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Quick Answer
Semaglutide is the best-evidenced starting point for most people — FDA-approved, widely available through telehealth, and proven to produce ~15% body weight loss in clinical trials. Tirzepatide outperforms it in head-to-head trials (~20–22% body weight) for those who want stronger results. Retatrutide showed up to 24% body weight loss in Phase 2 trials and represents the next generation. Cagrilintide works best as a plateau-breaker stacked on top of existing GLP-1 therapy.
| # | Compound | Best For | Avg. Weight Loss | Availability | Details |
|---|---|---|---|---|---|
| 1 | SemaglutideBest Overall | First-line, strongest evidence base | ~15% body weight (25–65 lbs) | TelehealthResearch | Full guide → |
| 2 | TirzepatideStronger Results | Best head-to-head vs. semaglutide | ~20–22% body weight | TelehealthResearch | Full guide → |
| 3 | RetatrutideMost Aggressive | Highest potential weight loss (Phase 2) | Up to 24% body weight | Research only | Full guide → |
| 4 | CagrilintidePlateau Breaker | Add-on for stalled GLP-1 patients | Additive to existing GLP-1 results | Research only | Full guide → |
15%
avg. body weight lost on semaglutide (STEP trials)
22%
avg. body weight lost on tirzepatide 15mg (SURMOUNT)
24%
max body weight lost on retatrutide (Phase 2)
40%
of weight lost can be lean mass without resistance training
How Weight Loss Peptides Work
The compounds on this page are not stimulants — they don't suppress appetite by flooding the brain with dopamine or norepinephrine. They work by mimicking or amplifying gut hormones that the body already produces to regulate hunger, gastric emptying, and insulin secretion. The result is a durable, physiological reduction in appetite rather than a chemical override that creates tolerance and rebound.
GLP-1 (glucagon-like peptide-1) is a hormone released by intestinal cells after eating. It signals the brain's hypothalamus to reduce hunger, slows gastric emptying (so you feel full longer), and stimulates the pancreas to release insulin in response to glucose. Semaglutide and tirzepatide mimic this hormone — but with much longer half-lives than natural GLP-1, which degrades within minutes.
GIP (glucose-dependent insulinotropic polypeptide) is a second gut hormone that also stimulates insulin secretion and, more recently discovered, plays a role in fat tissue regulation. Tirzepatide uniquely targets both GLP-1 and GIP receptors — this dual mechanism appears to be why it outperforms semaglutide despite similar GLP-1 receptor activity.
Glucagon is a hormone that increases energy expenditure and fat oxidation. Retatrutide adds glucagon receptor agonism to the GLP-1 and GIP effects — making it a triple agonist and explaining its superior weight loss results, as well as introducing unique hepatic effects currently under evaluation in Phase 3.
Amylin is a pancreatic hormone released alongside insulin that suppresses appetite through a completely different neural circuit. Cagrilintide targets amylin receptors — meaning it can provide appetite suppression that compounds with GLP-1 therapy rather than redundantly targeting the same pathway.
#1 Best Overall — Strongest Evidence Base
Semaglutide
Semaglutide is a GLP-1 receptor agonist originally developed by Novo Nordisk for type 2 diabetes (Ozempic) and later approved at higher doses for chronic weight management (Wegovy). It is the most clinically studied weight loss compound available, with data from over 175,000 participants across multiple large randomized trials.
What the trials show
The STEP program — a series of Phase 3 trials — established semaglutide's weight loss profile with precision. STEP 1, the landmark trial in non-diabetic adults with obesity, showed an average 14.9% body weight reduction over 68 weeks compared to 2.4% in the placebo group. In real-world use, this translates to roughly 25–65 lbs depending on starting weight, diet adherence, and exercise habits. Typical trajectory is approximately 1 lb per week in the active phase.
The lean mass concern — what you need to know
Studies show that up to 40% of weight lost on semaglutide can be lean muscle mass without concurrent resistance training and adequate protein intake. This is not unique to semaglutide — it is a feature of rapid, caloric-deficit-driven weight loss generally — but it is clinically significant. Current best practice is to combine GLP-1 therapy with 3+ resistance training sessions per week and a minimum of 1g protein per pound of target body weight daily.
Long-term use and discontinuation
Semaglutide works while you take it. When stopped, approximately 82% of patients regain weight within one year as appetite regulation returns to baseline. Most metabolic physicians now frame it as a long-term intervention rather than a fixed course, similar to how blood pressure medication is managed.
Availability and cost
Semaglutide is available as physician-prescribed compounded semaglutide through telehealth clinics at $115–$200/month — far below the $900–$1,400/month cost of brand-name Wegovy through traditional pharmacy channels. Research vendors also supply it for research purposes without a prescription.
Starting Dose: 0.25mg weekly
Maintenance: 1–2.4mg weekly
Form: Subcutaneous injection (or oral)
Avg. Weight Loss: ~15% body weight
#2 Strongest Results — Outperforms Semaglutide
Tirzepatide
Tirzepatide (Mounjaro for diabetes, Zepbound for obesity) is a dual GIP/GLP-1 receptor agonist developed by Eli Lilly. In every head-to-head comparison with semaglutide, tirzepatide has produced greater weight loss. Most patients who have tried both report tirzepatide as noticeably more effective — with many describing the appetite suppression as more complete, particularly for cravings.
What the trials show
The SURMOUNT-1 trial showed tirzepatide at 15mg achieving an average 22.5% body weight reduction over 72 weeks — roughly 52 lbs in a population with an average starting weight of 230 lbs. Even at 5mg and 10mg, tirzepatide outperformed semaglutide's maximum dose result of 14.9%. Real-world reports reflect 25–60+ lbs of weight loss, with some patients at higher starting weights losing substantially more.
Why it outperforms semaglutide
The GIP receptor component appears to be the differentiating factor. GIP signaling affects fat tissue directly — promoting fat oxidation and potentially reducing the fat cell's ability to store energy — in ways that GLP-1 signaling alone does not. The combination produces synergistic appetite suppression and metabolic effects that explain the larger and faster weight loss observed in trials.
Side effects and muscle loss
GI side effects (nausea, sulfur burps, vomiting) are the most common complaints, especially during dose escalation. They typically resolve within 2–4 weeks at each dose level. The lean mass concern applies equally to tirzepatide — resistance training and protein intake remain essential. Animal studies have raised preliminary questions about bone health with long-term use; Phase 4 human data is ongoing.
Discontinuation risk: Research shows 82% of patients regain weight within one year of stopping tirzepatide. If you start, plan for long-term maintenance. Your physician can advise on maintenance dosing strategies.
Starting Dose: 2.5mg weekly
Maintenance: 5–15mg weekly
Form: Subcutaneous injection
Avg. Weight Loss: ~20–22% body weight
#3 Highest Potential — Phase 3 Trials Active
Retatrutide
Retatrutide is a triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously — making it the most pharmacologically aggressive weight loss peptide in active clinical development. Developed by Eli Lilly, it represents the next step beyond tirzepatide in the GLP-1 drug class evolution.
What the trials show
Phase 2 trial data published in the New England Journal of Medicine in 2023 showed retatrutide at the 12mg dose producing up to 24.2% body weight reduction over 48 weeks — the highest weight loss ever documented in a clinical trial for any pharmacological agent. At lower doses, even the 4mg cohort showed results comparable to semaglutide's maximum dose. Phase 3 trials are currently active.
The glucagon component
Adding glucagon receptor agonism to GLP-1 and GIP activation increases resting energy expenditure and fat oxidation — essentially making the body burn more calories at rest in addition to suppressing appetite. This accounts for the superior results versus tirzepatide. The tradeoff is that glucagon receptor activation also affects liver function and glucose regulation in ways that are still being characterized in the ongoing Phase 3 data.
Current availability
Retatrutide is not FDA-approved and is not available through telehealth clinics. It is available as a research compound through some peptide vendors for research use only. Clinical availability through regulated channels is anticipated in 2026–2027 pending Phase 3 completion.
Trial Dose Range: 1–12mg weekly
Form: Subcutaneous injection
Status: Phase 3 trials active
Max Weight Loss (Phase 2): 24% body weight
#4 Plateau Breaker — Best as an Add-On
Cagrilintide
Cagrilintide is a long-acting amylin receptor agonist developed by Novo Nordisk. Amylin is a hormone co-secreted with insulin by the pancreas — it slows gastric emptying and signals satiety via the brainstem's area postrema, a pathway that is entirely independent from GLP-1's hypothalamic mechanism. This makes cagrilintide uniquely additive to existing GLP-1 therapy rather than redundant.
What it does
Cagrilintide's primary clinical role in 2026 is as a combination partner with semaglutide. The combination — called CagriSema — has demonstrated superior weight loss to either drug alone in Phase 2 trials. Users who have plateaued on semaglutide or tirzepatide report cagrilintide as an effective "plateau breaker" because it adds a second, mechanistically distinct appetite suppression signal on top of the existing GLP-1 effect.
CagriSema combination data
Phase 2 trials of the combined cagrilintide + semaglutide protocol showed outcomes exceeding semaglutide monotherapy at equivalent doses. Novo Nordisk is advancing the fixed-dose combination product through Phase 3, which is expected to represent the next major FDA weight loss approval after tirzepatide.
Who it's for
Cagrilintide makes the most sense for people already on semaglutide or tirzepatide who have hit a weight loss plateau at an optimal dose — or who want to combine satiety mechanisms from the start for more aggressive protocols. It is not the right first choice before trying a GLP-1 agonist alone.
Starting Dose: 0.3mg weekly
Maintenance: 1.2–2.4mg weekly
Form: Subcutaneous injection
Best Use: Combined with semaglutide (CagriSema)
Side-by-Side Comparison
| Factor | Semaglutide | Tirzepatide | Retatrutide | Cagrilintide |
|---|---|---|---|---|
| Receptor targets | GLP-1 | GLP-1 + GIP | GLP-1 + GIP + Glucagon | Amylin |
| Avg. weight loss | ~15% | ~20–22% | Up to 24% (Phase 2) | Additive to GLP-1 |
| FDA approved | Yes (Wegovy) | Yes (Zepbound) | No — Phase 3 | No — Phase 3 |
| Telehealth available | Yes | Yes | Research only | Research only |
| Starting dose | 0.25mg/week | 2.5mg/week | 1mg/week | 0.3mg/week |
| Injection frequency | Weekly | Weekly | Weekly | Weekly |
| Best as | First-line choice | Upgrade from sema | Aggressive protocol | Add-on / plateau fix |
| Evidence depth | Extensive (10+ yrs) | Strong (3+ yrs) | Early (Phase 2/3) | Early (Phase 2/3) |
What to Expect — A Realistic Timeline
Weight loss peptides work on a predictable progression. Understanding the timeline helps calibrate expectations and avoid abandoning a protocol too early.
- Weeks 1–4: Dose titration phase. Nausea and GI effects are most common here and typically resolve by week 4–6. Modest appetite reduction. Some early water weight loss.
- Weeks 4–12: Appetite suppression becomes consistent and noticeable. Fat loss begins. 1–2 lbs per week typical trajectory. Most people feel the "food noise" — constant background hunger thoughts — begin to quiet.
- Weeks 12–24: Body composition changes visible. Energy improves as excess weight comes off. Metabolic markers (blood sugar, lipids) typically improve. May need dose optimization.
- 6+ months: Some patients reach a plateau. This is normal and usually addressable with dose adjustment, protocol modification, or addition of a second compound like cagrilintide.
The most important non-pharmacological factors are resistance training (to preserve lean mass) and protein intake. These are not optional additions — they directly determine the quality of the weight loss.
How to Choose the Right Compound
Start with semaglutide if you want the most established option with the deepest safety data, physician access through telehealth, and proven results. It is the right first choice for the vast majority of people.
Start with tirzepatide if you want the strongest currently-approved option, can access it through telehealth or accept the higher cost, and prefer maximizing results over familiarity.
Consider retatrutide only if you have exhausted standard options, understand it is research-grade and not FDA-approved, and want to pursue the most aggressive available protocol.
Add cagrilintide if you are already on semaglutide or tirzepatide, have plateaued, and want to add a mechanistically distinct second signal rather than simply increasing your GLP-1 dose.
Where to Get Weight Loss Peptides
Telehealth is the recommended route for semaglutide and tirzepatide — physician oversight, lab monitoring, and dose management are genuinely valuable for these compounds given the importance of preserving lean mass and managing side effects properly.
- Marek Health — $166/mo, prescribes semaglutide, tirzepatide, and compounded combinations. Read review →
- Limitless Alt Med — $115–$275/mo depending on protocol. Read review →
- Maximus — $199/mo. Read review →
- NextGenPeps — Research vendor; semaglutide, tirzepatide, retatrutide, cagrilintide available without prescription for research use. Code 3LUIZH10 for a discount.
Frequently Asked Questions
What is the best peptide for weight loss?
Semaglutide is the best-evidenced starting point — FDA-approved and proven to produce ~15% body weight loss in clinical trials. Tirzepatide outperforms it in head-to-head data (~20–22%) and is the stronger option if you can access it. Retatrutide showed up to 24% body weight loss in Phase 2 trials but is not yet FDA-approved.
How much weight can you lose on semaglutide?
The STEP 1 trial showed an average of 14.9% body weight reduction over 68 weeks. In real-world use, patients typically lose 25–65 lbs depending on starting weight, adherence, and whether resistance training is combined. Approximately 1 lb per week is a typical active-phase trajectory.
Is tirzepatide better than semaglutide for weight loss?
Yes, in head-to-head comparisons. The SURMOUNT trials showed tirzepatide at 15mg producing ~22.5% body weight reduction versus semaglutide's ~15%. Most patients who have used both report tirzepatide as more effective, particularly for reducing cravings. The tradeoff is higher cost and slightly different side effect profile.
Do you regain weight after stopping GLP-1 peptides?
Yes. Research shows approximately 82% of patients regain weight within one year of stopping. GLP-1 agonists suppress appetite neurologically — when the drug is removed, the appetite signal returns to baseline. Most physicians now frame GLP-1 therapy as a long-term or lifelong intervention rather than a fixed course.
Will I lose muscle on weight loss peptides?
Potentially — studies show up to 40% of weight lost on GLP-1 agonists can be lean mass without adequate resistance training and protein intake. Current clinical guidance recommends combining GLP-1 therapy with 3+ resistance sessions per week and at least 1g protein per pound of target body weight daily.
What is cagrilintide and who should use it?
Cagrilintide is a long-acting amylin receptor agonist that works through a completely different mechanism than GLP-1 drugs. It is most useful as an add-on for people who have plateaued on semaglutide or tirzepatide. The combined CagriSema protocol has shown superior results to either drug alone in Phase 2 trials.
How do I get a prescription for weight loss peptides?
Telehealth clinics including Marek Health, Limitless Alt Med, and Maximus prescribe compounded semaglutide and tirzepatide online. Complete a medical intake, submit bloodwork, and receive a prescription delivered to a compounding pharmacy — typically within 1–2 weeks.
How much does semaglutide cost through telehealth?
Compounded semaglutide through telehealth clinics typically costs $115–$200/month — significantly less than brand-name Wegovy ($900–$1,400/month without insurance). Research vendor pricing is lower still, but those products are for research use only and lack physician oversight.
What is retatrutide and how does it compare?
Retatrutide is a triple receptor agonist targeting GLP-1, GIP, and glucagon receptors. Phase 2 trials showed up to 24% body weight reduction — exceeding both semaglutide and tirzepatide. It is currently in Phase 3 trials and not yet FDA-approved. It is available as a research compound from some vendors.
Want to compare clinics side by side?
See all telehealth clinics that prescribe semaglutide and tirzepatide — pricing, lab requirements, and protocol differences in one table.
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