLP-1 Agonists (Strong Evidence)
GLP-1 receptor agonists have redefined what's possible in pharmaceutical weight loss. These aren't modest improvements — they produce the largest sustained weight reductions ever seen from any drug.
Semaglutide (Wegovy)
Semaglutide 2.4mg once weekly is the current standard of care for pharmaceutical weight management.
The evidence:
- STEP 1 (1,961 participants, 68 weeks): Average weight loss of 14.9% vs. 2.4% for placebo. That's approximately 33 pounds for someone starting at 230 pounds.
- STEP 3 (611 participants, with intensive behavioral therapy): Average weight loss of 16.0% with semaglutide vs. 5.7% with placebo and behavioral therapy alone.
- STEP 5 (304 participants, 104 weeks): Sustained 15.2% weight loss at 2 years, demonstrating that the effect doesn't wear off with continued use.
- SELECT (17,604 participants, mean 39.8 months): 20% reduction in major adverse cardiovascular events, proving the weight loss translates to reduced heart attacks and strokes.
How it works: Semaglutide activates GLP-1 receptors throughout the body — in the pancreas (improving insulin secretion), the stomach (slowing gastric emptying), and the brain (reducing appetite and altering food reward pathways). The combined effect is powerful appetite suppression, earlier satiety, and reduced food cravings. Most patients describe it as simply not thinking about food as much.
The ICER assessment: The Institute for Clinical and Economic Review (October 2025) confirmed injectable semaglutide produces 13.1% weight loss compared to placebo — clinically and statistically significant.
Liraglutide (Saxenda)
Liraglutide 3.0mg daily was the first GLP-1 agonist approved specifically for weight management (2014).
The evidence: The SCALE trials showed average weight loss of approximately 8% over 56 weeks (vs. 2.6% for placebo). This is less dramatic than semaglutide but still clinically significant — enough to improve metabolic markers and reduce diabetes risk.
Current relevance: Saxenda has been largely eclipsed by once-weekly semaglutide (which produces more weight loss with less frequent dosing). It remains an option for patients who can't tolerate semaglutide or prefer daily dosing.
The Dual Agonist Era: Tirzepatide and Beyond
The next generation of weight loss peptides activates multiple hormone receptors simultaneously, producing even greater effects.
Tirzepatide (Zepbound)
Tirzepatide is a dual GIP/GLP-1 receptor agonist — it activates both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. This dual mechanism appears to produce additive weight loss effects.
The evidence:
- SURMOUNT-1 (2,539 participants, 72 weeks): Average weight loss of 15.0% (5mg), 19.5% (10mg), and 20.9% (15mg) vs. 3.1% for placebo. At the highest dose, the average patient lost 52 pounds.
- SURMOUNT-5 (head-to-head vs. semaglutide, 751 participants, 72 weeks): Tirzepatide produced 20.2% weight loss vs. 13.7% for semaglutide. This confirmed tirzepatide's superiority in a direct comparison.
- Nearly one-third (32%) of participants on tirzepatide achieved 25%+ weight loss — approaching what was previously achievable only through bariatric surgery.
The ICER assessment: Tirzepatide produces 17.8% weight loss compared to placebo — the largest of any anti-obesity medication.
What's Coming Next
Retatrutide is a triple agonist (GIP/GLP-1/glucagon receptor). Phase II trials showed up to 24.2% weight loss at 48 weeks — potentially exceeding tirzepatide. Phase III trials are ongoing. See our retatrutide profile.
CagriSema (Novo Nordisk) combines semaglutide with cagrilintide (an amylin analog). Phase III data is emerging, with expectations of weight loss exceeding semaglutide alone. See our CagriSema profile.
Survodutide (Boehringer Ingelheim) is a dual glucagon/GLP-1 agonist with Phase III trials underway. See survodutide research overview.
Orforglipron (Eli Lilly) is an oral, non-peptide GLP-1 agonist. Phase III trials showed 7.8-12.4% weight loss — less than injectable options but significant for a daily pill. See orforglipron profile.
For analysis of the evolving landscape, see next-generation GLP-1 drugs.
Growth Hormone Peptides: Indirect Effects (Moderate Evidence)
Growth hormone secretagogues — CJC-1295, ipamorelin, GHRP-2, GHRP-6, MK-677, tesamorelin — are sometimes marketed for weight loss. The reality is more nuanced.
How GH Affects Body Composition
Growth hormone promotes lipolysis (fat breakdown), particularly from visceral fat stores. It also preserves lean muscle mass during caloric restriction and improves insulin sensitivity (in moderate doses). These effects can produce body composition improvements — less fat, more muscle — without necessarily producing dramatic scale weight changes.
What the Evidence Shows
Tesamorelin (Egrifta): The only FDA-approved GHRH analog. Clinical trials in HIV-associated lipodystrophy showed approximately 15% reduction in trunk fat over 26 weeks. This is specific to visceral adiposity, not general weight loss.
MK-677 (Ibutamoren): Phase II trials in elderly subjects showed increases in lean body mass and modest reductions in body fat percentage, but no significant scale weight reduction. One long-term trial was stopped early due to worsened insulin resistance in some participants — the opposite of what you want for metabolic health.
CJC-1295 + Ipamorelin: No large-scale clinical trials for weight loss exist. Anecdotal reports suggest modest fat loss and improved body composition over 3-6 months of use, but without controlled data, it's impossible to separate real effects from placebo.
The Honest Assessment
GH peptides are not weight loss drugs. They may produce modest improvements in body composition (particularly visceral fat reduction and lean mass preservation) as part of a comprehensive program that includes exercise and nutrition. But anyone expecting GLP-1-level weight loss from growth hormone peptides will be disappointed.
They may have a supportive role alongside other interventions, and they appear in some weight loss protocols as adjuncts — not as primary agents. For more context, see our best peptides for fat loss guide.
AOD-9604: The Disappointing Candidate (Weak Evidence)
AOD-9604 is a modified fragment of human growth hormone (amino acids 177-191) that was specifically developed as an anti-obesity drug. It had a promising start and a disappointing finish.
The Story
Metabolic Pharmaceuticals in Australia developed AOD-9604 in the late 1990s and early 2000s. Phase I and II clinical trials showed some fat loss in obese subjects. The mechanism — stimulating lipolysis without affecting IGF-1 levels or insulin resistance — seemed ideal.
Then the Phase III trial failed. AOD-9604 did not demonstrate statistically significant weight loss over placebo in a large, controlled study. The drug development program was abandoned.
Where It Stands Now
Despite the clinical trial failure, AOD-9604 is still marketed through some peptide therapy clinics and research suppliers. In Australia, it received GRAS (Generally Recognized As Safe) status for use as a food ingredient — but this is not the same as efficacy approval.
The honest assessment: The Phase III trial failure is the most important data point. If AOD-9604 produced meaningful weight loss in a well-controlled study, it would have proceeded to FDA approval. It didn't. Using it as a weight loss agent is going against the evidence, not with it.
For a detailed comparison, see AOD-9604 vs. semaglutide for weight loss.
Other Peptides Marketed for Weight Loss
Several other peptides appear in weight loss discussions:
5-Amino-1MQ: A small-molecule compound (not technically a peptide) that inhibits NNMT (nicotinamide N-methyltransferase), an enzyme involved in fat cell metabolism. Preclinical data shows it prevents diet-induced obesity in mice. No human clinical trials for weight loss exist.
MOTS-c: A mitochondrial-derived peptide that improves insulin sensitivity and exercise capacity in animal models. Preliminary human data is limited. Not proven for weight loss.
Tesofensine: A triple monoamine reuptake inhibitor (not a peptide) that showed impressive weight loss in Phase II trials (approximately 12.8% at highest dose). It's sometimes discussed alongside peptides in weight loss contexts. Phase III trials are ongoing.
BPC-157: Sometimes included in weight loss protocols for its gut-healing properties, particularly for patients with GI issues that complicate weight management. BPC-157 is not a weight loss peptide — it doesn't directly affect appetite or metabolism.
What the Evidence Actually Shows for Each
| Peptide | Weight Loss Evidence | Quality of Evidence | Realistic Expectation |
|---|---|---|---|
| Semaglutide 2.4mg | 14.9% body weight (STEP 1) | Very strong (large RCTs) | 10-17% weight loss over 12-18 months |
| Tirzepatide 15mg | 20.9% body weight (SURMOUNT-1) | Very strong (large RCTs) | 15-22% weight loss over 12-18 months |
| Liraglutide 3.0mg | 8.0% body weight (SCALE) | Strong (large RCTs) | 5-10% weight loss over 12 months |
| Retatrutide (Phase II) | 24.2% body weight | Moderate (Phase II) | TBD pending Phase III |
| Tesamorelin | 15% trunk fat reduction | Moderate (specific indication) | Visceral fat reduction, not total weight loss |
| MK-677 | No significant weight loss | Moderate (Phase II) | Body composition improvement, not scale weight |
| CJC-1295/Ipamorelin | Anecdotal fat loss reports | Weak (no RCTs for weight loss) | Modest, uncertain |
| AOD-9604 | Failed Phase III trial | Negative (failed trial) | Do not expect meaningful weight loss |
Realistic Expectations
What "Works" for Weight Loss Actually Means
In clinical research, "clinically significant weight loss" is typically defined as 5% or more of body weight. By this standard, all GLP-1 agonists "work" — they far exceed this threshold.
But expectations should be calibrated to the specific drug:
- GLP-1 agonists: 10-20% weight loss is a realistic range at optimal doses over 12-18 months. This is genuinely life-changing for many patients.
- Growth hormone peptides: 2-5% body fat reduction and modest body recomposition over 3-6 months. Meaningful for body composition but not dramatic on the scale.
- AOD-9604 and similar: Unproven. Don't expect results that clinical trials couldn't demonstrate.
Weight Loss Is Not Just Weight
GLP-1 agonists produce weight loss that includes both fat and lean mass. The STEP trials showed that approximately 30-40% of weight lost with semaglutide was lean mass (muscle). This is a concern, particularly for older adults, and is driving research into combinations with exercise and resistance training to preserve muscle. See GLP-1 agonists and muscle mass concerns.
Maintenance Matters
Weight lost on peptides tends to return when you stop — particularly with GLP-1 drugs. The STEP 1 extension showed two-thirds weight regain within one year of stopping semaglutide. This means these drugs are likely long-term or lifelong treatments for most users, not short-term courses. For strategies, see what happens when you stop taking peptides.
How GLP-1 Weight Loss Actually Happens
Understanding the mechanism helps set realistic expectations about what these drugs do and don't do.
GLP-1 agonists don't burn fat directly. They don't increase metabolism significantly. They work primarily by changing how hungry you feel and how much food satisfies you:
Appetite suppression: GLP-1 receptors in the hypothalamus reduce hunger signals. Patients consistently describe feeling less driven to eat — not fighting cravings, but simply not having them as intensely.
Delayed gastric emptying: Food stays in the stomach longer, extending the feeling of fullness after meals. A meal that previously left you hungry an hour later now satisfies you for three or four hours.
Altered food reward: Brain imaging studies show that GLP-1 agonists reduce the neural reward response to high-calorie foods. Patients report that their food preferences shift — the pizza that used to be irresistible becomes merely acceptable.
Reduced portion size: As a consequence of the above, people naturally eat less. The weight loss comes from a sustained caloric deficit driven by reduced intake, not from metabolic changes.
This is important context because it means GLP-1 drugs work through behavioral change (eating less) even though the behavioral change is pharmacologically mediated. Exercise, protein intake, and overall diet quality still matter for the type of weight lost and for long-term health outcomes.
The Cost-Benefit Equation
Weight loss peptides span a wide cost range:
- Brand-name tirzepatide: $1,059-$1,300/month → 20% expected weight loss
- Brand-name semaglutide: $1,349-$1,850/month → 15% expected weight loss
- Compounded semaglutide (where available): $149-$399/month → similar efficacy (if quality is equivalent)
- GH peptides (CJC-1295/ipamorelin): $200-$400/month → modest body composition changes
- AOD-9604: $50-$150/month → unproven; clinical trial failed
The cost-per-pound-lost calculation strongly favors proven GLP-1 drugs over unproven alternatives. Spending $400/month on GH peptides that produce 3-5 pounds of fat loss is worse value than spending the same amount on a compounded GLP-1 that produces 20-30 pounds of weight loss.
For a full cost analysis, see how much does peptide therapy cost.
Frequently Asked Questions
What is the most effective peptide for weight loss?
Tirzepatide (Zepbound) at the 15mg dose produces the greatest weight loss of any currently available peptide drug — averaging 20.9% in clinical trials. Retatrutide may exceed this, but it's not yet FDA-approved. Among currently accessible treatments, tirzepatide at maximum tolerated dose is the most effective option.
Can I use peptides for weight loss without exercise?
GLP-1 agonists produce significant weight loss even without exercise programs — the STEP and SURMOUNT trials did not require exercise as part of the protocol. However, exercise — particularly resistance training — is strongly recommended to preserve lean mass during weight loss, improve cardiovascular fitness, and support long-term weight maintenance. The combination of a GLP-1 agonist with regular exercise produces better outcomes than either alone.
Are weight loss peptides safe long-term?
The safety data for GLP-1 agonists is robust. The SELECT trial followed semaglutide users for nearly 4 years with an acceptable safety profile. The most common issues are GI side effects (nausea, vomiting, diarrhea), which are typically manageable and improve over time. See our guide on understanding peptide side effects. For research peptides marketed for weight loss (AOD-9604, 5-Amino-1MQ), long-term safety data doesn't exist.
Will my insurance cover weight loss peptides?
Coverage for anti-obesity medications varies widely. Many commercial insurance plans now cover Wegovy and Zepbound with prior authorization. Medicare currently cannot cover weight loss medications (though legislation may change this). Medicaid coverage varies by state. A diabetes diagnosis dramatically improves insurance coverage for GLP-1 drugs. For details, see insurance coverage for GLP-1 drugs.
How do I choose between semaglutide and tirzepatide?
Both are excellent options. Tirzepatide produces more weight loss on average (20% vs. 15%) but is newer with less long-term data. Semaglutide has the SELECT cardiovascular outcomes trial showing 20% MACE reduction — tirzepatide has not yet matched this. Your doctor will consider your medical history, insurance coverage, side effect tolerance, and treatment goals. See our semaglutide vs. tirzepatide comparison for a detailed breakdown.
The Bottom Line
If you're asking "do peptides work for weight loss?" and you mean GLP-1 receptor agonists — yes, dramatically. Semaglutide and tirzepatide produce 15-21% average weight loss in clinical trials, with cardiovascular benefits and millions of patients treated worldwide. They represent a genuine revolution in obesity treatment.
If you mean growth hormone peptides — they may produce modest body composition changes but are not weight loss drugs and shouldn't be positioned as such.
If you mean AOD-9604 — the evidence says no. The Phase III trial failed.
The responsible approach is clear: if your goal is significant weight loss, the proven peptide options are GLP-1 agonists, accessed through a healthcare provider who can prescribe, monitor, and adjust your treatment. Everything else is either unproven, disproven, or playing a supporting role at best.
References
- Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. NEJM
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. NEJM
- Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med. 2025. NEJM
- Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. NEJM
- ICER. Obesity Evidence Report. October 2025. ICER
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity (Phase II). N Engl J Med. 2023;389(6):514-526. NEJM