Comparative Effectiveness of Sodium-Glucose Co-transporter 2 Inhibitors and Thiazolidinediones in Reducing Adverse Cardiovascular Events in Type 2 Diabetes

Background Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). While both sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and thiazolidinediones (TZDs) have demonstrated cardiovascular effects, comparative data in real-world South Asian populations remain limited. Objective This study aimed to compare the effectiveness of SGLT-2is and TZDs in reducing adverse cardiovascular events (ACVEs) in patients with T2DM. Methodology A prospective, comparative cohort study was conducted at HITEC Institute of Medical Sciences, Taxila, from January to December 2024. A total of 240 T2DM patients with high cardiovascular risk were recruited and divided equally into two groups: one receiving SGLT-2is (dapagliflozin or empagliflozin) and the other receiving TZDs (pioglitazone). Baseline clinical and biochemical parameters were recorded and followed for 12 months. Outcomes included changes in blood pressure, body mass index (BMI), glycemic and lipid profiles, renal function, and incidence of major adverse cardiovascular events (MACE). Results At baseline, both groups were comparable in age (mean 56.4±9.8 years), sex distribution (58% male), and hypertension duration (8.6±5.1 years). After 12 months, the SGLT-2is group showed greater reductions in systolic blood pressure (130.5±9.1 mmHg vs. 134.7±10.2 mmHg; p<0.05), BMI (28.7±3.4 vs. 29.9±3.6 kg/m²), and HbA1c (7.1±0.7% vs. 7.4±0.8%). Lipid profiles and fasting glucose also improved more in the SGLT-2is group. The incidence of MACE was significantly lower in the SGLT-2is group (8.3%) compared to the TZD group (21.7%), with fewer cardiovascular deaths, myocardial infarctions, strokes, and heart failure hospitalizations. Conclusion SGLT-2is demonstrated superior cardiometabolic outcomes and a lower risk of ACVEs compared to TZDs, supporting their preferential use in patients with T2DM at elevated cardiovascular risk.