A new analysis sheds light on the timing of protection offered by SGLT2 inhibitors. Researchers conducted a cross-trial analysis using individual participant data from four large-scale randomized clinical trials: CANVAS (type 2 diabetes with high atherosclerotic risk, NCT01032629), CREDENCE (diabetic kidney disease, NCT02065791), DAPA-HF (heart failure with reduced ejection fraction, NCT03036124) and DELIVER (heart failure with mildly reduced or preserved ejection fraction, NCT03619213).[1]

The analysis[2] revealed variations in the relative timing of benefits across different patient groups. HF hospitalisations emerged as the earliest prevented event across all populations. Additionally, major adverse cardiovascular events (MACE) showed relatively early benefits in the CANVAS and CREDENCE trials. The researchers estimated that SGLT2 inhibitor therapy could potentially prevent 275 to 335 hospitalizations for heart failure per 10,000 patients at 12 months based on data from the DAPA-HF and DELIVER trials.

Progression of CKD displayed a different pattern. As expected, the highest projected number of prevented events was observed in the CREDENCE trial, which focused on patients with diabetic kidney disease. The number of prevented CKD events, MACE events, and hospitalisations for HF increased in parallel, showing approximately equivalent protection until around 24 months. However, by 36 months, CKD prevention surpassed both MACE and HF benefits (388 vs 271 and 289 prevented events per 10,000 patients treated, respectively).

These findings suggest that while the timing and number of prevented events with SGLT2 inhibitors vary across the cardio-renal spectrum, the opportunity to modify risk factors emerges early, particularly for HF and MACE outcomes. 

Talking with Radcliffe Cardiology, investigator Dr Mutiah Vaduganathan commented, “Importantly SGLT2 inhibitors have early effects on heart failure as well as MACE endpoints in these treated populations .”[3]
 

Sources

[1] HFA 2024: Vaduganathan M: Timing of Cardio-Kidney Protection with SGLT2 Inhibitors: Insights from Four Large-scale Placebo-Controlled Outcome Trials. https://esc365.escardio.org/presentation/283460

[2] Neuen LB,  Claggett BL,  Perkovic V, et al. Circulation 2024. Timing of Cardio-Kidney Protection With SGLT2 Inhibitors: Insights From Four Large-Scale Placebo-Controlled Outcome Trials

[3] Radcliffe Cardiology. ESC-HFA 2024: Late-Breaking Science Video Collection. Vaduganathan M: Timing of Cardio-Kidney Protection with SGLT2i