Abstract: TH-OR53
Modeling Cardiorenal Protection with SGLT2 Inhibition in Type 1 Diabetes: An Analysis of EASE-2 and -3
Session Information
- Diabetic Kidney Disease - Clinical: Novel Insights into Precision Medicine
October 24, 2024 | Location: Room 33, Convention Center
Abstract Time: 05:40 PM - 05:50 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Kugathasan, Luxcia, Toronto General Research Institute, Toronto, Ontario, Canada
- Dutta, Pritha, University of Waterloo, Waterloo, Ontario, Canada
- Nardone, Massimo, Toronto General Research Institute, Toronto, Ontario, Canada
- Sridhar, Vikas, Toronto General Research Institute, Toronto, Ontario, Canada
- Campbell, David, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Layton, Anita T., University of Waterloo, Waterloo, Ontario, Canada
- Perkins, Bruce A., Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
- Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
- Lam, Tony K.T., Toronto General Research Institute, Toronto, Ontario, Canada
- Levin, Adeera, The University of British Columbia, Vancouver, British Columbia, Canada
- Lovblom, Leif Erik, Toronto General Research Institute, Toronto, Ontario, Canada
- Mucsi, Istvan, Toronto General Research Institute, Toronto, Ontario, Canada
- Rabasa-Lhoret, Remi, Universite de Montreal, Montreal, Quebec, Canada
- Rac, Valeria E., Toronto General Research Institute, Toronto, Ontario, Canada
- Senior, Peter A., University of Alberta, Edmonton, Alberta, Canada
- Sigal, Ronald J., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Stanimirovic, Aleksandra, Toronto General Research Institute, Toronto, Ontario, Canada
- Doria, Alessandro, Harvard Medical School, Boston, Massachusetts, United States
- Cherney, David, Toronto General Research Institute, Toronto, Ontario, Canada
Background
Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduce cardiorenal risk in people with type 2 diabetes. It is unknown if these protective effects extend to individuals with type 1 diabetes (T1D). To better understand the potential benefits of SGLT2 inhibition in T1D, we applied the Steno T1 risk engine (SRE) and Scottish Diabetes Research Network (SDRN) risk prediction models to estimate risk of cardiovascular disease (CVD) and end-stage kidney disease (ESKD) in two large T1D cohorts.
Methods
Medical history, demographic and biomarker data were extracted from 730 and 960 participants with T1D from the EASE-2 and 3 trials, respectively. The SRE and SDRN risk prediction models were employed at baseline, week 26 (EASE-3) or 52 (EASE-2), and 3 weeks post drug washout to estimate the 10-year CVD and 5-year ESKD risk. Risk reduction was calculated as the percent change in estimated CVD and ESKD risk from baseline between empagliflozin (pooled 10 and 25mg) vs. placebo groups, and compared using a two-way repeated measures ANOVA.
Results
Empagliflozin significantly reduced the estimated 10-year CVD risk following 26 weeks (SRE: -9.6% [-12.1, -7.1] & SDRN: -22.4% [-28.1, -16.6]; p<0.01) and 52 weeks (SRE: -9.2% [-11.6, -6.9] & SDRN: -16.7% [-20.7, -12.7]; p<0.01) of treatment compared with placebo. No significant reduction in 5-year ESKD risk was observed while on treatment. The ESKD risk was significantly lower after a 3-week drug washout (SRE: -8.4% [-15.1, -1.7] (EASE-3) & -9.7% [-13.5, -6.0] (EASE-2); p<0.01), in keeping with the expected rise in eGFR.
Conclusion
Empagliflozin improves predicted CVD and ESKD risk in T1D participants, thus demonstrating the need for dedicated outcome trials in patients with T1D and established kidney or cardiovascular disease. ESKD risk estimation using GFR-based models may be best implemented after drug washout as to avoid the reversible hemodynamic eGFR “dip” with SGLT2 inhibition.