Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial
In this study (n=2002), the novel dual GIP and GLP-1 receptor agonist tirzepatide was associated with greater HbA1c reductions (−2.43% with 10mg and −2.58% with 15mg vs −1.44% with glargine) and a lower incidence of hypoglycaemia (6–9% vs 19% glargine) at week 52.
Source:
The Lancet
SPS commentary:
A related comment notes that tirzepatide is the first in a new generation of twincretins that combine the actions of GLP-1 with those of the other incretin hormone, gastric inhibitory peptides (GIP). It has previously been compared to placebo, semaglutide and insulin degludec. The SURPASS-4 trial included patients with a baseline HbA1c of 7.5-10.5% despite treatment with metformin, sulfonylureas or SGLT2 inhibitors, or a combination of these. Participants were also at an increased risk of cardiovascular disease, with a history of ischaemic heart, peripheral arterial or cerebrovascular disease, chronic kidney disease, and heart failure.
As well as the observed HbA1c benefits, there was a dose-dependent weight loss of 7.1–11.7 kg with tirzepatide versus a weight gain of 1.9kg with insulin glargine (estimated treatment differences of 9.0–13.5 kg). In addition, there was no overall increased risk of major adverse cardiovascular events (HR 0.74; 95% CI 0.51-1.08, v placebo).
The SURPASS-CVOT trial is comparing tirzepatide against dulaglutide, with a focus on cardiovascular events. Due to complete in 2024, this will hopefully address the question as to whether tirzepatide is capable of improving cardiovascular outcomes to a greater degree than the benchmark GLP-1 analogue dulaglutide.