Safety Profile of SGLT-2 Inhibitors in Older Adults: A Systematic Review and Network Meta-Analysis
Abstract
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used in older adults for diabetes, heart failure, and kidney disease. This is the first network meta-analysis focusing on the effects of SGLT2i in older adults.
METHODS: Databases were searched for randomized clinical trials comparing SGLT2i against non-SGLT2i controls or other SGLT2i in relevant populations. Key safety outcomes included acute renal failure (ARF), genital infections, volume depletion, mortality, and serious adverse events (SAEs). Pooled odds ratios (OR) with 95% confidence intervals (CI) were generated using random-effects models for direct and mixed treatment comparisons.
RESULTS: From 97 included trials in the meta-analysis, SGLT2i versus non-SGLT2i were associated with reduced risks of ARF (OR 0.86, 95% CI 0.79-0.94), mortality (OR 0.84, 0.75-0.93), and SAEs (OR 0.84, 0.78-0.89), but increased risks of genital infections (OR 3.32, 2.68-4.12) and volume depletion (OR 1.18, 1.09-1.27). The risk of genital infections was observed more frequently with higher doses (high-dose OR 4.73 vs. low-dose OR 2.90) and escalated sharply with age (≥75 years OR 9.29, 3.13-27.6). The mortality benefit was strongest in adults ≥75 years (OR 0.58, 0.38-0.88). Intra-class analysis revealed distinct safety profiles; for instance, empagliflozin reduced the ARF risk, while sotagliflozin increased the volume depletion risk. Bootstrap and trial sequential analyses confirmed the results' robustness. Grading of…
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