New U.S. FDA Letter Contradicts Decades-Old Precedent on Prescription Drug Promotion

As noted in a prior Update, U.S. Food and Drug Administration (FDA) officials began a “crackdown” on direct-to-consumer (DTC) advertising of prescription drugs in September 2025, including by issuing a number of warning and untitled letters to the manufacturers of approved medicines. FDA has articulated positions in many of these letters that raise significant constitutional, legal, and regulatory concerns. A recent untitled letter is a particularly striking example because it directly conflicts with the position FDA took in a warning letter issued more than 20 years ago, which recognized that factual statements about a medical product’s approved indications are truthful, nonmisleading, and not objectionable.

The crackdown began on September 9, 2025, with multiple announcements by the White House, the Department of Health and Human Services (HHS), and FDA, along with the simultaneous issuance of over 60 warning and untitled letters targeting DTC advertisements for FDA-approved prescription drugs. Since then, the FDA Office of Prescription Drug Promotion (OPDP) has continued to issue letters alleging promotional violations at a pace industry has not experienced in many years. Based on letters publicly disclosed as of March 9, OPDP has already issued at least nine letters in 2026, putting it on track to exceed 50 letters this year — compared to only five in all of 2024.

The latest letter targets a DTC video for a well-known injectable incretin medicine approved to treat Type 2 diabetes in adults, which included factual statements that the drug has “the most FDA-approved uses” in its class. According to the letter, statements along these lines “create a misleading impression” that the product is superior.

It’s not entirely clear what is motivating FDA here. To the extent the agency is truly concerned about a comparison of approved indications, its position here stands in stark contrast to the position taken in a 2005 warning letter concerning Zyrtec (cetirizine) tablets. There, FDA said that a DTC ad misleadingly implied superiority through statements that Zyrtec “works” and suggestions that competing allergy medicines do not. But the 2005 letter did not object to factual comparisons of indications, including the statement “No other antihistamine is approved to treat more allergies than Zyrtec.” FDA made clear that this comparison was permissible because “FDA does not object to the dissemination of truthful, non-misleading statements about approved indications, and we acknowledge that Zyrtec is approved for a broader range of indications than many other antihistamines.”

Alternatively, the latest letter can be seen as an objection to creativity in drug advertising. Long ago in a context far away, FDA sought to limit ads for tobacco products to black text on a white background. The courts struck that down as an unconstitutional restraint on commercial speech, but FDA’s letters since last fall have been trending in a similar direction for drug ads. For instance, a letter in February construed such “imagery” as “an elderly man … walking his dog” as a “quality of life” claim. And a letter in January asserted that images of patients walking, driving, purchasing food, swinging a golf club, and sharing a meal were all somehow “misleading.” In a similar vein, the latest letter objects to the inclusion of an attempt “to lighten the situation” through a “comedic device” involving a “bird-calling response” on the grounds that it implied that other incretins “are not worthy of substantive discussion” or “lack meaningful benefits.” It also objects to “the visual representation of the characters” in the videos, including the fact that a character representing the advertised drug was in “a bright, orange shirt” while another representing other drugs in the class was in “a dull, gray shirt,” which supposedly “implies superiority.”

It is unlikely that FDA has any evidentiary support for any of these objections. It seems far more likely that FDA has adopted the “‘I know it when I see it’” approach to regulating imagery in advertising and that FDA will now see “it” when any kind of creativity is involved in a DTC ad for a prescription drug.

That said, we are aware of prior research by OPDP that could be influencing the agency here. It involved experiments in which participants viewed print and video ads for a fictitious drug; one finding was that comparisons of approved indications, versus comparisons of dosing method, resulted in increased perception of better efficacy for the advertised drug. The published results of that research explicitly noted, however, that the findings merely “support further investigation of the effects of comparative claims in DTC advertising” and that they showed that “comparative claims in DTC ads could mislead consumers about a drug’s efficacy and risk” and “may influence the perceived efficacy of the drug, even when the ads do not compare efficacy” (emphasis added). The strength of the findings as a basis for enforcement is also questionable given that there was a significant increase in perception of better efficacy only for the video ads (which was not replicated for the print ads) and that there was also a directional increase in perception of comparative risk for the print ads.

FDA’s attack on creativity in prescription drug ads also reflects a troubling double standard: Ads for approved incretins seem to receive more frequent and more stringent scrutiny than ads for unapproved knockoffs. Yes, the September 2025 crackdown included letters objecting to claims that falsely imply equivalence between approved and unapproved drugs (a point FDA repeated in February and alluded to again more recently). FDA also has objected to marketing that obscures the true source of an unapproved drug. But anyone on social media knows that the channels remain stuffed with actually misleading advertising for knockoff incretins, including promotion with explicit claims that the knockoffs are superior.

In any event, FDA’s crackdown seems destined to collide with the well-established principle that truthful and nonmisleading speech — including commercial speech — is entitled to substantial First Amendment protection. That principle requires meaningful evidentiary and analytical support for enforcement-related actions that, at bottom, target the alleged implications of factual statements about an approved prescription product. Such support appears lacking here, where the letter itself relies on the assertion that a comedic tone and contrasting color scheme are sufficient to imply superiority.

More broadly, this development raises significant questions regarding the predictability and stability of FDA precedent, the evidentiary basis required for promotion-related enforcement actions, and the potential for constitutional and administrative law challenges where truthful, nonmisleading speech is targeted. In this evolving environment, proactive risk assessment, thoughtful substantiation practices, and close monitoring of further OPDP activity will be critical to mitigating enforcement risk while preserving robust, accurate, and socially valuable communication about approved prescription drugs.

Going forward, prescription drug manufacturers — particularly those engaged in DTC promotion — should carefully assess both existing campaigns and future creative strategies in light of this and other potential shifts in FDA’s promotion policy. Companies may wish to implement enhanced legal and regulatory review of comparative messaging, even where it is limited to factually accurate statements regarding approved indications, and to document the substantiation and rationale supporting such claims. Sponsors should also evaluate whether FDA could characterize tone, imagery, and other creative elements as implying unsubstantiated superiority even in the absence of express comparative claims.