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SGLT2i vs GLP-1RA: Kidney Risk Level Determines Which Drug Works Better

RPEP-152642026Hartsell, Sydney E; Wei, Guo; Singh, Ravinder; Throolin, Michael; Nevers, McKenna R; Sarwal, Amara; Derington, Catherine G; Curtis, Christa; Boucher, Robert E; Shen, Jincheng; Drakos, Stavros; Greene, Tom; Beddhu, Srinivasan
evidence
The takeaway

In 160,428 veterans with T2D, SGLT2i were more kidney-protective at high kidney failure risk while GLP-1 RAs were more cardioprotective at moderate risk, with KFRE score guiding optimal therapy.

Risk level decides

At moderate kidney risk, GLP-1 drugs were better. At high kidney risk, SGLT2 inhibitors were better. The kidney failure risk equation guides the choice.

What the researchers found

SGLT2i vs GLP-1 RA: kidney failure HR trending lower for SGLT2i (0.89); MACE higher with SGLT2i (HR 1.14). KFRE modified effects: GLP-1 RA better at moderate risk; SGLT2i better at high kidney failure risk.

Why it matters

Personalizing drug choice based on kidney failure risk could prevent both kidney failure and cardiovascular events more effectively than one-size-fits-all prescribing.

How the study worked

Population-based new-user active comparator cohort study of 160,428 veterans (53% SGLT2i, 14% GLP-1 RA, 34% glargine) with IPTW and KFRE-stratified analyses through March 2023.

What this study cannot tell us

Observational veteran cohort (predominantly male). Non-exendin GLP-1 RAs only. Residual confounding possible. Cannot determine if results extend to non-veteran populations.

How to read the evidence

Large population-based comparative effectiveness study with sophisticated risk stratification. Strongest non-RCT evidence available for this question.

When this study was published

Published in 2025.

The bigger picture

This establishes kidney failure risk as a practical clinical tool for choosing between the two most important diabetes drug classes.

Questions still open

  • Should KFRE scoring guide drug selection in clinical practice?
  • Would combining SGLT2i and GLP-1 RA provide benefits across all risk levels?
  • Does the kidney risk modification apply to tirzepatide?

Common questions

Should I take SGLT2 inhibitor or GLP-1 drug for my diabetes?
This study suggests it depends on your kidney health. If your kidneys are at moderate risk, GLP-1 drugs may be better. If kidney risk is high, SGLT2 inhibitors appear superior. Your doctor can calculate your risk score.
What is KFRE?
The Kidney Failure Risk Equation estimates how likely your kidneys are to fail. This study shows it can guide which diabetes drug will work best for you.

Read the original research

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

Journal of the American Society of Nephrology : JASN

View on PubMed ↗Publisher’s paper ↗

Citation

Hartsell, Sydney E; Wei, Guo; Singh, Ravinder; Throolin, Michael; Nevers, McKenna R; Sarwal, Amara; Derington, Catherine G; Curtis, Christa; Boucher, Robert E; Shen, Jincheng; Drakos, Stavros; Greene, Tom; Beddhu, Srinivasan. (2026). Comparative Effectiveness of SGLT2 Inhibitor and GLP-1 Receptor Agonist on Kidney and Cardiovascular Outcomes by Kidney Failure Risk.. Journal of the American Society of Nephrology : JASN. https://doi.org/10.1681/ASN.0000001016