Traditional Cardiometabolic Risk Factors, Not GLP-1 RAs or SGLT2is, Predict ASCVD in T2D/MASLD

Patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) face a significantly elevated risk of atherosclerotic cardiovascular disease (ASCVD). While both conditions are known to contribute to cardiovascular morbidity, the precise hierarchy of risk factors — whether traditional cardiometabolic factors, markers of hepatic fibrosis, or even the use of modern antidiabetic therapies — in predicting ASCVD in this specific population remains underexplored. Understanding these relative contributions is crucial for optimizing risk stratification and therapeutic strategies, as current standard-of-care often focuses on individual components rather than their integrated impact.

Researchers conducted a cross-sectional study involving 46 patients diagnosed with both T2D and MASLD. Atherosclerotic cardiovascular disease (ASCVD) was defined by the presence of carotid atheromatosis, stroke, peripheral arterial disease, or ischemic heart disease, confirmed via imaging. The study analyzed various clinical, metabolic, and treatment-related variables, including age, Hemoglobin A1c (HbA1c), lipid profiles, and hepatic fibrosis indices such as Fibrosis-4 index (FIB-4). They also assessed the use of antidiabetic therapies, specifically sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and insulin. Multivariable regression models and receiver operating characteristic (ROC) curve analyses were employed to evaluate associations and predictive performance.

The study revealed that traditional cardiometabolic risk factors (CMRFs) were more strongly associated with ASCVD than either hepatic fibrosis markers or antidiabetic therapies. Age showed an association with ASCVD in exploratory models, though this effect was attenuated after full adjustment. HbA1c demonstrated the highest discriminative performance for ASCVD, achieving an AUC of 0.77. This indicates that chronic glycemic exposure is a primary determinant of vascular disease within this specific cohort. In contrast, the FIB-4 index, a marker of hepatic fibrosis, was not significantly associated with ASCVD and did not enhance the predictive power of the models. Antidiabetic therapies, including SGLT2is and GLP-1 RAs, were not independently associated with ASCVD in this analysis. Although insulin therapy was more frequently observed among patients with ASCVD, this association did not remain independent after adjusting for other variables.

HbA1c exhibited the strongest discriminative performance for ASCVD, with an AUC of 0.77, highlighting its critical role over other factors.