Abstract
BACKGROUND: SGLT-2 inhibitors (SGLT-2i) lower blood glucose levels in type 2 diabetes by inhibiting renal glucose reabsorption. While the relationship between SGLT-2i and breast cancer remains inconclusive, emerging evidence suggests potential anticancer properties. This systematic review and meta-analysis compares the effects of SGLT-2i and DPP-4i on breast cancer incidence and related mortality to clarify current conflicting evidence. METHODS: An extensive literature search was conducted using MeSH terms and relevant keywords related to SGLT-2 inhibitors, breast cancer, and mortality across PubMed, Scopus, and Google Scholar up to August 12, 2023. Additionally, reference lists of the included studies were manually screened to identify further eligible articles. Data on the impact of SGLT-2 inhibitors on breast cancer and its associated mortality were extracted from the included studies. Findings were presented using hazard ratios (HR) with 95% confidence intervals (CI) displayed in a forest plot. At the same time, heterogeneity was assessed using the I² statistic, applying a random-effects model for significant heterogeneity. RESULTS: Seven cohort studies involving 408,026 individuals were included. SGLT-2 inhibitors were not associated with a significant difference in breast cancer risk compared to DPP-4 inhibitors (HR = 1.03, 95% CI: 0.82-1.30, p > 0.05), but were linked to a 30% reduction in breast cancer-specific mortality and improved overall survival (HR = 0.71, 95% CI: 0.65-0.77, p < 0.05). CONCLUSIONS: The impact of SGLT-2 inhibitors and DPP-4 inhibitors on breast cancer incidence appears to be comparable. However, SGLT-2 inhibitors may confer a greater reduction in breast cancer-related mortality and potentially improve overall patient survival compared to DPP-4 inhibitors. Given the observed heterogeneity among existing studies, larger, high-quality randomized controlled trials are warranted to validate these findings.