Tirzepatide Linked to Lower Death or HF Event Rates in T2D, HF

Among patients with type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ASCVD), and a history of heart failure (HF), tirzepatide was associated with a 17% lower risk of all-cause death or hospitalization or urgent visits for HF compared with dulaglutide, according to an exploratory analysis of the SURPASS-CVOT (NCT04255433) trial published in the European Journal of Preventive Cardiology.¹

SURPASS-CVOT previously showed that tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, was noninferior to dulaglutide for the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke (MACE-3) (HR, 0.92; 95.3% CI, 0.83-1.01).² Those results supported the FDA's August 2026 approval of tirzepatide to reduce major adverse CV events in adults with T2D at high CV risk.³ Its effects on HF events and quality of life in patients who also have HF have not been well characterized.

The trial randomly assigned 13,299 patients in 30 countries to once-weekly tirzepatide up to 15 mg or dulaglutide 1.5 mg for an average of about 4 years.¹ In this prespecified subgroup analysis, 20.3% of patients had a self-reported history of HF. These patients had more coronary artery disease and prior MI than those without HF. Patients with New York Heart Association class IV HF or a recent HF hospitalization were excluded.

Fewer Deaths Drove the Heart Failure Composite Result

In patients with HF, the composite of all-cause death or hospitalization or urgent visits for HF, a post hoc end point, occurred in 18.2% of the tirzepatide group vs 21.5% of the dulaglutide group (HR, 0.83; 95% CI, 0.70-0.99). In patients without HF, rates were 8.6% vs 9.7% (HR, 0.88; 95% CI, 0.78-1.00).

All-cause death occurred in 13.5% vs 16.7% of patients with HF (HR, 0.80; 95% CI, 0.65-0.97), whereas hospitalization or urgent visits for HF were nearly identical, at 7.6% vs 7.7% (HR, 0.97; 95% CI, 0.73-1.27). The prespecified composite of CV death or HF events did not reach statistical significance in this group (HR, 0.85; 95% CI, 0.70-1.03). The authors noted that the composite finding was driven predominantly by fatal events.

MACE-4 and Quality of Life Favored Tirzepatide

MACE-3 occurred in 17.2% vs 18.7% of patients with HF (HR, 0.90; 95% CI, 0.76-1.08). With coronary revascularization added (MACE-4), rates were 20.5% vs 24.7% (HR, 0.81; 95% CI, 0.69-0.95).

At 36 months, patients with HF lost 11.2% of body weight with tirzepatide vs 5.1% with dulaglutide, and hemoglobin A_1c fell 1.60 vs 0.90 percentage points. At month 48, tirzepatide-treated patients with HF also had higher Ability to Perform Physical Activities of Daily Living scores (55.3 vs 51.4) and EQ-5D-5L visual analog scale scores (72.1 vs 69.6), with similar gains in patients without HF. Gastrointestinal adverse events were more common with tirzepatide in patients with HF (41.4% vs 34.8%).

The authors called the analysis hypothesis generating and described the differences as nominal, as the analyses were not adjusted for multiple comparisons. SURPASS-CVOT was not designed as an HF trial, HF status was self-reported, and natriuretic peptides and cardiac imaging were not measured, so results could not be separated by HF with reduced vs preserved ejection fraction. More dulaglutide-treated patients also started sodium-glucose cotransporter-2 inhibitors during the trial.

“In summary, treatment with tirzepatide produced favorable effects on CV risk factors, clinical events, and patient-reported outcomes in people with T2D, ASCVD, and with or without a history of HF in this exploratory analysis,” wrote the researchers. “These observations were extended by demonstrating favorable effects of tirzepatide relative to dulaglutide on the composite HF endpoint. These findings further establish the potential benefits of the use of tirzepatide in people with T2D at a high risk of experiencing CV events.”

References

1. Nicholls SJ, Pavo I, Bhatt DL, et al. Outcomes in patients with diabetes, atherosclerotic cardiovascular disease, and heart failure treated with tirzepatide or dulaglutide: SURPASS-CVOT analysis. Eur J Prev Cardiol. Published online October 15, 2026. doi:10.1093/eurjpc/zwag452
2. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409-2420. doi:10.1056/NEJMoa2505928
3. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. News release. Eli Lilly and Company. August 28, 2026. Accessed October 15, 2026. https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-to-reduce-cardiovascular-risk-in-adults-with-type-2-diabetes-302862415.html