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
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 an...
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2025-06-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14304-8 |
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| author | Mohammad Amin Karimi Razieh Khadem Alireza Haraj Mehdi Azizabadi Farahani Pardis Charehsaz Avari Firouzeh Arash Azizinezhad Hasti Kianpour Raki Mohaddeseh Belbasi Melika Arab Bafrani Niloofar Deravi Yaser Khakpour Ali Faghih Habibi Vahid Aghsaghloo |
| author_facet | Mohammad Amin Karimi Razieh Khadem Alireza Haraj Mehdi Azizabadi Farahani Pardis Charehsaz Avari Firouzeh Arash Azizinezhad Hasti Kianpour Raki Mohaddeseh Belbasi Melika Arab Bafrani Niloofar Deravi Yaser Khakpour Ali Faghih Habibi Vahid Aghsaghloo |
| author_sort | Mohammad Amin Karimi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-309af95849a64ae2b3f39e9dc56284d0 |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-06-01 |
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| series | BMC Cancer |
| spelling | doaj-art-309af95849a64ae2b3f39e9dc56284d02025-08-20T02:05:41ZengBMCBMC Cancer1471-24072025-06-0125111010.1186/s12885-025-14304-8The impact of sodium-glucose cotransporter-2 inhibitors on breast cancer and cancer-related mortality: a systematic review and meta-analysis of randomized controlled trialsMohammad Amin Karimi0Razieh Khadem1Alireza Haraj2Mehdi Azizabadi Farahani3Pardis Charehsaz Avari Firouzeh4Arash Azizinezhad5Hasti Kianpour Raki6Mohaddeseh Belbasi7Melika Arab Bafrani8Niloofar Deravi9Yaser Khakpour10Ali Faghih Habibi11Vahid Aghsaghloo12School of Medicine, Shahid Beheshti University of Medical SciencesStudent Research Committee, Faculty of Medicine, Mashhad University of Medical SciencesFaculty of Medicine, Iran University of Medical SciencesAmol Faculty of Paramedical Sciences, Mazandaran University of Medical SciencesInstitute of Biology and Medicine of Taras, Shevchenko National University of KyivUniversal Scientific Education and Research Network (USERN)Student Research Committee, School of Medicine, Shahid Beheshti University of Medical SciencesStudent Research Committee, School of Pharmacy, Zanjan University of Medical SciencesStudents Scientific Research Center (SSRC), Tehran University of Medical SciencesStudent Research Committee, School of Medicine, Shahid Beheshti University of Medical SciencesFaculty of Medicin, Guilan University of Medical SciencesOtorhinolaryngology Research Center, Department of Otolaryngology and Head and Neck Surgery, School of Medicine, Amiralmomenin Hospital, Guilan University of Medical SciencesOtorhinolaryngology Research Center, Department of Otolaryngology and Head and Neck Surgery, School of Medicine, Amiralmomenin Hospital, Guilan University of Medical SciencesAbstract 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.https://doi.org/10.1186/s12885-025-14304-8SGLT-2iDPP-4iBreast cancerDiabetesMortalityCancer |
| spellingShingle | Mohammad Amin Karimi Razieh Khadem Alireza Haraj Mehdi Azizabadi Farahani Pardis Charehsaz Avari Firouzeh Arash Azizinezhad Hasti Kianpour Raki Mohaddeseh Belbasi Melika Arab Bafrani Niloofar Deravi Yaser Khakpour Ali Faghih Habibi Vahid Aghsaghloo 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 BMC Cancer SGLT-2i DPP-4i Breast cancer Diabetes Mortality Cancer |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | impact of sodium glucose cotransporter 2 inhibitors on breast cancer and cancer related mortality a systematic review and meta analysis of randomized controlled trials |
| topic | SGLT-2i DPP-4i Breast cancer Diabetes Mortality Cancer |
| url | https://doi.org/10.1186/s12885-025-14304-8 |
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