Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists and Sodium/Glucose Cotransporter 2 Inhibitors in Preventing Chronic Kidney Failure and Mortality in Patients With Type 2 Diabetes and CKD

Abstract

Rationale & Objective

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular, kidney, and survival outcomes in patients with type 2 diabetes; however, the comparative effectiveness of these drugs in a real-world setting remains unclear.

Study Design

Retrospective cohort study.

Setting & Participants

79,047 patients with type 2 diabetes and an estimated glomerular filtration rate <60 mL/min/1.73 m² in the Taiwan National Health Insurance Research Database between 2016 and 2021.

Exposure

Treatment with GLP-1RAs or SGLT2 inhibitors.

Outcome

Initiation of kidney replacement therapy (KRT) and all-cause mortality.

Analytic Approach

Propensity score matching was performed to balance baseline characteristics between the groups. Cox proportional hazards models were used to estimate HRs and 95% CIs for each outcome using an intention-to-treat approach.

Results

14,182 (7,091 initiating GLP-1RAs and 7,091 initiating SGLT2 inhibitors) individuals among the original cohort of 79,047 were included in the propensity score–matched analysis. With a median follow-up duration of 2.5 years, people initiating GLP-1RAs had a higher risk of requiring KRT than those initiating SGLT2 inhibitors (HR, 1.39; 95% CI, 1.19-1.63). Although tests of interaction did not have statistically significant findings, stratified analyses suggested possibly greater differences between the 2 drugs among patients with an estimated glomerular filtration rate <45 mL/min/1.73 m² or a urine albumin-creatinine ratio >300 mg/g. Overall mortality did not differ between treatment groups.

Limitations

Nonrandomized treatment selection.

Conclusions

Patients receiving SGLT2 inhibitors exhibited lower rates of progression to KRT than those receiving GLP-1RAs. These findings may inform the choice of these therapies in the setting of chronic kidney disease and type 2 diabetes.

Plain-Language Summary

Chronic kidney disease is a major complication of type 2 diabetes that often leads to kidney failure and increased mortality. This study aimed to compare the effectiveness of 2 drug classes, glucagon-like peptide-1 receptor agonists and sodium/glucose cotransporter 2 inhibitors, in preventing kidney failure and death in patients with type 2 diabetes and chronic kidney disease. Using a nationwide health database in Taiwan, we applied rigorous statistical methods to balance differences between treatment groups and analyze outcomes. Our findings demonstrated that sodium/glucose cotransporter 2 inhibitors might be more effective than glucagon-like peptide-1 receptor agonists in reducing the risk of kidney failure, and possibly even more so in patients with advanced kidney disease. These results may inform the choice of these agents in the setting of chronic kidney disease and diabetes.