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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author Hamed Hajishah
Parsa Mazloom
Amirhossein Salehi
Danial Kazemi
Reza Samiee
Hossein Majlesi
Mohammad Javad Amini
Arefeh Meyari
Negin Safari Dehnavi
Masood Zangi
author_facet Hamed Hajishah
Parsa Mazloom
Amirhossein Salehi
Danial Kazemi
Reza Samiee
Hossein Majlesi
Mohammad Javad Amini
Arefeh Meyari
Negin Safari Dehnavi
Masood Zangi
author_sort Hamed Hajishah
collection DOAJ
description 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.
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spelling doaj-art-543a84f929bc4b44b1c6a80d710837f02025-08-20T03:46:23ZengBMCDiabetology & Metabolic Syndrome1758-59962025-08-0117111310.1186/s13098-025-01898-zComparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysisHamed Hajishah0Parsa Mazloom1Amirhossein Salehi2Danial Kazemi3Reza Samiee4Hossein Majlesi5Mohammad Javad Amini6Arefeh Meyari7Negin Safari Dehnavi8Masood Zangi9Student Research Committee, Tehran Medical Sciences Branch, Islamic Azad UniversityStudent Research Committee, Tehran Medical Sciences Branch, Islamic Azad UniversityStudent research committee, School of medicine, Shahid Beheshti Medical UniversityStudent Research Committee, Isfahan University of Medical SciencesSchool of Medicine, Tehran University of Medical ScienceSchool of medicine, Shahid Beheshti Medical UniversityStudent Research Committee, Medical School, Alborz University of Medical SciencesSchool of medicine, Shahid Beheshti Medical UniversitySchool of Medicine, Tehran University of Medical ScienceCritical Care Quality Improvement Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical SciencesAbstract 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.https://doi.org/10.1186/s13098-025-01898-zSodium-Glucose transporter 2 inhibitorsDipeptidyl-Peptidase IV inhibitorsDiabetes mellitus, type 2Neoplasms
spellingShingle Hamed Hajishah
Parsa Mazloom
Amirhossein Salehi
Danial Kazemi
Reza Samiee
Hossein Majlesi
Mohammad Javad Amini
Arefeh Meyari
Negin Safari Dehnavi
Masood Zangi
Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis
Diabetology & Metabolic Syndrome
Sodium-Glucose transporter 2 inhibitors
Dipeptidyl-Peptidase IV inhibitors
Diabetes mellitus, type 2
Neoplasms
title Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis
title_full Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis
title_fullStr Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis
title_full_unstemmed Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis
title_short Comparative risk of cancer associated with SGLT inhibitors and DPP-4 inhibitors in patients with diabetes: a systematic review and meta-analysis
title_sort comparative risk of cancer associated with sglt inhibitors and dpp 4 inhibitors in patients with diabetes a systematic review and meta analysis
topic Sodium-Glucose transporter 2 inhibitors
Dipeptidyl-Peptidase IV inhibitors
Diabetes mellitus, type 2
Neoplasms
url https://doi.org/10.1186/s13098-025-01898-z
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