Kidney360Feb 2, 2026

Risk of Diabetic Ketoacidosis in People with Moderate to Severe Kidney Disease and Type 2 Diabetes Starting SGLT2 Inhibitors Compared to GLP-1 Receptor Agonists

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Among patients with CKD stages 3-4 and type 2 diabetes, SGLT2 inhibitor initiation was associated with a higher but still low absolute rate of DKA hospitalization than GLP-1RA initiation.

Evidence

This population-based new-user active-comparator cohort study across three U.S. healthcare databases included 143,858 propensity-matched patients and found DKA hospitalization rates of 4.37 vs. 3.13 events per 1,000 person-years for SGLT2i versus GLP1RA initiators (HR 1.40; 95% CI 1.16-1.68).

Caveat

The evidence is observational claims-database evidence, so residual confounding and outcome coding limits remain despite matching and subgroup analyses.

Simplified

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are effective in managing chronic kidney disease (CKD) and type 2 diabetes (T2D). However, there are concerns about an increased risk of diabetic ketoacidosis (DKA) associated with the use of SGLT2i, particularly in patients with CKD.

METHODS: The is a population-based, new-user, active comparator cohort study comparing SGLT2i vs. GLP1RA initiators using three U.S. healthcare databases: Optum's de-identified Clinformatics® Data Mart (2014-2024), Merative MarketScan (2014-2022), and Medicare Fee-for-Service (2014-2020). The exposure is initiation of either SGLT2i or GLP1RA, defined as a new prescription without prior use in 365 days. The primary outcome was hospitalization with DKA identified via inpatient ICD-9/10 codes. Incidence rates (IRs), rate differences (RDs), and hazard ratios (HRs) were calculated.

RESULTS: After 1:1 propensity score matching, the study population included 143,858 patients, 71,929 in the SGLT2i arm and 71,929 in the GLP1RA arm. The mean age (standard deviation) was 71.28 (8.16) years, and 48.8% were female. Patients initiating SGLT2i had higher risk of hospitalization with DKA compared to GLP1RA initiators (IR 4.37 vs. 3.13 events per 1,000 person-years; RD 1.23 [95% CI 0.54, 1.92]; HR 1.40 [95% CI 1.16, 1.68]). The number needed to harm was 813 per 1,000 person-years for SGLT2i compared to GLP1RA initiation. Results remained consistent in subgroup analyses stratified by age (<70 vs. ≥70 years), sex, body mass index (<30 vs. ≥30 kg/m2), frailty status, baseline cardiovascular disease, diabetic retinopathy, hyperglycemia, metformin use, and insulin use.

CONCLUSIONS: The incidence rate of DKA among SGLT2i and GLP1RA initiators remained low overall. However, SGLT2i use was associated with a 40% increased risk of hospitalization with DKA compared to GLP1RA use among patients with CKD stages 3-4 and T2D. Clinicians should remain vigilant when monitoring patients with CKD and T2D treated with SGLT2i.