Skip to content
thispeptide

Peptides for Weight Loss: What the Evidence Shows Beyond Semaglutide and Tirzepatide

The peptides with real weight-loss evidence are close relatives of the GLP-1 drugs. Several others sold for fat loss have little or no human data behind them.

Article type
Evidence
Sources
8
Reading
7 min
By Molly WardPublished

If you are looking past semaglutide and tirzepatide, here is the short answer. The peptides with real weight-loss evidence are close relatives of those two. They mimic gut hormones, and each was tested in a large randomized trial. Several others sold for fat loss have little or no human data behind them.

A peptide is a short chain of amino acids, and what that means in practice is covered separately. Being a peptide says nothing about whether a molecule works. The trial record does. For the goal as a whole, start at the weight goal page.

Liraglutide: the older daily option

Liraglutide is a once-daily GLP-1 drug. The SCALE trial gave 3.0 mg a day or placebo to 3,731 adults without type 2 diabetes for 56 weeks [1]. Everyone also got lifestyle counseling.

People on liraglutide lost a mean of 8.4 kg. People on placebo lost 2.8 kg. At least 5% of body weight was lost by 63.2% on the drug and 27.1% on placebo. The most common side effects were mild or moderate nausea and diarrhea.

Retatrutide: three receptors at once

Retatrutide acts on three hormone receptors: GLP-1, GIP and glucagon. A phase 2 trial enrolled 338 adults with obesity for 48 weeks [2]. On the 12 mg dose, mean weight change was −24.2%, against −2.1% on placebo.

That is one mid-stage trial, not a full phase 3 program. Side effects were mostly stomach and bowel symptoms and rose with dose. Heart rate went up with dose, peaked at 24 weeks, then declined.

CagriSema: two peptides in one shot

CagriSema pairs semaglutide 2.4 mg with cagrilintide 2.4 mg, a peptide that mimics the hormone amylin. REDEFINE 1 randomized 3,417 adults without diabetes for 68 weeks [3].

Mean weight change was −20.4% on the combination and −3.0% on placebo. Stomach and bowel side effects hit 79.6% on the combination and 39.9% on placebo. Most were short-lived and mild to moderate.

Tesamorelin: belly fat, not body weight

Tesamorelin comes up in weight-loss searches because it reduces fat around the organs. In a trial of 412 people with HIV, that deep belly fat fell 15.2% on tesamorelin over 26 weeks and rose 5.0% on placebo [4].

Its FDA label is blunt about the limit. It says the drug is “not indicated for weight loss management as it has a weight neutral effect” [5]. The tesamorelin trials are covered in full elsewhere.

AOD-9604 and MOTS-c: almost no human data

These two are sold online for fat loss. The FDA’s own summary of what is known about them is stark [6].

For AOD-9604, the FDA says it has “no, or only limited, safety-related information.” It also notes serious adverse events that may be linked to it, though cause is unclear. For MOTS-c, the FDA says it has not found any human exposure data at all. The nominations to compound both of them were withdrawn.

MOTS-c came back for a July 2026 advisory meeting, reviewed for obesity. FDA’s briefing found no clinical studies or human exposure data by any route [7]. The committee still voted to recommend listing it [8]. That vote is not binding; listing would still require FDA rulemaking. The legal picture explains what that means.

What to take from this

The trade-off is simple to state. The peptides with the most weight lost also have the most side-effect data, because they were tested in thousands of people. The ones with no trials have no side-effect data either. That is a reason for caution, not a sign of safety.

If you are weighing options, ask a prescriber which of these has a trial in people like you. Then ask what the trial dose and length were.

Frequently asked questions

Which peptides have the strongest evidence for weight loss?
The gut-hormone peptides tested in large randomized trials. Liraglutide 3.0 mg produced 8.4 kg of loss against 2.8 kg on placebo over 56 weeks. Retatrutide and CagriSema produced mean losses of about 20% or more in their trials.
Does tesamorelin cause weight loss?
Its FDA label says it is not indicated for weight loss management because it has a weight neutral effect. It reduces the deep belly fat around the organs in people with HIV.
Is there human evidence for AOD-9604 or MOTS-c?
Very little. The FDA says it has no, or only limited, safety information for AOD-9604, and has not identified any human exposure data for MOTS-c.
Can these trial results be compared with each other?
Not directly. Each comes from a different trial with different people, doses and durations. The only direct comparison in this family is tirzepatide against semaglutide.

Sources

8 cited
  1. 1Pi-Sunyer X, Astrup A, Fujioka K, et al. (2015). A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management New England Journal of Medicine. PMID 26132939
  2. 2Jastreboff AM, Kaplan LM, Frías JP, et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial New England Journal of Medicine. PMID 37366315
  3. 3Garvey WT, Blüher M, Osorto Contreras CK, et al. (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity New England Journal of Medicine. PMID 40544433
  4. 4Falutz J, Allas S, Blot K, et al. (2007). Metabolic effects of a growth hormone-releasing factor in patients with HIV New England Journal of Medicine. PMID 18057338
  5. 5Theratechnologies Inc. (2026). EGRIFTA WR (tesamorelin) for injection, prescribing information DailyMed, U.S. National Library of Medicine. Source
  6. 6U.S. Food and Drug Administration (2026). Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks FDA, Human Drug Compounding. Source
  7. 7U.S. Food and Drug Administration (2026). FDA Briefing Document for MOTS-c-Related Bulk Drug Substances, Pharmacy Compounding Advisory Committee, July 23-24, 2026 FDA. Source
  8. 8National Community Pharmacists Association (2026). FDA advisory committee nominates six peptides for pharmacies to compound NCPA. Source

More on weight