Peptides for weight loss: what the trials actually measured

Four peptides have large randomized weight-loss trials behind them, and their results are public down to the decimal point. Most of the other compounds marketed for fat loss have nothing comparable, and the gap between those two groups is the whole story.

Published September 14, 2026

This page reports what published studies found. It is not medical advice, no provider-patient relationship is created by reading it, and nothing here is a recommendation to use any compound. Talk with a licensed clinician about your own situation. Read the full disclaimer.

The four with real trials

The peptides with serious weight-loss evidence all work on incretin receptors: the gut hormone pathways that tell the body a meal has arrived. Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on GLP-1 and GIP. Retatrutide adds the glucagon receptor and was still in trials at the time of writing. Cagrilintide targets a different pathway, amylin, and has been studied both alone and in combination.

Semaglutide: STEP 1

STEP 1 enrolled 1,961 adults with a body-mass index of 30 or more, or 27 or more with at least one weight-related condition, and without diabetes. Participants were randomized two to one to 68 weeks of once-weekly subcutaneous semaglutide at 2.4 mg or placebo, both with lifestyle intervention. Mean body weight changed by -14.9 percent with semaglutide and -2.4 percent with placebo, a treatment difference of -12.4 percentage points. In absolute terms that was -15.3 kg against -2.6 kg. Weight reductions of at least 5 percent occurred in 86.4 percent of the semaglutide group and 31.5 percent of the placebo group; reductions of at least 15 percent occurred in 50.5 percent and 4.9 percent.

Tirzepatide: SURMOUNT-1

SURMOUNT-1 randomized 2,539 adults without diabetes to once-weekly tirzepatide at 5, 10 or 15 mg or placebo for 72 weeks, including a 20-week dose-escalation period. Mean percentage weight change at week 72 was -15.0 percent at 5 mg, -19.5 percent at 10 mg and -20.9 percent at 15 mg, against -3.1 percent with placebo. In the 15 mg group, 57 percent of participants lost at least 20 percent of body weight. Mean baseline weight was 104.8 kg.

Retatrutide: phase 2

Retatrutide's phase 2 trial enrolled 338 adults and ran 48 weeks across several dose groups. At 48 weeks the least-squares mean change in body weight was -8.7 percent in the 1 mg group, -17.1 percent in the combined 4 mg groups, -22.8 percent in the combined 8 mg groups and -24.2 percent in the 12 mg group, against -2.1 percent for placebo. A phase 2 trial is a dose-finding study, not a registration trial, and those figures come from 338 people rather than several thousand.

What the withdrawal trials showed

The most decision-relevant evidence is not the headline loss but what happened when treatment stopped, and two trials were designed specifically to test that.

STEP 4 ran a 20-week run-in during which 902 participants took semaglutide and lost a mean of 10.6 percent. The 803 who reached the maintenance dose were then randomized two to one to continue or to switch to placebo for 48 more weeks. Continuing produced further loss; switching to placebo produced regain.

SURMOUNT-4 did the same with tirzepatide: 783 adults took it openly for 36 weeks and lost a mean of 20.9 percent, then 670 were randomized to continue or switch to placebo for 52 weeks. From week 36 to week 88, mean weight change was -5.5 percent with continued tirzepatide and +14.0 percent with placebo. At week 88, 89.5 percent of those still on tirzepatide had kept at least 80 percent of their lead-in weight loss, against 16.6 percent on placebo.

These are the numbers that make the cost question a recurring one rather than a one-time one, which is why we wrote a separate guide on what treatment costs over time.

Semaglutide versus tirzepatide

Cross-trial comparisons are unreliable, but one randomized head-to-head exists, in a different population. SURPASS-2 assigned 1,879 people with type 2 diabetes to tirzepatide at 5, 10 or 15 mg or semaglutide at 1 mg for 40 weeks. Tirzepatide was superior on the primary glycated hemoglobin endpoint at all doses, and weight reductions were greater with tirzepatide, by an estimated -1.9, -3.6 and -5.5 kg respectively. Note the semaglutide dose there was 1 mg, the diabetes dose, not the 2.4 mg used for weight management, and everyone in the trial had diabetes.

Side effects the trials recorded

• Gastrointestinal. Nausea and diarrhea were the most common adverse events with semaglutide in STEP 1, typically transient and mild to moderate.
• Discontinuation. In STEP 1, 4.5 percent of the semaglutide group stopped treatment because of gastrointestinal events, against 0.8 percent on placebo.
• Dose escalation. Both phase 3 obesity trials built in long escalation periods, 16 weeks in STEP 1 and 20 in SURMOUNT-1, which is part of why those tolerability numbers look the way they do.

The compounds without trials

A large amount of marketing attaches the word "peptide" to fat loss without any of the evidence above. AOD-9604, MOTS-c and 5-amino-1MQ are common examples, generally sold as research chemicals rather than prescribed. Growth hormone secretagogues such as sermorelin are marketed for body composition on the strength of mechanism rather than outcome trials. Tesamorelin is approved, but for reduction of excess abdominal fat in HIV-associated lipodystrophy, a specific condition rather than general weight management.

This is not a claim that those compounds do nothing. It is a claim about what is known. Each compound page lists its evidence with species and sample sizes attached, so the difference between "no trial has been run" and "a trial found no effect" stays visible.

Branded, compounded, and grey-market versions

The same molecule reaches people three ways, and they are not equivalent. The branded product is the one studied in the trials above. A compounded preparation is made by a pharmacy for an individual patient under a prescription; it may be the only accessible option during a shortage, but it was not the product tested. A vial bought from a research-chemical vendor is sold as not for human use, with no pharmacy oversight of strength or sterility. Our legal guide covers how regulators treat each route, and the vendor index documents what that market looks like in 2026.

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