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Background <p>The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer incidence compared to other hypoglycemic drugs remains unclear.</p> Aim <p>This systematic review and meta-analysis was designed to investigate the association of SGLT2 inhibitors with cancer compared to active comparators.</p> Method <p>A systematic search was conducted up to March 11, 2024 across Web of Science, PubMed, and ClinicalTrials.gov, and included trials with a follow-up period of at least 52&#xa0;weeks. The Mantel–Haenszel statistical method was utilized, applying risk ratio (RR) and 95% confidence intervals (CI) for binary variables.</p> Results <p>Twenty trials covering 16,399 type 2 diabetes mellitus patients were included. Median follow-up duration was 1.0 (1.0) years. The effect of SGLT2 inhibitors on the overall risk of cancer was neutral compared to active comparators (RR 1.00; 95%CI 0.71–1.40; <i>p</i> = 0.99; moderate certainty of evidence). SGLT2 inhibitors did not have a significant impact on breast cancer, endometrial/uterine cancer, gastrointestinal cancer, prostate cancer, renal cancer, or respiratory cancer. Subgroup analysis indicated a significant reduction in the risk of gastrointestinal cancer with SGLT2 inhibitors compared to metformin (RR 0.23; 95%CI 0.06–0.95; <i>p</i> = 0.04). SGLT2 inhibitors potentially increased gastrointestinal cancer risk relative to sulfonylureas (RR 3.52; 95%CI 0.91–13.64; <i>p</i> = 0.07).</p> Conclusion <p>SGLT2 inhibitors showed neutral cancer risk in T2DM patients but may reduce gastrointestinal cancer versus metformin, guiding tailored therapy based on patient risk profiles.</p>

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

  • 期刊论文

  • 发表日期：

    2025年4月28日

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  • Bo Xu,
  • Bo Kang,
  • Shaoqian Li,
  • Jixiang Chen,
  • Jiecan Zhou

摘要

Background

The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer incidence compared to other hypoglycemic drugs remains unclear.

Aim

This systematic review and meta-analysis was designed to investigate the association of SGLT2 inhibitors with cancer compared to active comparators.

Method

A systematic search was conducted up to March 11, 2024 across Web of Science, PubMed, and ClinicalTrials.gov, and included trials with a follow-up period of at least 52 weeks. The Mantel–Haenszel statistical method was utilized, applying risk ratio (RR) and 95% confidence intervals (CI) for binary variables.

Results

Twenty trials covering 16,399 type 2 diabetes mellitus patients were included. Median follow-up duration was 1.0 (1.0) years. The effect of SGLT2 inhibitors on the overall risk of cancer was neutral compared to active comparators (RR 1.00; 95%CI 0.71–1.40; p = 0.99; moderate certainty of evidence). SGLT2 inhibitors did not have a significant impact on breast cancer, endometrial/uterine cancer, gastrointestinal cancer, prostate cancer, renal cancer, or respiratory cancer. Subgroup analysis indicated a significant reduction in the risk of gastrointestinal cancer with SGLT2 inhibitors compared to metformin (RR 0.23; 95%CI 0.06–0.95; p = 0.04). SGLT2 inhibitors potentially increased gastrointestinal cancer risk relative to sulfonylureas (RR 3.52; 95%CI 0.91–13.64; p = 0.07).

Conclusion

SGLT2 inhibitors showed neutral cancer risk in T2DM patients but may reduce gastrointestinal cancer versus metformin, guiding tailored therapy based on patient risk profiles.