Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis

Abstract Aims This systematic review and meta-analysis aimed to compare the overall and site-specific cancer risk associated with SGLT2i versus DPP4i in patients with type 2 diabetes mellitus. Methods We systematically searched PubMed, Scopus, and Web of Science for cohort studies comparing cancer i...

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Main Authors: Hamed Hajishah, Parsa Mazloom, Amirhossein Salehi, Danial Kazemi, Reza Samiee, Hossein Majlesi, Mohammad Javad Amini, Arefeh Meyari, Negin Safari Dehnavi, Masood Zangi
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Diabetology & Metabolic Syndrome
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Online Access:https://doi.org/10.1186/s13098-025-01898-z
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Summary:Abstract Aims This systematic review and meta-analysis aimed to compare the overall and site-specific cancer risk associated with SGLT2i versus DPP4i in patients with type 2 diabetes mellitus. Methods We systematically searched PubMed, Scopus, and Web of Science for cohort studies comparing cancer incidence in adult type 2 diabetes patients treated with SGLT2i versus DPP4i. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model due to significant heterogeneity (I²). Subgroup analyses by cancer type and publication bias assessment were performed. Results Seventeen cohort studies met the inclusion criteria. Overall, SGLT2i use was associated with a significantly lower risk of incident cancer compared to DPP4i use (Pooled RR = 0.77, 95%CI:0.70–0.84; I²=81.6%). Subgroup analyses revealed significantly lower risks for liver (RR = 0.76), lung (RR = 0.87), and prostate (RR = 0.75) cancers with SGLT2i. Trends towards lower risk were observed for colorectal (RR = 0.80) and stomach (RR = 0.69) cancers. No significant differences were found for bladder, breast, or pancreatic cancer risk. Conclusion This meta-analysis suggests that SGLT2 inhibitors are associated with a reduced overall risk of cancer compared to DPP-4 inhibitors in patients with type 2 diabetes mellitus, particularly for liver, lung, and prostate cancers. However, these findings are based on observational data with significant heterogeneity and varying follow-up times, requiring additional long-term research to confirm.
ISSN:1758-5996