Cardiorenal Protective Glucose-Lowering Treatment Patterns in Type 2 Diabetes Mellitus Based on a Real-World Study: A Clinical Phenotype Cluster Analysis

INTRODUCTION: Cardiorenal protective glucose-lowering treatments (CPT), consisting of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), are widely applied in clinical management of patients with type 2 diabetes mellitus (T2DM). This study aimed to identify distinct clinical phenotypes linked to CPT prescribing patterns and construct a multilevel correlation framework for standardized CPT clinical application. METHODS: Data were extracted from the baseline dataset of an observational registry cohort study across 61 medical centers between 2023 and 2024. Based on multiple factors, clinical phenotypes of patients were identified via the Partitioning Around Medoids (PAM) clustering algorithm, CPT utilization was compared across different phenotypes. RESULTS: A total of 9000 patients with T2DM were enrolled [median age 55 (46, 63) years, 60.8% male and 39.2% female, median diabetes duration 5.37 (0.85, 11.44) years]. Three clinically distinct phenotypes were identified: Cluster 1 [older patients with high atherosclerotic cardiovascular disease (ASCVD) risk], Cluster 2 (metabolically stable patients without cardiorenal risk), and Cluster 3 (younger patients with obesity, high metabolic risk and short diabetes duration). The CPT utilization rates of the three clusters were 49.0%, 44.1% and 51.1%, respectively (P < 0.001), with Cluster 3 having the highest rate. Cluster 2 was dominated by SGLT2is monotherapy (73.1%). Cluster 3 showed a marked preference for GLP-1RAs-based regimens (43.6% in total), whereas Cluster 1 had an intermediate proportion of GLP-1RAs-related regimens (31.5%). CONCLUSION: Three clinical phenotypes were identified via cluster analysis. The younger obese group with high metabolic risk had the highest CPT utilization rate and preferred GLP-1RAs, while the older group with high ASCVD risk was predominantly treated with SGLT2is alone. TRIAL REGISTRATION: The trial was registered with https://www.chictr.org.cn/ under registration number ChiCTR230007376 on 20 July 2023.