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The impact of sodium-glucose cotransporter-2 inhibitors on breast cancer and cancer-related mortality: a systematic review and meta-analysis of randomized controlled trials

Karimi MA, Khadem R, Haraj A, Farahani MA, Charehsaz Avari Firouzeh P, Azizinezhad A, Raki HK, Belbasi M et al.

BMC cancer, 2025

408,026 participants · 3 citations

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%…

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: 408,026 participants or records.

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