“Peptides for weight loss” covers two very different groups. The first is the incretin family (semaglutide, tirzepatide, and now retatrutide and cagrilintide), which has phase 3 trials in tens of thousands of people and average losses of 15% to 28% of body weight. The second is everything else sold online for fat loss (AOD-9604, MOTS-c, CJC-1295, ipamorelin and others), where the human evidence for weight loss is thin, negative, or absent.
That gap is the most important fact in this whole topic. Below, every commonly discussed compound is ranked by the quality of its human evidence, with what was actually measured, the Canadian regulatory status, and where each one fits in research.
The ranking at a glance
| Compound | Mechanism | Best human evidence | Average weight loss in trials | Approved in Canada? |
|---|---|---|---|---|
| Retatrutide | GLP-1 + GIP + glucagon agonist | Five phase 3 trials | Up to 28.3% at 80 weeks | No (FDA filing planned 2027) |
| Tirzepatide | GLP-1 + GIP agonist | Multiple phase 3 trials | About 21% at 72 weeks (top dose) | Yes (Mounjaro, Zepbound) |
| CagriSema | Amylin + GLP-1 | Phase 3 (REDEFINE) | About 20% at 68 weeks | No (filed in the US) |
| Semaglutide | GLP-1 agonist | Multiple phase 3 trials | About 15% at 68 weeks | Yes (Wegovy, Ozempic, generics) |
| Liraglutide | GLP-1 agonist | Phase 3 (SCALE) | About 8% at 56 weeks | Yes (Saxenda) |
| Tesamorelin | GHRH analogue | Phase 3 in HIV lipodystrophy | Visceral fat about −15%; little change in weight | Yes, for HIV abdominal fat only |
| MOTS-c | Mitochondrial-derived peptide | Mouse studies; small early human study of an analogue | Not established in humans | No |
| AOD-9604 | GH fragment 176–191 | Phase 2b, about 500 people | Not different from placebo | No |
| CJC-1295 / ipamorelin | GH secretagogues | Small hormone studies; no obesity trials | Not established | No |
How peptides can affect body weight
There are only a handful of biological levers a compound can pull to change body weight, and it helps to know which lever each peptide is supposed to use:
- Eat less: appetite and fullness signalling in the brain and gut. This is where GLP-1, GIP and amylin act, and it is by far the most powerful lever found so far.
- Burn more: energy expenditure. Glucagon receptor activity (retatrutide) and, in mice, MOTS-c appear to raise it.
- Move fat around: break down stored fat (lipolysis) or shift where it’s stored. Growth hormone and its fragments (tesamorelin, AOD-9604) act here. Lipolysis on its own doesn’t mean weight loss: the released fat has to be burned, not re-stored.
- Absorb less: not a significant peptide mechanism; this is the territory of drugs like orlistat.
The reason the incretin drugs dominate is simple: changing how much people eat, consistently, for months, moves weight far more than any metabolic tweak does.
Tier 1: incretin drugs with phase 3 data
These are the compounds with large, randomized, placebo-controlled trials published in major journals. They are the reason “peptides for weight loss” became a search term at all.
Semaglutide
Semaglutide is a GLP-1 receptor agonist with a fatty-acid side chain that lets it be given once a week. In STEP 1 (NEJM, 2021), 1,961 adults with obesity lost an average of 14.9% of body weight over 68 weeks on 2.4 mg weekly, versus 2.4% on placebo. It is sold in Canada as Ozempic (diabetes) and Wegovy (weight management), and generic semaglutide arrived in Canada in 2026 after patent protection lapsed here.
Semaglutide is the reference compound for the whole field: well characterized, with years of safety data, including the cardiovascular outcome benefits seen in the SELECT trial.
Tirzepatide
Tirzepatide activates both GLP-1 and GIP receptors. In SURMOUNT-1 (NEJM, 2022), 2,539 adults with obesity lost an average of 20.9% at 72 weeks on the highest dose (15 mg), versus 3.1% on placebo. In Canada it’s sold as Mounjaro (diabetes) and, since May 2025, Zepbound (weight management).
The GIP component was originally expected to hurt weight loss, because GIP promotes fat storage in some contexts. Instead, the combination outperformed GLP-1 alone, a result researchers are still unpicking. See Tirzepatide research in Canada and tirzepatide side effects.
Retatrutide
Retatrutide adds glucagon receptor activity to GLP-1 and GIP. In TRIUMPH-1, average weight loss reached 28.3% at 80 weeks on the top dose, and 30.3% at 104 weeks in an extension, the largest figures reported for any obesity drug. The trade-offs are more gastrointestinal side effects at high doses and a new signal of dysesthesia (unusual skin sensations).
It is not approved anywhere yet; Lilly plans to file with the FDA in early 2027. Full details: Retatrutide phase 3 results and Retatrutide in Canada.
Cagrilintide and CagriSema
Cagrilintide is a long-acting analogue of amylin, a hormone released with insulin that signals fullness through a different pathway from GLP-1. On its own, it produced around 10% weight loss in a phase 2 trial. Combined with semaglutide as CagriSema, the REDEFINE 1 trial reported about 20% average weight loss at 68 weeks. Novo Nordisk filed CagriSema with the FDA in December 2025.
Amylin analogues are attractive to researchers because they may produce weight loss with a different side-effect profile and potentially better preservation of lean mass. More in our cagrilintide research guide.
Each step up the incretin ladder (one receptor, two receptors, three receptors, or adding amylin) has added roughly 5 to 7 percentage points of average weight loss. Nothing outside this family has come close in a controlled human trial.
Tier 2: real human data, narrow use
Tesamorelin
Tesamorelin is the most interesting “non-incretin” weight peptide, because it has genuine phase 3 data. It is a stabilized analogue of growth-hormone-releasing hormone (GHRH) that prompts the pituitary to release more of the body’s own growth hormone.
In the trials that led to its approval (as Egrifta), people living with HIV who had excess abdominal fat saw visceral fat fall by about 15% over 26 weeks while it stayed roughly flat on placebo, and body weight barely changed. It was approved by the FDA in 2010 and by Health Canada in 2014, for that indication only. A later trial found it also reduced liver fat in the same population.
Tesamorelin is therefore a fat-redistribution compound, not a weight-loss drug. Its value in research is as a tool for studying visceral fat and the GH axis specifically. Full guide: What is tesamorelin?
Tier 3: promising animal data, little human data
MOTS-c
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, discovered in 2015. In that first paper (Cell Metabolism), MOTS-c prevented diet-induced obesity and insulin resistance in mice. A 2021 Nature Communications study showed it improved physical capacity in older mice and that its levels rise with exercise in humans.
Human evidence for weight loss is essentially absent. CohBar developed an analogue, CB4211, which showed modest reductions in liver fat and some glucose markers in a small early study in 2021 but was not taken further. In July 2026, an FDA advisory committee voted 7–5 to recommend MOTS-c for the US compounding bulk list. That vote concerned whether pharmacists may compound it, not whether it works. Full guide: What is MOTS-c?
Tier 4: tested in humans and failed, or never tested
AOD-9604
AOD-9604 is the cautionary tale of the category. It is a modified fragment of the tail end of human growth hormone (the 176–191 region), designed to keep GH’s fat-burning effect without its effects on growth or blood sugar. It worked in obese mice.
It then went through six human trials with roughly 900 participants. Safety looked good, comparable to placebo. But in the largest trial, a 24-week phase 2b study, weight loss wasn’t significantly different from placebo, and the developer abandoned it for obesity in 2007. It is still heavily marketed online for fat loss, largely on the strength of the mouse data. Full story: What is AOD-9604?
CJC-1295, ipamorelin and GH secretagogues
CJC-1295 (a GHRH analogue) and ipamorelin (a ghrelin-receptor agonist) both raise growth hormone release, and are often sold together for “body recomposition”. The logic is borrowed from tesamorelin: more GH, less visceral fat.
The evidence doesn’t follow the logic. CJC-1295’s human data comes from small studies measuring hormone levels in healthy adults; ipamorelin’s human trials were for post-surgical gut recovery and did not meet their goals. Neither has been tested as an obesity treatment. Raising GH does mobilize fat, but growth hormone also raises blood sugar and causes fluid retention, which is part of why GH itself was never developed as an obesity drug. Background: CJC-1295 and ipamorelin.
Other compounds you’ll see mentioned
| Compound | Claim | Reality |
|---|---|---|
| HGH fragment 176–191 | “Fat-burning fragment” | Essentially the same story as AOD-9604 |
| 5-Amino-1MQ | “Fat cell shrinker” | A small molecule, not a peptide; mouse data only |
| SS-31 (elamipretide) | “Mitochondrial fat loss” | FDA-approved in 2025 for Barth syndrome; no weight-loss data |
| NAD+ | “Metabolism booster” | Not a peptide; human weight data are null |
| Melanotan II | “Appetite suppressant” | Acts on melanocortin receptors; not studied for weight; serious safety concerns |
| Kisspeptin | Occasionally linked to metabolism | Reproductive hormone research; no weight data |
Side effects across the incretin class
Because the tier 1 compounds share a mechanism, they share most of their side effects. The pattern in trials is consistent:
| Side effect | How common | Notes |
|---|---|---|
| Nausea | Very common (roughly 20–45% in trials) | Mostly during dose escalation; fades for most people |
| Diarrhea, constipation, vomiting | Common | Main reason people stop treatment in trials |
| Gallbladder problems | Uncommon, but increased | Linked to rapid weight loss in general |
| Pancreatitis | Rare | A labelled warning across the class |
| Heart rate increase | Small average increase | A few beats per minute; more noticeable with glucagon activity |
| Hair shedding | Reported | Usually linked to rapid weight loss rather than the drug itself |
| Dysesthesia | Seen with retatrutide | A new signal not prominent with the older drugs |
For the deeper dives, see tirzepatide side effects, Is retatrutide safe? and hair loss on GLP-1 drugs. The tier 3 and 4 compounds mostly lack the large trials needed to describe side effects with any confidence. With AOD-9604, the large trials found effects similar to placebo, but with no weight loss to weigh them against.
Pills vs injections: where peptides end and small molecules begin
Peptides are broken down by stomach acid and digestive enzymes, which is why most are injected. Two developments are changing that picture:
- Oral semaglutide. Semaglutide can be absorbed from a tablet when it is co-formulated with an absorption enhancer (SNAC). It was first sold as Rybelsus for diabetes. A higher-dose oral semaglutide for weight management (the “Wegovy pill”) was approved by the FDA in December 2025.
- Orforglipron. Lilly’s orforglipron activates the GLP-1 receptor but is not a peptide. It is a small molecule that survives digestion without special formulation. The FDA approved it for weight management in April 2026 as Foundayo.
This matters for the “peptides for weight loss” question, because the next generation of the most effective drugs may not be peptides at all. The receptor is what counts, not the molecule’s chemical class.
What’s coming next
The pipeline is crowded. The compounds most likely to matter over the next few years:
| Compound | Developer | Mechanism | Stage |
|---|---|---|---|
| Retatrutide | Eli Lilly | GLP-1 + GIP + glucagon | FDA filing planned Q1 2027 |
| CagriSema | Novo Nordisk | Amylin + GLP-1 (two molecules) | Filed with the FDA, December 2025 |
| Amycretin | Novo Nordisk | Amylin + GLP-1 in one molecule | Late-stage development |
| Survodutide | Boehringer Ingelheim | GLP-1 + glucagon | Phase 3 |
| MariTide (maridebart cafraglutide) | Amgen | Antibody–peptide conjugate, monthly dosing | Phase 3 |
Two themes run through this list: adding amylin or glucagon activity to GLP-1, and dosing less often. We cover the full field in The next weight loss drugs after Ozempic.
The muscle problem
Every effective weight-loss compound causes some loss of lean mass, because when you lose weight you lose some muscle along with fat. In the DXA sub-studies of STEP 1 and SURMOUNT-1, roughly a quarter to two-fifths of the weight lost was lean mass. That proportion is similar to diet-induced weight loss, but the absolute amount is larger because the total weight lost is larger.
This has created a second research wave: compounds meant to preserve muscle during incretin-driven weight loss. Candidates include myostatin and activin pathway antibodies (bimagrumab and others), as well as amylin analogues, which in early data may spare lean mass better. Resistance training and adequate protein remain the only proven tools. We go through the numbers in Muscle loss on GLP-1 drugs.
The regain problem
When the STEP 1 participants stopped semaglutide, they regained about two-thirds of the weight they had lost within a year, and most of the cardiometabolic improvements went with it. The same pattern has appeared with tirzepatide.
Obesity behaves like a chronic condition: the drugs manage it while taken. For research, this has raised a set of open questions: whether slower tapering helps, whether some compounds produce more durable changes, and how the body’s set point adapts. None of the tier 3 or tier 4 compounds have data that address them.
What’s actually available in Canada
For people, the legitimate options for medical weight management in Canada are prescription drugs, prescribed by a clinician:
| Drug | Type | Status in Canada |
|---|---|---|
| Wegovy (semaglutide) | Weekly injection | Approved for weight management |
| Generic semaglutide | Weekly injection | Available since 2026 |
| Zepbound (tirzepatide) | Weekly injection | Approved for weight management (since 2025) |
| Saxenda (liraglutide) | Daily injection | Approved for weight management |
| Contrave (naltrexone-bupropion) | Tablet | Approved; not a peptide |
| Orlistat | Capsule | Approved; not a peptide |
Costs and coverage are covered in Weight loss injections in Canada. Everything else on this page that is not on that table is either investigational or a research compound, and Health Canada’s April 2026 advisory specifically warned Canadians against injecting peptides bought online.
TrueLabs sells research compounds for in vitro and laboratory use. Nothing on this page is a recommendation to use any compound for personal weight loss. If that’s your goal, the approved drugs above, prescribed and monitored by a clinician, are the evidence-based route.
For researchers: choosing a compound
If you are designing metabolic research, the compound should follow the question. A few common designs:
| Research question | Compounds |
|---|---|
| Incremental contribution of each incretin receptor | Semaglutide → tirzepatide → retatrutide |
| Amylin vs GLP-1 pathways, alone and combined | Cagrilintide with and without a GLP-1 agonist |
| Visceral fat and the GH axis | Tesamorelin |
| Mitochondrial signalling, exercise mimetics | MOTS-c, SS-31 |
| Lipolysis without IGF-1 effects (a replication question) | AOD-9604 |
Whatever the compound, identity and purity verification matters more for the long incretin peptides than for short ones. See How to read a peptide COA.
Browse TrueLabs research compounds →
Weight loss is not the only outcome that matters
A percentage on a scale is the easiest number to compare, but it’s rarely the reason a drug matters medically. The incretin drugs have built their case on harder outcomes too:
- Heart attacks and strokes. In the SELECT trial, semaglutide reduced major cardiovascular events by about 20% in people with established heart disease and overweight, without diabetes.
- Diabetes prevention. Long-term tirzepatide data showed a large reduction in progression from prediabetes to type 2 diabetes.
- Liver disease. Semaglutide (as Wegovy) received conditional approval in Canada in December 2025 for MASH, an advanced form of fatty liver disease. Retatrutide normalized liver fat in most participants on higher doses in a phase 2a sub-study. See fatty liver treatment in Canada.
- Joint pain. Semaglutide and retatrutide both reduced knee osteoarthritis pain in dedicated trials, largely by reducing load on the joint.
- Sleep apnea. Tirzepatide is approved in the US for obstructive sleep apnea with obesity.
None of the tier 3 or tier 4 compounds have outcome data of any kind in humans. That’s the clearest way to see the distance between the two groups.
How to read weight-loss peptide claims online
A few questions will sort most claims in seconds:
- Was it tested in humans? Mouse obesity models respond to many things that do nothing in people. AOD-9604 is the textbook example.
- Was there a placebo group? People enrolled in any weight-loss study tend to lose some weight, so uncontrolled results overstate the effect.
- How many people, for how long? Twelve people for eight weeks isn’t the same evidence as 2,000 people for 72 weeks.
- What was measured? “Increased fat oxidation” or “improved body composition” are not weight loss.
- Who is making the claim? A seller’s product page isn’t a source; a journal article is.
FAQ
Tap a question to reveal the answer.
What is the most effective peptide for weight loss?
In controlled human trials, retatrutide has produced the largest average weight loss (28.3% at 80 weeks in TRIUMPH-1), but it is not approved yet. Among approved drugs, tirzepatide produces more average weight loss than semaglutide.
Do peptides like AOD-9604 or CJC-1295 cause weight loss?
Not according to controlled human evidence. AOD-9604 did not beat placebo for weight loss in its largest trial, and CJC-1295 and ipamorelin have never been tested as obesity treatments.
Is semaglutide a peptide?
Yes. Semaglutide, tirzepatide, retatrutide and cagrilintide are all peptides: chains of amino acids modified to last longer in the body. Most are given by injection because peptides are broken down in the gut, though an oral form of semaglutide exists.
Is MOTS-c good for fat loss?
MOTS-c prevented diet-induced obesity in mice, but there are no controlled human weight-loss trials. It remains a research compound.
Which weight-loss peptides are approved in Canada?
Semaglutide (Wegovy and generics), tirzepatide (Zepbound) and liraglutide (Saxenda) are approved for weight management. Tesamorelin is approved, but only for excess abdominal fat in people living with HIV.
Why do people regain weight after stopping GLP-1 drugs?
The drugs reduce appetite while they are taken. When they stop, appetite signalling returns to baseline. In the STEP 1 extension, participants regained about two-thirds of the lost weight within a year of stopping semaglutide.
Do weight-loss peptides cause muscle loss?
All effective weight loss includes some lean mass loss. With semaglutide and tirzepatide, roughly a quarter to two-fifths of weight lost in trial sub-studies was lean mass, similar to diet-induced weight loss.
Are weight-loss peptides bought online safe?
Health Canada warned in April 2026 that peptides bought online for injection have not been assessed for safety, effectiveness or quality and may contain the wrong ingredient, the wrong amount or contaminants. Approved drugs, prescribed by a clinician, are the safe route for people.
Related reading
- Retatrutide vs tirzepatide vs semaglutide
- The next weight loss drugs after Ozempic
- Weight loss injections in Canada
- Muscle loss on GLP-1 drugs
- Loose skin after weight loss
References
- Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384:989–1002. PubMed
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022;387:205–216. PubMed
- Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE). N Engl J Med. 2015;373:11–22. PubMed
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389:514–526. PubMed
- Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med. 2025. DOI
- Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357:2359–2370. PubMed
- Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21:443–454. PubMed
- Heffernan M, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice. Endocrinology. 2001;142:5182–5189. PubMed
- Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24:1553–1564. PubMed
- AJMC. Retatrutide achieves up to 30.3% average weight loss in phase 3 TRIUMPH-1 trial. May 2026. AJMC
- Health Canada. Think twice before injecting peptides bought online. Public advisory, April 9, 2026. Health Canada
This article summarizes published research for information only and is not medical advice. Doses mentioned are those used in clinical trials. TrueLabs research compounds are sold for in vitro and laboratory research use only and are not intended for human or veterinary use.