Real world data showed that the dual GLP gip agonist, Tirzepatide is associated with lower mortality, cardiovascular events and adverse kidney events compared with GLP-1 analogue

Tirzepatide is a novel, dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) analogue. Studies have shown superiority of Tirzepatide compared with Semaglutide, a once weekly GLP-1 agonist in reducing HbA1c and weight, but whether these metabolic improvements lead to improvements in cardiovascular and kidney outcomes remains unclear. Semaglutide meanwhile has been shown to reduce cardiovascular events and reduce risk of heart failure progression in patients with or without type 2 diabetes.^{1, 2} There is currently no studies which have directly compared tirzepatide with GLP-1 RAs.

In view of this, the publication in the journal JAMA Network Open comparing the cardio-renal benefits of Tirzepatide versus Semaglutide in people with type 2 diabetes is welcoming.³

This was retrospective cohort study using US Collaborative Network of TriNetX data and collected clinical information of individuals with type 2 diabetes aged 18 years. Patients with stage 5 chronic kidney disease or kidney failure at baseline; myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation were excluded. The primary outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACEs), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events.

14 834 patients treated with tirzepatide and 125 474 treated with GLP-1 RA were analysed. Mean age was 58.1 years. After a median follow-up of 10.5 months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with a 42% lower risk of all-cause mortality, 20% lower risk of Major Adverse Cardiovascular events (MACE) and 24% reduced risk of combined all-cause mortality and MACE. Kidney events was also reduced by 48%, acute kidney injury by 22% and major adverse kidney events by 46% with Tirzepatide compared with Semaglutide. Perhaps unexpectedly, treatment with tirzepatide was also associated with greater decreases in glycated haemoglobin (treatment difference, −0.34 percentage points) and body weight (treatment difference, −2.9 kg compared with semaglutide. An interaction test for subgroup analysis revealed consistent results when stratified by estimated glomerular filtration rate, glycated haemoglobin level, body mass index, concurrent therapies and comorbidities.

While this is a retrospective study with its usual caveat and limitations – namely allocation bias and residual confounders, evidence from this study provide novel and preliminary evidence of the effectiveness of Tirzepatide when used in routine clinical practice compared with Semaglutide. I look forward to evidence of cardio-renal benefits of Tirzepatide in a randomized clinical trial setting, especially when compared with high dose Semaglutide at 2.4 mg once weekly.