Peptides for Weight Loss: What the Evidence Shows

Semaglutide (Wegovy). Approved as a once-weekly subcutaneous injection for chronic weight management in adults with a BMI of 30 or above, or 27 or above with at least one weight-related comorbid condition. In the pivotal 68-week trial described in the label (Study 1, n=1,306 on semaglutide vs 655 on placebo), mean body weight changed by -14.9% with semaglutide 2.4 mg versus -2.4% with placebo. In the same study, 83.5% of the semaglutide group lost at least 5% of body weight versus 31.1% on placebo, and 47.9% lost at least 15% versus 4.8%. A separate oral semaglutide tablet for weight management was approved under NDA 218316 on 22 December 2025.

Tirzepatide (Zepbound). A dual GIP and GLP-1 receptor agonist, approved 8 November 2023. Its pivotal 72-week trial reported mean weight change of -15.0% at 5 mg, -19.5% at 10 mg, and -20.9% at 15 mg, against -3.1% on placebo, with roughly 630 participants per arm. The proportion losing at least 15% of body weight ran from 48.0% at 5 mg to 70.6% at 15 mg, versus 8.8% on placebo.

Liraglutide (Saxenda). The oldest of the group, approved 23 December 2014. It is a daily injection rather than weekly, and its reported weight loss is substantially smaller than the newer agents. It is still on the market and still prescribed, but it has been largely displaced clinically.

Setmelanotide (Imcivree). Approved 25 November 2020, this one is not a general obesity drug. It targets the melanocortin-4 receptor pathway and is indicated for obesity caused by specific confirmed genetic defects. Genetic testing gates the prescription.

For per-compound breakdowns of what each label and trial actually specifies, see our pages on semaglutide dosage and tirzepatide dosage.

Both leading approved peptides are labelled with a mandatory step-up, and this is the part most summaries skip.

Wegovy's label starts at 0.25 mg once weekly for four weeks, then increases at four-week intervals until the 2.4 mg maintenance dose is reached. That is a 16-week ramp before anyone is on the dose that produced the trial results.

Zepbound's label starts at 2.5 mg once weekly, explicitly stating that 2.5 mg is for initiation and is not intended for chronic weight management. After four weeks the dose increases to 5 mg, and further increases happen in 2.5 mg increments after at least four weeks at the current dose, to a maintenance dose of 5, 10, or 15 mg and a maximum of 15 mg.

The published headline percentages come from people who completed those ramps. A four-week snapshot at a starting dose is not a preview of the 68- or 72-week number. Which dose a given person should be on, and whether escalation should proceed at all, is a prescriber's decision made on tolerability and response, not something a chart can settle.

Retatrutide is the compound generating the most search traffic among unapproved options, and unlike most research-chemical peptides it has genuine Phase 3 data. It is a triple agonist at GIP, GLP-1, and glucagon receptors.

In TRIUMPH-1 (NCT05929066), a Phase 3 trial that randomised 2,339 participants across 4 mg, 9 mg, 12 mg, and placebo arms, topline results announced in May 2026 reported mean weight change at 80 weeks of -17.6% (4 mg), -23.7% (9 mg), -25.0% (12 mg), and -3.9% (placebo) under the treatment-regimen estimand. Under the efficacy estimand, which models what would have happened had everyone stayed on treatment, the same arms read -19.0%, -25.9%, -28.3%, and -2.2%. A pre-specified extension of 532 participants with BMI 35 or above continued to 104 weeks and reached up to -30.3%.

Two caveats belong next to those numbers. First, they are topline company results; the full peer-reviewed publication had not appeared at the time of writing. Second, and more practically, Lilly's own statement is that retatrutide is legally available only to participants in its clinical trials. Anything else circulating under that name did not come from the trial supply chain. See our retatrutide dosage page for what the trial protocol itself specifies.

Cagrilintide plus semaglutide (CagriSema) is another combination under FDA review following a New Drug Application submitted in December 2025. It was not approved at the time of writing.

This is a genuine source of confusion, and it changes what the dosing maths looks like.

Foundayo (orforglipron) was approved on 1 April 2026 for weight management. It is a GLP-1 receptor partial agonist, but it is a non-peptide small molecule taken as a once-daily tablet. The FDA describes a starting dose of 0.8 mg, increasing to 2.5 mg after at least 30 days, then 5.5 mg, with possible further steps to 9 mg, 14.5 mg, or 17.2 mg. There is no vial, no reconstitution, and no syringe involved.

Tesofensine, which appears on plenty of "best peptides for weight loss" lists, is a triple monoamine reuptake inhibitor. It is also not a peptide, and it has no FDA approval for obesity; ClinicalTrials.gov lists a completed Phase 2 obesity study but no Phase 3 obesity programme.

If a list mixes these in with semaglutide without flagging the difference, treat the rest of the list with suspicion.

Two names come up constantly and deserve a direct answer.

AOD-9604 is a fragment of human growth hormone marketed heavily for fat loss. Searching ClinicalTrials.gov for AOD-9604 returns zero registered studies. It appears in older review articles as a compound that was in development, but there is no registered trial record supporting a weight loss claim, and it has no FDA approval. Our AOD-9604 dosage page documents what vendors and early literature describe, which is not the same as evidence of effect.

5-Amino-1MQ likewise returns zero registered studies on ClinicalTrials.gov. Published work on it is preclinical.

The same is true of most growth-hormone-secretagogue stacks sold for "fat loss." Absence of a registered trial is not proof a compound does nothing, but it does mean nobody can tell you an effect size, and any percentage figure you see quoted for these compounds was not measured in a controlled human trial.

Here is a distinction the dosing conversation routinely gets wrong.

The approved products are not reconstituted. Wegovy, Zepbound, and Saxenda ship as pre-filled pens containing solution. There is no powder, no bacteriostatic water, and no unit conversion for the patient to perform. The pen delivers the labelled dose.

Reconstitution maths applies to lyophilised powder in vials, which is how unapproved research compounds are supplied. The arithmetic itself is simple and worth understanding regardless:

• A U-100 insulin syringe holds 100 units per 1 mL. Units are a volume marking, not a mass.
• Concentration equals total peptide mass divided by the volume of diluent added. Reconstituting a 10 mg vial with 2 mL of bacteriostatic water gives 5 mg/mL.
• Volume needed equals target mass divided by concentration. At 5 mg/mL, a 2.5 mg target is 0.5 mL, which is 50 units on a U-100 syringe.
• Change the diluent volume and every unit figure changes. The vial's mg content does not.

Our reconstitution guide works through this in more detail, and the syringe measurement guide covers why unit markings differ between U-100 and U-40 barrels. Both are arithmetic references, not prescribing advice.