Abstract: TH-PO0369
Fragility Index of SGLT2 Inhibitor, GLP-1 Receptor Agonist, and Nonsteroidal Mineralocorticoid Receptor Antagonist (nsMRA) Clinical Trials for Kidney and Cardiovascular Protection
Session Information
- Diabetic Kidney Disease: From Early Biomarkers to Novel Therapeutic Targets
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Sankar Dass, Sarvesh, Fort Bend Independent School District, Sugar Land, Texas, United States
- Nambi, Abhinav, Fort Bend Independent School District, Sugar Land, Texas, United States
- Abushamat, Layla A, Baylor College of Medicine, Houston, Texas, United States
- Gregg, Lucile Parker, Baylor College of Medicine, Houston, Texas, United States
Background
Sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) have demonstrated kidney and cardiovascular (CV) benefits in clinical trials. The fragility index (FI) is the minimum number of participants whose outcome would need to change from a non-event to an event for a statistically significant trial result to become non-significant. We described FI for trials of kidney and CV benefits of SGLT2is, GLP1RAs, and nsMRAs.
Methods
Clinical practice guidelines and MEDLINE were used to identify large randomized, placebo-controlled clinical trials for the three medication classes of interest. We calculated FI for the composite kidney outcome measure and composite kidney/CV outcome data reported in the individual trials using clincalc.com. Higher FI scores indicate less fragile trial results. Studies with a non-significant result were assigned an FI of 0.
Results
We included 9 trials of SGLT2i, 7 trials of GLP-1RA, and 3 trials of nsMRA. FI for composite kidney outcomes in SGLT2i trials ranged from 0 to 71, with a median of 22 and a mean of 30 (Figure). The FI was numerically higher for trials conducted among a CKD population than those enrolling people with and without CKD (mean FI 40 vs 20, respectively). FI for GLP-1RA trials ranged from 0 to 45, with a median of 12 and a mean of 13. FI for the FLOW trial conducted in a CKD population increased from 3 to 31 when adding CV death to the composite kidney outcome. FI for FIDELIO-DKD was 35, but 0 for the other nsMRA trials.
Conclusion
SGLT2i trials that enrolled CKD populations generally had higher FIs than trials enrolling people with and without CKD. These data support guideline recommendations for the use of these agents and emphasize the need for dedicated studies of novel cardiometabolic interventions in CKD populations to inform treatment guidelines effectively. Future studies may examine FI for other interventions to assess the strength of evidence for treatments in people with kidney diseases.
Funding
- Veterans Affairs Support