Tirzepatide showed fewer heart failure events than dulaglutide

The main SURPASS-CVOT trial compared tirzepatide up to 15 mg weekly with dulaglutide 1.5 mg weekly in people with type 2 diabetes and established blood vessel disease. Treatment lasted an average of about four years ¹. The trial was designed to show that tirzepatide was not worse than dulaglutide on major heart events, and it met that goal ². Major heart events in this trial meant cardiovascular death, heart attack, or stroke ¹.

This new analysis divided participants by whether they had heart failure at the start. Heart failure is a condition where the heart does not pump well enough. Just over 20% of participants had a history of it, and those people also had more coronary artery disease and prior heart attacks ¹. That matters because heart failure raises the chance of future heart and hospital events.

For people with heart failure, tirzepatide was linked to fewer events that combined death from any cause or a hospital visit or urgent visit for heart failure. The hazard ratio was 0.83, with a confidence interval from 0.70 to 0.99 ¹. A hazard ratio below 1 suggests fewer events with the first treatment, and the interval being just below 1 means the estimate is modest rather than certain.

For the composite of heart death or heart failure care, the hazard ratio was 0.85, but the interval included 1.03. For major heart events, the ratios were close to 0.90 or 0.93, and the intervals crossed 1.0. The only broader measure where the interval did not cross 1.0 was MACE-4, which adds coronary revascularization, a procedure to restore blood flow to the heart. There the ratio was 0.81 in the heart failure group ¹.

Patient-reported outcomes also improved on both drugs, and the visual analogue score, a simple measure of self-rated health, was higher on tirzepatide in both groups. These are supportive observations, not proof of cause ¹.

A separate study looked at hearing and balance reports in the FDA adverse event database through early 2026. Researchers found 1,950 unique reports naming a glucagon-like peptide-1 (GLP-1) medicine, a drug class that mimics a gut hormone controlling blood sugar and appetite, the class dulaglutide belongs to, as the main suspect. There were 622 unique reports for dulaglutide, 576 for exenatide, 559 for semaglutide, and 192 for liraglutide ³. The most common problems were hearing loss, vertigo, tinnitus, and deafness ³.

Dulaglutide reports were more likely than class-wide reports to mention hearing loss. The reporting odds ratio was 3.06, with a confidence interval from 2.51 to 3.74 ³. That does not mean dulaglutide causes hearing loss; it only means hearing loss was reported more often with dulaglutide in this database. Other medicines in the same class, such as exenatide and liraglutide, showed different reporting patterns, with more vertigo and tinnitus reports for liraglutide and semaglutide ³. The authors state these findings are hypothesis-generating and do not establish incidence, comparative safety, or causality ³. This does not change the current understanding of dulaglutide's safety, but it adds a question for further study.

Methotrexate is a drug used for chemotherapy and immune conditions, but it can harm the liver. A rat study tested whether dulaglutide could protect against that specific injury. Researchers gave methotrexate to rats for two weeks. Some rats also received dulaglutide under the skin at 0.1 mg per kilogram weekly. The dulaglutide group had lower liver enzyme levels and less evidence of oxidative stress, a type of cell damage from reactive oxygen molecules. Tissue samples also looked less damaged under a microscope ⁴.

This is a short animal study, not human evidence. It suggests dulaglutide has antioxidant properties in this liver injury model. It does not show that dulaglutide prevents drug-induced liver damage in people.

Dulaglutide's heart protection is already known from the REWIND trial, which found a 12% lower risk of major heart events compared with placebo in people with type 2 diabetes ⁵. The SURPASS-CVOT main trial then showed tirzepatide was not worse than dulaglutide on major heart events ². The new analysis adds a narrower question: did the two drugs differ specifically in people with heart failure? The answer is a tentative yes for death or heart failure care, but the evidence is exploratory ¹.

A hearing side effect is not part of the established dulaglutide safety profile. The main approval label does not list hearing loss as a known reaction ⁶, and the pharmacovigilance analysis cannot set incidence ³. The rat liver study fits with other preclinical work suggesting dulaglutide has anti-inflammatory and antioxidant effects in liver tissue ⁷, but it is early.

The heart failure result is exploratory, and the confidence intervals were wide. A dedicated trial would be needed to confirm whether tirzepatide truly reduces heart failure events compared with dulaglutide. The hearing reports come from spontaneous reporting, so we do not know how often hearing problems occur, whether they are reversible, or whether dulaglutide plays a causal role. The rat liver study used one model and a short time frame, and its relevance to human drug-induced liver injury is unproven. None of these findings changes the current evidence that dulaglutide reduces major heart events in type 2 diabetes, but they add open questions.