Does baseline glycemic control influence the likelihood of diabetic ketoacidosis (DKA) with sodium–glucose co-transporter 2 inhibitor (SGLT2i) therapy in type 2 diabetes mellitus (T2DM)? A systematic review and meta-analysis published in Diabetes, Obesity and Metabolism indicates that higher baseline glycated hemoglobin (HbA1c) levels may be associated with greater DKA risk, particularly in real-world settings.

The analysis included 22 studies, comprising 15 observational cohorts and 7 randomized controlled trials. Data were identified from MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and reference sources up to January 2026. Adults with T2DM receiving SGLT2 inhibitors were compared with placebo or other therapies. Risk ratios (RRs) for DKA were pooled and analyzed based on baseline HbA1c categories. Meta-regression was performed to evaluate whether HbA1c modified the observed risk.

In observational studies, SGLT2i use was associated with higher DKA risk among individuals with elevated HbA1c (RR 1.63; 95% CI 1.46-1.81). No significant increase was observed at lower HbA1c levels (RR 1.10; 95% CI 0.80-1.51). The interaction between HbA1c and DKA risk was statistically significant (P=0.018). In randomized trials, DKA risk estimates were higher in both HbA1c groups, but no significant interaction was detected (P=0.73). Elevated HbA1c remained independently associated with DKA among SGLT2i users (RR 1.50; 95% CI 1.17-1.92).

These findings suggest that baseline HbA1c may influence DKA risk with SGLT2 inhibitors. However, variation in HbA1c ranges across studies limits firm conclusions.