Interrelationship Between Baseline HbA1c , SGLT ‐2 Inhibitor Use and Risk of Diabetic Ketoacidosis in Adults With Type 2 Diabetes: A Systematic Review and Meta‐Analysis
Authors' conclusion
SGLT-2i use is associated with an increased risk of DKA in adults with T2D, with a higher risk observed in those with elevated baseline HbA1c, particularly in real-world settings. However, the narrow range of HbA1c values across studies limits definitive conclusions, and further research is warranted.
Study context
- Population
- Adults with T2D in studies reporting baseline HbA1c and diabetic ketoacidosis (DKA) events; searches to January 202622 studies (15 cohorts, 7 RCTs)
- Comparison
- SGLT2i vs placebo or active comparators, stratified by baseline HbA1c
- Outcome
- DKA risk by baseline HbA1c
Methodological detailsrandom-effects meta-regression, stratified by baseline HbA1c
- Random-effects meta-regression
- Stratified by baseline HbA1c
Pooled result
As reported in the abstract
DKA risk stratified by baseline HbA1c (high vs low)
- Observational studies, elevated HbA1c: RR
- 1.63 (1.46-1.81) (95% CI)
- Observational studies, lower HbA1c: RR
- 1.10 (0.80-1.51) (CI)
- Observational studies: significant effect modification
- p = 0.018
- RCTs, high HbA1c: pooled RR
- 2.37 (1.44-3.90) (CI)
- RCTs, low HbA1c: pooled RR
- 2.01 (0.84-4.79) (CI)
- RCTs: no significant interaction
- p = 0.73
Further pooled results
Elevated HbA1c and DKA among SGLT2i users
- Elevated HbA1c independently associated with DKA, RR
- 1.50 (1.17-1.92)
Evidence certainty
- Evidence certainty ranged from high to low
Original publication
Interrelationship Between Baseline HbA1c , SGLT ‐2 Inhibitor Use and Risk of Diabetic Ketoacidosis in Adults With Type 2 Diabetes: A Systematic Review and Meta‐Analysis. Diabetes Obes Metab. Published 7 April 2026. doi:10.
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