New-onset diabetes with sodium-glucose cotransporter-2 inhibitors in prediabetes: An updated meta-analysis and possible mechanisms.

Background And Aims: A recent systematic review and meta-analysis studied the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on new-onset diabetes (NOD) in adults with prediabetes having chronic kidney disease and heart failure. In light of other large randomized controlled trials (RCTs) of SGLT2i published after this meta-analysis that also reported the NOD outcome in adults with prediabetes, it is of interest to update the NOD outcome with SGLT2i.

Methods: A systemic search in the PubMed and Embase electronic database was made until March 31, 2023, using specific MeSH keywords following PRISMA protocol. Subsequently, we conducted a meta-analysis using the random effects model while applying the inverse variance-weighted averages of pooled logarithmic hazard ratio (HR). Heterogeneity was measured using Higgins I and Cochrane Q statistics and publication bias was evaluated by applying funnel plots. A sensitivity exclusion analysis was additionally made.

Results: This meta-analysis of five RCTs (N = 6752) found a significant reduction in NOD (HR 0.81; 95% CI, 0.69-0.94; P = 0.005) with SGLT2i in adults with prediabetes without any heterogeneity (I = 0%).

Conclusions: SGLT2i has the potential to reduce NOD in adults with prediabetes. Since no effect on HbA1c reduction was seen in adults with prediabetes in all five RCTs included in this meta-analysis, it is conceivable that reduction in NOD is not related to the masking of blood glucose exerted by SGLT2i. However, only an adequately powered trial of SGLT2i in people with prediabetes with a sufficient wash-out period will confirm these findings.