Sodium-Glucose Cotransporter-2 Inhibitor Use and Risk of Fournier’s Gangrene: Validating the US Food and Drug Administration Drug Warning (SGLT2i Use and FG 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:
  (A10BB) Sulfonylureas

  Sulfonylureas

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

  Dipeptidyl peptidase 4 (DPP-4) inhibitors

  (A10BK) Sodium-glucose co-transporter 2 (SGLT2) inhibitors

  Sodium-glucose co-transporter 2 (SGLT2) inhibitors
• Medical condition to be studied:
  Scrotal gangrene

  Diabetic gangrene

Population studied

• Short description of the study population:
  All MarketScan CCAE beneficiaries with at least one prescription dispensing claim for a SGLT2i or an active comparator drug between April 1, 2013 and June 30, 2017.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Diabetes mellitus patients
• Estimated number of subjects:
  300000

Study design details

• Main study objective:
  To evaluate and compare the association between SGLT2i initiation, relative to other second-line glucose lowering drugs (GLDs), on the incidence and risk of Fournier’s gangrene, based on an active comparator, new-user (ACNU) study design.
• Outcomes:
  Fournier’s gangrene will be defined using combinations of ICD-9 and ICD-10 diagnosis codes, and ICD-9 procedure, ICD-10 procedure, Common Procedure Terminology (CPT) and National Drug Codes (NDCs) for systemic antibiotics, debridement, and related surgery.
• Data analysis plan:
  We will use an active comparator, new user study design, which tends to synchronize patients with respect to diabetes severity and duration, to compare new users of SGLT-2i with new users of DPP-4i and sulfonylureas. We will use propensity scores to remove imbalances in measured potential confounders between study cohorts. We will estimate the crude incidence rates of FG during follow-up for both the SGLT2i and comparator drug cohort. We will additionally estimate and compare the cumulative incidence of FG for each study cohort using weighted Kaplan-Meier methods. Crude and adjusted hazard ratios (HRs) for both primary and secondary outcomes will be estimated using weighted Cox proportional hazards models, controlling for age, sex, as well as any potential confounders that remain unbalanced after propensity score implementation.