Risk of Diabetic Ketoacidosis Associated with Sodium Glucose Cotransporter-2 Inhibitors: A Network Meta-Analysis and Meta-Regression
Abstract
Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) represent an emerging class of drugs with diverse indications. Despite their therapeutic potential, concerns regarding safety, particularly diabetic ketoacidosis (DKA), remain contentious, with uncertainty regarding differences among various SGLT2is. This study aimed to conduct a network meta-analysis and meta-regression to evaluate the risk of SGLT2i-induced DKA and associated factors. Methods: We systematically searched electronic databases for randomized clinical trials assessing SGLT2is across indications, reporting incidences of DKA. Mixed treatment comparison pooled estimates (MTCPEs) were calculated, and odds ratios (OR) with 95% confidence intervals (95% CI) served as effect estimates. We analyzed differences across dose categories (low, medium, and high) and conducted a meta-regression analysis to identify risk factors. The strength of evidence for key comparisons was determined. Results: Our analysis included 73 articles encompassing 85,997 participants assessing the risk of DKA. SGLT2is were associated with a heightened risk of DKA compared to placebo/control interventions (OR: 1.83; 95% CI: 1.35, 2.46), a finding confirmed by bootstrap analysis. Among SGLT2is, dapagliflozin (OR: 1.9; 95% CI: 1.17, 3.08), sotagliflozin (OR: 1.93; 95% CI: 1.14, 3.25), canagliflozin (OR: 1.11; 95% CI: 1.11, 12.45), and ertugliflozin (OR: 3.92; 95% CI: 1.04, 14.77) exhibited increased DKA risk. No significant differences…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 85,997 participants or records.
Read the paper
Related studies
- Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials
- Efficacy of personalized psychological interventions: A systematic review and meta-analysis
- Effects of Lifestyle Interventions That Include a Physical Activity Component in Class II and III Obese Individuals: A Systematic Review and Meta-Analysis
- Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis
- Topical treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials
- Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.