Date of Award
12-1-2025
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Dr. Yi Yang
Second Advisor
Dr. John Bentley
Third Advisor
Dr. Kaustuv Bhattacharya
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Background: Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RA) may improve kidney outcomes in individuals with type 2 diabetes mellitus (T2DM). However, direct head-to-head comparisons of their renal effectiveness with sodium-glucose cotransporter 2 inhibitors (SGLT-2i)—the recommended first-line therapy for older adults with T2DM and chronic kidney disease (CKD)—remain limited.
Objectives: To compare the renal effectiveness of GLP-1RA and SGLT-2i among older adults with T2DM and CKD.
Methods: A new-user, active comparator, matched cohort study was conducted using 5% Medicare data from 2012 to 2020. Older adults (≥65 years) with T2DM and CKD who initiated either a GLP-1RA or an SGLT-2i were identified; the first prescription date was defined as the index date. The 12-month period prior to index served as the baseline. Inclusion criteria required ≥2 outpatient or ≥1 inpatient diagnosis codes for both T2DM and CKD, continuous enrollment in Medicare Parts A, B, and D, and no prior use of GLP-1RA or SGLT-2i during baseline. Propensity score matching was used to balance baseline characteristics, with standardized differences reported pre- and post-matching. Both intention-to-treat and as-treated analyses were conducted. Risk of any CKD progression and end-stage renal disease (ESRD) was assessed using the Fine and Gray model and cumulative incidence functions. As a sensitivity analysis, cohorts were directly matched on baseline CKD stage to assess the robustness of findings.
Results: Between 2013 and 2020, Medicare beneficiaries aged 65 and older initiating GLP-1RA (n=3,967) or SGLT-2i (n=2,443) therapies were included. After 1:1 propensity score matching (n=2,418 per group), GLP-1RA initiators showed a significantly higher risk of CKD progression compared to SGLT-2i initiators in both intention-to-treat (sHR 1.24, 95% CI 1.09–1.41, p<0.001) and as-treated analyses (sHR 1.21, 95% CI 1.02–1.43, p=0.028). For ESRD, GLP-1RA users showed a non-significant trend toward increased risk. Sensitivity analyses with exact matching on baseline CKD stage confirmed these results. No significant interaction by sex was observed.
Conclusion: Among older adults with CKD and T2DM, initiation of SGLT-2i is associated with a lower risk of kidney disease progression compared to GLP-1RA, supporting preferential use of SGLT-2i for kidney protection in this population.
Recommended Citation
Lin, Liang-Yuan, "GLP-1RA VS. SGLT-2I: Preventing Kidney Function Deterioration Among Patients with Type 2 Diabetes and Chronic Kidney Disease" (2025). Electronic Theses and Dissertations. 3521.
https://egrove.olemiss.edu/etd/3521