Lilly withdraws its US heart failure application for tirzepatide
Eli Lilly pulled its US application to add a heart failure indication (HFpEF) to tirzepatide after the FDA asked for another confirmatory trial — though the company says affected patients are already covered by the obesity indication.
Eli Lilly has withdrawn its US application to have tirzepatide approved for heart failure with preserved ejection fraction (HFpEF) after the FDA said an additional confirmatory trial would be needed, the company's chief scientific officer told investors [1].
The disclosure came during a Lilly investor briefing, where Dan Skovronsky said: "Following discussions with the FDA, we've withdrawn our U.S. application for the heart failure with preserved ejection fraction indication for tirzepatide. We believe the positive phase three data from the SUMMIT trial do support an indication. However, FDA indicated an additional confirmatory clinical trial is required. Regulatory reviews are ongoing in other countries" [1].
HFpEF is a form of heart failure in which the heart muscle stiffens and does not fill properly, even though the pumping fraction looks normal. Lilly's SUMMIT trial tested tirzepatide in this group and was published in the New England Journal of Medicine [1]. Skovronsky described it as "a study with a really strong and profound benefit for patients," adding that "from the FDA perspective, they want multiple trials to support this indication" [1]. The specific effect sizes from SUMMIT are not detailed in the available sources.
What the withdrawal does and does not change
Skovronsky made a point that matters for anyone already taking the drug: the people studied in SUMMIT are, in the US, already eligible under the existing obesity indication. "All the patients in this trial and for this indication are already covered under the obesity indication," he said. "So it's not a new population to treat. It's rather a new benefit for people that might already be understood to doctors today" [1].
He also warned about a broader chilling effect on research: "It could have a curtailing effect on investments in HFpEF — which is a pretty serious unmet medical need. So I'm sorry to see that. But it's kind of hard to think of the incentive for doing large outcome trials in this population that's already covered under an existing indication if the benefits are well understood" [1]. He said it is "possible we could get additional data from other trials to support a resubmission" [1].
The situation is not unprecedented. Novo Nordisk withdrew its FDA submission for semaglutide (Wegovy) in HFpEF and then resubmitted it, supported in part by a published pooled analysis of heart failure outcomes from four earlier studies [1].
Why it matters for patients
A withdrawn application is a regulatory event, not a reversal of the trial results. Tirzepatide (marketed as Zepbound for obesity and Mounjaro for type 2 diabetes) remains available under its existing approved uses [1]. What changes is the label: without an HFpEF indication, the FDA-approved prescribing information will not list heart failure as a treatment use, and Lilly cannot market it for that purpose.
That can matter for insurance. Coverage decisions often lean on approved indications, so patients with obesity and HFpEF may find their access hinges on the obesity indication rather than a cardiac one — a distinction that can affect which plans pay and under what rules. The sources do not report how insurers have responded, so that remains unclear.
There is also a research question. Skovronsky's comments suggest drugmakers may be less willing to fund large, expensive outcome trials in HFpEF if the eligible patients are already covered by a weight-related indication [1]. That could slow the accumulation of evidence doctors use to weigh treatment options.
What happens next
Lilly said reviews in other countries were continuing at the time of the May 2025 briefing [1]. In Europe, the outcome was negative: on January 30, 2026, Endpoints News reported that the EMA's human medicines committee (CHMP) had refused to recommend Mounjaro as a treatment for a type of heart failure, while backing Novo Nordisk's Kayshild for liver disease [2].
Whether Lilly will run or pool additional trials to support a US resubmission has not been announced.
Sources
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