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Association between sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis of

Bo Xu1,2,3,4,5, Bo Kang1,2,3,4, Shaoqian Li1,2,3,4,6

  • 1The First Affiliated Hospital, Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

International Journal of Clinical Pharmacy
|April 28, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed neutral overall cancer risk in type 2 diabetes mellitus patients. However, SGLT2 inhibitors may reduce gastrointestinal cancer risk compared to metformin.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • The impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer incidence relative to other glucose-lowering medications is not well-established.
  • Understanding this association is crucial for optimizing diabetes management and patient safety.

Purpose of the Study:

  • To conduct a systematic review and meta-analysis.
  • To investigate the association between SGLT2 inhibitors and cancer risk compared to active comparators in patients with type 2 diabetes mellitus.

Main Methods:

  • Systematic literature search across major databases (Web of Science, PubMed, ClinicalTrials.gov) up to March 11, 2024.
  • Inclusion of trials with a minimum follow-up of 52 weeks.
  • Meta-analysis using the Mantel-Haenszel method with risk ratios (RR) and 95% confidence intervals (CI).

Main Results:

  • Analysis of 20 trials involving 16,399 patients with type 2 diabetes mellitus.
  • Overall cancer risk associated with SGLT2 inhibitors was neutral (RR 1.00; 95% CI 0.71-1.40) with moderate evidence certainty.
  • No significant impact on breast, endometrial, gastrointestinal, prostate, renal, or respiratory cancers; however, a significant reduction in gastrointestinal cancer risk was observed with SGLT2 inhibitors versus metformin (RR 0.23; 95% CI 0.06-0.95).

Conclusions:

  • SGLT2 inhibitors demonstrate a neutral overall cancer risk profile in patients with type 2 diabetes mellitus.
  • A potential benefit of reduced gastrointestinal cancer risk exists when SGLT2 inhibitors are compared to metformin.
  • Findings support personalized therapy selection based on individual patient risk profiles.
Keywords:
CancerGastrointestinal cancerMeta-analysisSodium-glucose cotransporter 2 inhibitors

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