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

Abstract

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.