Potential preventive properties of GLP-1 receptor agonists against prostate cancer: a nationwide cohort study

Diabetologia. 2023 Nov;66(11):2007-2016. doi: 10.1007/s00125-023-05972-x. Epub 2023 Aug 3.

Abstract

Aims/hypothesis: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to possess antineoplastic properties against prostate cancer. We examined the association between GLP-1RA use and prostate cancer risk in a real-world setting.

Methods: We performed a nationwide register-based cohort study using an active-comparator, new-user design. We included all men in Denmark aged ≥50 years who commenced use of GLP-1RAs or basal insulin during 2007-2019. HRs and 95% CIs for incident prostate cancer were estimated using multivariable Cox regression in 'intention-to-treat' (ITT)- and 'per-protocol'-like analyses.

Results: Among 14,206 initiators of GLP-1RAs and 21,756 initiators of basal insulin, we identified 697 patients with prostate cancer during a mean follow-up period of about 5 years from initiation of the study drugs. In comparison with basal insulin use, GLP-1RA use was associated with an adjusted HR of 0.91 (95% CI 0.73, 1.14) in the 'ITT' analysis and 0.80 (95% CI 0.64, 1.01) in the 'per-protocol' analysis. Stronger inverse associations were seen among older men (≥70 years) ('ITT' HR 0.56; 95% CI 0.38, 0.82; 'per-protocol' HR 0.47; 95% CI 0.30, 0.74), and in patients with CVD ('ITT' HR 0.75; 95% CI 0.53, 1.06; 'per-protocol' HR 0.60; 95% CI 0.39, 0.91).

Conclusions/interpretation: GLP-1RA use was inversely associated with prostate cancer risk compared with use of basal insulin in the 'per-protocol' analysis. Older men and patients with CVD exhibited stronger inverse associations in both the 'ITT' and 'per-protocol' analyses. Our results may indicate that GLP-1RA use could protect against prostate cancer.

Keywords: GLP-1 receptor agonist; Nationwide cohort study; Prostate cancer; Real-world evidence, Risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases* / complications
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulins*
  • Male
  • Prostatic Neoplasms* / complications
  • Prostatic Neoplasms* / prevention & control

Substances

  • Hypoglycemic Agents
  • Glucagon-Like Peptide-1 Receptor
  • Insulins