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Sodium-Glucose Cotransporter 2 Inhibitors and Cancer Risk in Patients With Type 2 Diabetes Mellitus: An Active
Yuhao Li1, Huatang Zeng2,3, Fang Du3
1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Key Laboratory of Epidemiology of Major Diseases, Ministry of Education, Beijing, China.
International Journal of Cancer
|August 1, 2026
Summary
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) show a reduced risk of overall cancer in type 2 diabetes mellitus patients compared to DPP-4 inhibitors. SGLT-2i also lowered lung and thyroid cancer risks, suggesting potential cancer prevention benefits.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- The relationship between sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cancer risk in type 2 diabetes mellitus (T2DM) patients is debated.
- Previous studies have yielded conflicting results regarding the oncogenic potential of SGLT-2i.
Purpose of the Study:
- To investigate the association between SGLT-2i use and the risk of overall and site-specific cancers in T2DM patients.
- To compare cancer risk between SGLT-2i users and users of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA).
Main Methods:
- A target trial emulation with an active-comparator, new-user design was conducted using the Shenzhen Public Health Data Platform.
- 134,481 T2DM patients were included, comparing SGLT-2i users with DPP-4i users, and a separate cohort compared SGLT-2i with GLP-1RA users.
- Overlapping weighting-based Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for confounders.
Main Results:
- SGLT-2i use was associated with a significantly lower risk of overall cancer compared to DPP-4i (HR: 0.91; 95% CI: 0.85-0.98).
- A reduced risk was observed for lung (HR: 0.84; 95% CI: 0.72-0.98) and thyroid cancers (HR: 0.76; 95% CI: 0.61-0.96) with SGLT-2i compared to DPP-4i.
- No significant difference in overall cancer risk was found between SGLT-2i and GLP-1RA users (HR: 1.03; 95% CI: 0.85-1.25).
Conclusions:
- SGLT-2i use is associated with a reduced risk of overall, lung, and thyroid cancers compared to DPP-4i in T2DM patients.
- The findings support the safety of SGLT-2i concerning carcinogenic risk in T2DM patients.
- SGLT-2i may hold potential in cancer prevention strategies for individuals with type 2 diabetes mellitus.
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