Peptide basics

What a boxed warning is, and which of these products carry one

This page explains a labelling requirement and reports which labels currently carry it. It does not rank products by danger, does not say any product is safe or unsafe, and gives no advice about use — that requires someone who can examine you.

The definition, not the folklore

The boxed warning is defined in the labelling regulation at 21 CFR 201.57(c)(1). In the regulation's own terms, certain contraindications or serious warnings — particularly those that may lead to death or serious injury — may be required by FDA to be presented in a box, which must briefly explain the risk and point to the fuller text in the contraindications or warnings sections.¹

The next sentence of that paragraph is the one that explains the GLP-1 boxes specifically: a boxed warning ordinarily must be based on clinical data, but serious animal toxicity may also be the basis of a boxed warning in the absence of clinical data. That is exactly the situation these products are in, and the regulation anticipated it.¹

FDA's guidance on the warnings, contraindications and boxed warning sections sets out how the text is written and what belongs in each section. Both documents describe a labelling requirement and a decision procedure. Neither defines a scale, a grade or a comparison between products.¹²

How this list was checked

FDA publishes structured product labelling through the openFDA labelling endpoint, where a label either has a boxed_warning field or does not. Every entry below was read that way and then linked to the published label itself, so the presence or absence of a box is a property of the document rather than our reading of it.³

Which of these carry one

Wegovy carries a boxed warning headed risk of thyroid C-cell tumours, stating that in mice and rats semaglutide caused a treatment-duration-dependent increase in those tumours at clinically relevant exposures, and that it is unknown whether the product causes them in humans because the human relevance of the rodent finding has not been determined.⁴

The shared Ozempic and Rybelsus label carries the same warning for semaglutide. Zepbound and Mounjaro carry the equivalent for tirzepatide, citing rat studies. Saxenda and Victoza carry it for liraglutide, citing both rats and mice. Trulicity carries it for dulaglutide.^5678910

• Every one of these boxes concerns the same finding class: thyroid C-cell tumours in rodents.
• Every one of them states that human relevance has not been determined.
• Each is paired with the same contraindication: a personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2.
• None of them states a frequency, because a boxed warning is not where frequencies go.⁴⁶⁸¹⁰

Which do not

The currently published Byetta label — twice-daily exenatide, a GLP-1 receptor agonist — has no boxed warning field at all. Same receptor class, different product, different application, different labelling outcome.¹¹

Egrifta, the tesamorelin product, likewise carries none in its currently published labelling. It is worth stating for a site about peptides: an approved peptide product with no boxed warning exists, and that fact is about its own review record rather than about peptides.¹²

Exenatide is the class counterexample: a GLP-1 receptor agonist whose currently published US label carries no boxed warning.

Tesamorelin is one of the few peptides on this site with an approved US product to read a label from at all. Most compounds in the directory have no label, which is a different situation from having a label with nothing in the box.

What a box cannot tell you

It cannot tell you how likely the hazard is. The regulation asks for a brief explanation of the risk and a pointer to the fuller text; frequencies live in the adverse reactions section, where they are printed against a placebo column with participant numbers.¹

It cannot be compared across products as a ranking. Boxes are added, revised and occasionally removed as evidence and review decisions change, and two boxes triggered by different criteria are not two points on one scale.¹²

And its absence carries almost no information for anything unapproved. A compound with no FDA-approved product has no label, therefore no box, therefore nothing to read — which is not the same as a label that was reviewed and did not need one.³¹²

Common questions