Abstract: FR-PO312
Modeling Cardiorenal Protection with SGLT2 Inhibition in Type 1 Diabetes: An Analysis of DEPICT-1 and -2
Session Information
- Diabetic Kidney Disease: Clinical Modeling, Diagnosis, Education, and More
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Nardone, Massimo, Toronto General Research Institute, Toronto, Ontario, Canada
- Kugathasan, Luxcia, Toronto General Research Institute, Toronto, Ontario, Canada
- Sridhar, Vikas, Toronto General Research Institute, Toronto, Ontario, Canada
- Dutta, Pritha, University of Waterloo, Waterloo, 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., Sinai Health, Toronto, Ontario, Canada
- Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
- Lam, Tony K.T., University of Toronto, 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., University of Toronto, 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, University of Toronto, Toronto, Ontario, Canada
- Doria, Alessandro, Harvard Medical School, Boston, Massachusetts, United States
- Cherney, David, Toronto General Research Institute, Toronto, Ontario, Canada
Background
Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycemic control and lower insulin requirements in type 1 (T1D) and type 2 diabetes (T2D). While SGLT2 inhibitors lower cardiovascular disease (CVD) and end-stage kidney disease (ESKD) risk in T2D, dedicated cardiorenal outcome trials have not been performed in T1D. Using validated risk prediction models, the current analysis evaluated the effect of SGLT2 inhibition on estimated CVD and ESKD risk in a T1D cohort.
Methods
Demographics, medical history, biomarkers, and blood pressure were extracted from 1,473 participants with T1D enrolled in the DEPICT-1 and -2 trials. Data at baseline, week -24, -52, and -56 (4 weeks off-treatment) were used to estimate 10-year CVD and 5-year ESKD risk using the Steno T1 Risk Engine (SRE) and the Scottish Diabetes Research Network (SDRN) risk prediction models. Risk reduction was determined based on the percent change in risk from baseline between participants receiving dapagliflozin (pooled 5 and 10mg) vs. placebo, and evaluated statistically using a two-factor repeated measures ANOVA.
Results
The relative 10-year estimated CVD risk was significantly lower following 52 weeks of dapagliflozin treatment (SRE: -5.8% [-8.4, -3.3%] & SDRN: -11.9% [-16.1, -7.8%]; ; P<0.01). The 5-year ESKD risk was also significantly lower following 52 weeks of dapagliflozin treatment (SRE: -8.4% [-12.4, -4.4%]; P<0.01). The greatest improvement in ESKD risk was observed at week 56 (-12.8% [-16.6, -9.0%]; P<0.01), in conjunction with an expected rise in eGFR post drug cessation.
Conclusion
Dapagliflozin improves estimated CVD and ESKD risk in T1D participants, emphasizing the need for cardiorenal outcome trials in people living with T1D. By avoiding the acute, reversible GFR “dip” with SGLT2 inhibition, estimation of ESKD risk using models that incorporate GFR may be best performed when drug is discontinued.
Figure 1.