GLP-1 receptor agonists go head-to-head

A large clinical trial directly compared 2 glucagon-like peptide-1 (GLP-1) receptor agonists in a population of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD), with or without a prior history of heart failure (HF). The late-breaking results favoured one agent over the other.

The SURPASS-CVOT trial (NCT04255433) enrolled 13,299 participants aged ≥40 years with type 2 diabetes and ASCVD. Participants were randomised 1:1 to receive the single-target GLP-1-receptor agonist dulaglutide or the dual GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist tirzepatide. “About 20% of the participants had a history of HF,” said Prof. Stephen Nicholls (Monash University, Australia) [1]. The current analysis evaluated HF outcomes in subgroups of participants with or without prior HF.

In participants with prior HF (HR 0.85; 95% CI 0.70-1.03; P=0.09) and in those without prior HF (HR 0.96; 95% CI 0.83-1.12; P=0.64), no significant difference was observed between tirzepatide and dulaglutide for the composite outcome of cardiovascular death or hospitalisation for HF. However, tirzepatide demonstrated an advantage over dulaglutide regarding all-cause death or hospitalisation for HF, both in participants with prior HF (HR 0.83; 965% CI 0.70-0.99) and in those without prior HF (HR 0.88; 95% CI 0.78-1.00; P=0.05).

“We also observed trends favouring tirzepatide for several second measures, including patient-reported outcomes (transformed total score of Ability to Perform Physical Activities of Daily Living [APPADL]), post-baseline sodium-glucose co-transporter 2 (SGLT2) inhibitor uptake, change in baseline estimated glomerular filtration rate (eGFR), body weight, blood pressure, and haemoglobin A1c,” emphasised Dr Nicholls. The safety profiles of both agents were broadly comparable, though gastrointestinal events were somewhat more frequent with tirzepatide.

Overall, SURPASS-CVOT suggests that tirzepatide may confer more favourable effects on HF-related outcomes than dulaglutide in patients with type 2 diabetes, regardless of prior HF.

1. Nicholls SJ, et al. Once-weekly tirzepatide versus dulaglutide for heart failure outcomes in patients with type 2 diabetes, ASCVD and history of heart failure: an analysis of SURPASS-CVOT. AHA scientific sessions 2025, 7-10 November, New Orleans, LA, USA.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 13 November 20255 December 2025