SGLT2 inhibitors and risk of cancer in type 2 diabetes: A systematic review and meta-analysis of randomised controlled trials
Open accessAbstract
Aims/hypothesis The association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes.Methods We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs.Results In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]).Conclusions/interpretation Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.
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Modest survival benefits with metformin have been reported for breast, ovarian, endometrial, prostate, lung, kidney, liver, and earlier stage pancreatic cancers.
“Modest survival benefits also have been reported for breast, ovarian, endometrial, prostate, lung, kidney, liver, and earlier stage pancreatic cancers.1791–1800”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1797]
The Discussion and Results passages examine SGLT2 inhibitors and cancer incidence, not survival after cancer diagnosis. Searches for metformin survival benefits and pancreatic cancer survival found no passage reporting the claimed benefits for the listed cancers; the metformin mentions concern background diabetes treatment. (LLM, conf=0.76)
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- Authors
- Tang, H., Dai, Q., Shi, W., Zhai, S., Song, Y., & Han, J.
- Affiliations
- Peking University Third Hospital (CN)
- Vanderbilt University (US)
- Indiana University Indianapolis (US)
- Corresponding author
- Song, Yiqing
- Han, Jiali
- Venue
- Diabetologia
- Published
- 2017-07-19
- Volume
- 60
- Issue
- 10
- Pages
- 1862-1872
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2739126694
- Cited by
- 206
- References
- 79
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 37 · 2023: 23 · 2022: 27 · 2021: 15 · 2020: 16 · 2019: 30 · 2018: 11 · 2017: 5 · 2015: 1
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- Indiana University Health–Indiana University School of Medicine Strategic Research Initiative
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- SGLT2 inhibitors, type 2 diabetes, cancer risk, bladder cancer, empagliflozin, canagliflozin, gastrointestinal cancer, drug safety, glucose-lowering agents
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Glucosides, Humans, Hypoglycemic Agents, Neoplasms, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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