A heart-failure signal in a diabetes trial needs its own test

On 15 October 2026 the European Journal of Preventive Cardiology published a new analysis of SURPASS-CVOT, a large double-blind trial in adults with type 2 diabetes and established atherosclerotic cardiovascular disease, meaning narrowed arteries in the heart, brain or legs. Participants had been randomly assigned to a weekly injection of either tirzepatide, which acts on two gut-hormone receptors (GLP-1 and GIP), or dulaglutide, an older GLP-1 medicine already shown to reduce cardiovascular events. Both are FDA-approved treatments for type 2 diabetes. The analysis compared people with and without a history of heart failure recorded at enrolment.

One in five already had heart failure, and they had more events on either drug

A history of heart failure was recorded in 20.3% of participants. This group more often had coronary artery disease and a previous heart attack, and every category of event was more frequent in it. Over an average of four years, people with heart failure had fewer combined events of death from any cause or a hospital stay or urgent visit for heart failure on tirzepatide than on dulaglutide: hazard ratio 0.83 (95% CI 0.70–0.99). In people without heart failure the same comparison gave 0.88 (0.78–1.00).

A broader cardiovascular measure that also counts procedures to reopen the coronary arteries pointed the same way: hazard ratio 0.81 (0.69–0.95) with heart failure and 0.91 (0.83–1.00) without. Patient-reported scores for daily activities and general health were higher on tirzepatide in both groups.

On heart attack, stroke and cardiovascular death, the two drugs did not separate

For the classic trio of cardiovascular death, heart attack or stroke, the hazard ratios were 0.90 (0.76–1.08) in people with heart failure and 0.93 (0.83–1.04) in those without. Both intervals include no difference at all. The same was true for cardiovascular death or heart-failure events: 0.85 (0.70–1.03) and 0.96 (0.83–1.12).

The main trial was built to show "not worse", and that is what it showed

The parent trial, published in the New England Journal of Medicine in December 2025, randomised 13,299 people; 13,165 remained in the analysis after exclusions. Their mean age was 64, 29% were women, and they had lived with diabetes for about 15 years on average. The main question was whether tirzepatide was no worse than dulaglutide for cardiovascular death, heart attack or stroke. It passed that test: such events occurred in 12.2% of people on tirzepatide and 13.1% on dulaglutide (hazard ratio 0.92; 95.3% CI 0.83–1.01), but superiority was not shown. Gastrointestinal side effects were more frequent with tirzepatide.

The comparison was demanding by design. In the earlier REWIND trial, 9,901 people aged 50 or older with type 2 diabetes and either cardiovascular disease or risk factors received dulaglutide or placebo, and the same combined outcome was less frequent with dulaglutide (hazard ratio 0.88; 0.79–0.99). SURPASS-CVOT therefore measured a newer medicine against one that already works, not against a dummy injection.

A subgroup finding is a lead for the next trial, not a settled answer

The authors describe the heart-failure analysis as exploratory. Slicing a trial into subgroups raises the chance of finding a difference by luck, and the paper reports no evidence that treatment effects on the composite heart-failure endpoints differed by prior heart-failure history. Several of the intervals end at or just below 1.00. The trial was funded by Eli Lilly, the maker of tirzepatide; six authors are company employees and many others report payments from drug manufacturers. Everyone enrolled had both diabetes and established arterial disease, so the result says nothing about people without them. The trial also excluded people with NYHA class IV heart failure or a heart-failure hospital stay in the two months before enrolment. Heart failure here means a recorded history of the diagnosis; the summary does not break it down by type or severity.

If you live with type 2 diabetes together with heart disease or heart failure, which of these medicines suits your situation is a question to discuss with your doctor.

This material is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.

Sources

• Nicholls SJ, 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. 2026. PMID 42875024

• Nicholls SJ, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025. PMID 41406444

• Gerstein HC, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019. PMID 31189511

• SURPASS-CVOT — The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes. ClinicalTrials.gov. NCT04255433