SGLT2 Inhibitors Carry 40% Higher DKA Risk Than GLP-1 Drugs in Kidney Disease Patients | Research

The takeaway

In 143,858 matched CKD+T2D patients, SGLT2 inhibitor initiation was associated with 40% higher DKA hospitalization risk vs GLP-1 RA initiation (HR 1.40), consistent across all subgroups.

40% higher DKA risk
SGLT2 inhibitors carried significantly higher diabetic ketoacidosis risk than GLP-1 drugs in kidney disease patients across all subgroups

What the researchers found

SGLT2i vs GLP-1RA: DKA IR 4.37 vs 3.13 per 1,000 person-years; HR 1.40 (95% CI 1.16-1.68); NNH 813; consistent across age, sex, BMI, frailty, CVD, retinopathy, metformin, and insulin subgroups.

Why it matters

DKA in diabetic kidney patients can be fatal. Knowing GLP-1 drugs carry lower DKA risk than SGLT2 inhibitors informs safer prescribing.

How the study worked

Population-based new-user active comparator study across 3 US databases (Optum, MarketScan, Medicare), 1:1 propensity matching, 143,858 patients total.

What this study cannot tell us

Observational design. DKA identified by ICD codes which may undercount. Cannot determine optimal management after DKA diagnosis.

How to read the evidence

Large multi-database propensity-matched study with consistent subgroup results. Strong real-world evidence.

When this study was published

Published in 2025 using data through 2024.

The bigger picture

As both drug classes expand to CKD, comparative safety data like this is essential for optimal drug selection in this high-risk population.

Questions still open

Should GLP-1 drugs be preferred over SGLT2i in CKD patients at high DKA risk?
Are there specific patient factors predicting higher SGLT2i DKA risk?
Would combining low-dose SGLT2i with GLP-1 RA mitigate DKA risk?

Common questions

Is DKA common with SGLT2 inhibitors?

Overall rates are low (4.37 per 1,000 patients per year), but it is 40% more likely than with GLP-1 drugs. Patients with kidney disease should be monitored for DKA symptoms.

Should kidney patients avoid SGLT2 inhibitors?

Not necessarily — they have important kidney benefits. But this study suggests GLP-1 drugs may be the safer first choice when DKA risk is a concern, with SGLT2 inhibitors added with appropriate monitoring.

Read the original research

Diabetic Ketoacidosis Risk in Sodium-Glucose Cotransporter-2 Inhibitors vs Glucagon-Like Peptide-1 Receptor Agonists Initiators with CKD Stages 3-4 and Type 2 Diabetes.

Kidney360

View on PubMed ↗Publisher’s paper ↗

Citation

Hansrivijit, Panupong; Patorno, Elisabetta; Tesfaye, Helen; Wexler, Deborah J; Paik, Julie M. (2026). Diabetic Ketoacidosis Risk in Sodium-Glucose Cotransporter-2 Inhibitors vs Glucagon-Like Peptide-1 Receptor Agonists Initiators with CKD Stages 3-4 and Type 2 Diabetes.. Kidney360. https://doi.org/10.34067/KID.0000001144