Effect of Incretin Analogues and Dipeptidyl-peptidase-IV inhibitors on colorectal cancer risk

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10AE) Insulins and analogues for injection, long-acting

  Insulins and analogues for injection, long-acting

  (A10BB) Sulfonylureas

  Sulfonylureas

  (A10BG) Thiazolidinediones

  Thiazolidinediones

  (A10BH) Dipeptidyl peptidase 4 (DPP-4) inhibitors

  Dipeptidyl peptidase 4 (DPP-4) inhibitors
• Medical condition to be studied:
  Diabetes mellitus

Population studied

• Short description of the study population:
  66 years and older Medicare fee-for-service beneficiaries (20% random sample) who were enrolled in Medicare Part A, B, and D plans for at least one calendar month during 2007-2012 and initiating incretin-based drugs (GLP-1ra or DPP-4i) or other antidiabetic drugs (TZDs, sulfonylureas or long-acting insulins).
• Age groups:
  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  Diabetes mellitus patients
• Estimated number of subjects:
  175000

Study design details

• Main study objective:
  The primary objective of this study is to examine the effect of initiation of incretin-based therapies (DPP-4s and GLP-1s) relative to other anti-diabetic therapies (sulfonylureas, TZDs and long-acting insulins) on the incidence of colorectal cancer based on a new-user active comparator design.
• Outcomes:
  Incidence of colorectal cancer, Incidence of colorectal cancer or benign colorectal tumors, incidence of diagnostic work-up
• Data analysis plan:
  New-users of incretin-based therapies will be compared with new users of sulfonylureas, TZDs or long-acting insulins with respect to incidence of colorectal cancer diagnosis and the incidence of colorectal cancer or benign colorectal tumors. Using propensity score weighting methods, Inverse Probability of Treatment Weighting (IPTW) and Standardized MorbidityRatio Weighting (SMRW), we will implement COX models overall and stratified by time since initiation. Balance of the covariates will be assessed in the weighted pseudo-population and within deciles of the propensity score. Inverse probability weighted Kaplan-Meyer survival functions will be compared between our cohorts, adjusted for the same baseline covariates. The main effect measure estimate will be standardized hazard ratios with the assumptionthat there is no unmeasured confounding. Please see full protocol for additional details and description of secondary and sensitivity analyses.