Comparative Effectiveness of SGLT2 Inhibitor and GLP-1 Receptor Agonist on Kidney and Cardiovascular Outcomes by...

Area of Science:

• Endocrinology
• Nephrology
• Cardiology

Background:

• Direct comparisons between non-exendin glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) for kidney failure or cardiovascular-kidney-metabolic (CKM) composite endpoints are limited.
• Understanding if baseline kidney failure risk influences the comparative effectiveness of GLP-1 RA versus SGLT2i is crucial for clinical decision-making in type 2 diabetes management.

Purpose of the Study:

• To compare the effectiveness of SGLT2 inhibitors and non-exendin GLP-1 receptor agonists in a large cohort of veterans with type 2 diabetes.
• To investigate whether the Kidney Failure Risk Equation (KFRE) score modifies the comparative effectiveness of these drug classes on kidney and cardiovascular outcomes.

Main Methods:

• A national veterans cohort with type 2 diabetes initiating SGLT2i, non-exendin GLP-1 RA, or insulin glargine was established.
• Inverse probability of treatment weighting was used to balance baseline characteristics before comparing outcomes including kidney failure, major adverse cardiac events (MACE), and CKM composite endpoints.
• Effect modification by KFRE score was tested for comparative drug effectiveness.

Main Results:

• Compared to GLP-1 RA, SGLT2i users showed a trend toward lower kidney failure risk but a higher risk of MACE and the CKM composite.
• The comparative effectiveness of SGLT2i versus GLP-1 RA significantly differed between moderate-risk (2-6% KFRE) and high-risk (≥6% KFRE) subgroups for most outcomes.
• GLP-1 RA demonstrated greater protection for kidney failure, MACE, and CKM composite in the moderate-risk KFRE group, whereas SGLT2i showed greater benefit in the high-risk KFRE group.

Conclusions:

• SGLT2i and GLP-1 RA have comparable mortality risks, with SGLT2i potentially offering a lower kidney failure risk but a modestly higher cardiovascular event risk than GLP-1 RA.
• The choice between SGLT2i and GLP-1 RA should consider individual patient's kidney failure risk, as GLP-1 RA appears more beneficial for moderate risk and SGLT2i for high risk.