Cardiovascular-kidney-metabolic (CKM) syndrome describes an interconnected continuum of metabolic, cardiovascular, and kidney disease, with early stages offering an opportunity to delay progression. A retrospective cohort study published in Diabetes Metabolism Research and Reviews found that tirzepatide was associated with a lower risk of progression from CKM stages 1-2 to stages 3-4 compared with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs).

The analysis used data from the TriNetX US Collaborative Network between January 2022 and September 2025. Adults with CKM stage 1 or 2 who newly started tirzepatide or another GLP-1 RA were identified. A new-user design with 1:1 propensity score matching balanced demographic characteristics, comorbidities, medications, and laboratory measures. The primary outcome was progression to CKM stage 3 or 4, defined by incident heart failure, coronary artery disease, ischemic stroke, atrial fibrillation, peripheral artery disease, or very high-risk chronic kidney disease.

After matching, 448,591 patients were included in each group. During one-year follow-up, CKM stage progression occurred in 2.2% of patients receiving tirzepatide and 3.3% receiving GLP-1 RAs. Tirzepatide was associated with lower progression risk (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.86-0.91; P<0.001). Lower risks of major adverse cardiovascular events (MACE) (HR 0.85; 95% CI 0.80-0.89), coronary artery disease, peripheral artery disease, ischemic stroke, heart failure, very high-risk chronic kidney disease, and all-cause mortality were also observed. No significant difference was seen for atrial fibrillation.

Associations remained consistent across prespecified subgroups, including age, sex, baseline CKM stage, obesity status, and statin use. The findings suggest that treatment selection earlier in the CKM continuum may be associated with different short-term disease trajectories.