The impact of oral hypoglycemics and statins on outcomes in myelodysplastic syndromes

Ann Hematol. 2022 May;101(5):1023-1030. doi: 10.1007/s00277-022-04802-1. Epub 2022 Feb 22.

Abstract

Observational studies suggest an anti-neoplastic effect associated with statins, metformin, and dipeptidyl peptidase-4 inhibitors (DPP4i), while sulfonylureas may have a neutral or detrimental effect. We linked the Ontario subset of a prospective Canadian myelodysplastic syndromes (MDS) registry with provincial administrative databases. We assessed the impact of statin/oral hypoglycemic medication exposure on overall survival (OS) using Cox regression analysis, controlling for comorbidities and sociodemographic factors. Five hundred thirty-three patients aged ≥ 66 years were included: 49.3% used statins, 18.9% used metformin, 9.0% used sulfonylureas, and 6.4% used DPP4i. Three hundred ninety-five patients were lower-risk based on the International Prognostic Scoring System. On univariate analysis, we identified a marginal improvement in OS in the lower-risk group using DPP4i (HR 0.98, 95% CI 0.95-1.00, P = 0.05), while there was no impact on mortality for higher-risk DPP4i users (HR 1.03, CI 0.99-1.07, P = 0.21). There was no mortality difference for statins (HR 1.00, CI 1.00-1.01, P = 0.93), metformin (HR 1.00, CI 0.99-1.01, P = 0.81), or sulfonylureas (HR 1.00, CI 0.99-1.02, P = 0.43) in the entire cohort, as well as when stratified into lower/higher-risk groups. On multivariable analysis in the lower-risk group, there was no association between DPP4i and OS (HR 0.98, CI 0.95-1.00, P = 0.06). Prospective studies with larger cohorts of patients and longer follow-up are required to further study the impact of DPP4i in MDS.

Keywords: Dipeptidyl peptidase-4 inhibitor; Metformin; Myelodysplastic syndrome; Statin; Sulfonylurea.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hypoglycemic Agents / therapeutic use
  • Metformin* / therapeutic use
  • Myelodysplastic Syndromes* / complications
  • Myelodysplastic Syndromes* / drug therapy
  • Ontario
  • Prospective Studies
  • Retrospective Studies
  • Sulfonylurea Compounds / therapeutic use
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Metformin