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Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis

B Xu1,2,3,4,5, B Kang1,2,3,4, S 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.

Journal of Endocrinological Investigation
|March 26, 2024
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors did not increase overall cancer risk, but did increase renal cancer risk. Dapagliflozin reduced bladder and respiratory cancer risks, while ertugliflozin increased overall cancer incidence.

Area of Science:

  • Oncology
  • Pharmacology
  • Cardiology
  • Nephrology

Background:

  • The oncological impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors remains incompletely understood.
  • SGLT2 inhibitors are widely prescribed for type 2 diabetes mellitus, chronic kidney disease, and heart failure.

Approach:

  • Systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials.
  • Searched PubMed and ClinicalTrials.gov databases up to July 15, 2023.
  • Analyzed overall and specific cancer incidences using Mantel-Haenszel method and fixed effects model.

Key Points:

  • SGLT2 inhibitors showed no significant increase in overall cancer incidence (RR 1.01; 95% CI 0.94-1.08).
  • Ertugliflozin significantly increased overall cancer incidence (RR 1.29; 95% CI 1.01-1.64).
  • Dapagliflozin significantly reduced bladder cancer risk (RR 0.53; 95% CI 0.35-0.81) and respiratory cancer risk (RR 0.74; 95% CI 0.55-1.00).
  • SGLT2 inhibitors were associated with an increased risk of renal cancer (RR 1.39; 95% CI 1.04-1.87).

Conclusions:

  • SGLT2 inhibitors do not elevate overall cancer risk or the risks of bladder and breast cancers.
  • The observed increased risk of renal cancer with SGLT2 inhibitors requires further investigation and clinical consideration.
  • Specific SGLT2 inhibitors demonstrate varied effects on cancer incidence, necessitating individualized treatment approaches.
Keywords:
Bladder cancerBreast cancerCancerDapagliflozinRenal cancerSodium-glucose cotransporter 2 inhibitor

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