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 identification

• EU PAS number:
  EUPAS30018
• Study ID:
  33386
• Official title and acronym:
  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)
• DARWIN EU® study:
  No
• Study countries:
  United States
• Study description:
  In August 2018, the US Food and Drug Administration (FDA) released a safety warning associating sodium-glucose cotransporter-2 inhibitors (SGLT2i), the newest class of antihyperglycemic drugs, with increased incidence of Fournier’s gangrene (FG), a rare, necrotizing fasciitis of the perineum. To validate this warning using real-world data, we propose to evaluate the association between SGLT2i initiation and FG risk using a large healthcare administrative claims database from the commercially-insured U.S. population (IBM Watson MarketScan Commercial Claims and Encounters). We will apply the active comparator, new user (ACNU) study design to estimate and compare the incidence of FG between patients who initiated SGLT2i and those who initiated comparable second-line glucose-lowering drugs (GLDs), dipeptidyl peptidase-4 inhibitors (DPP4i) and sulfonylureas (SU). Exposure to a study drug will be defined by at least two same-drug class prescription dispensing claims of either a SGLT2i or an active comparator drug. Fournier’s gangrene will be defined using combinations of ICD-9 and ICD-10 diagnosis codes, as well as ICD-9 procedure, ICD-10 procedure, Common Procedural (CPT), and National Drug Codes (NDCs) for systemic antibiotics, debridement, and related surgery.We will use propensity score methods to control for baseline confounding and estimate the average treatment effect in the treated. We will estimate the crude incidence rates of FG during follow-up for both the SGLT2i and comparator drug cohort, by dividing total number of observed cases during follow-up by the total person-time at risk. We will additionally estimate and compare the cumulative incidence of study outcomes for each study cohort using weighted Kaplan-Meier methods. Finally, crude and adjusted hazard ratios (HRs) for study outcomes will be estimated using weighted Cox proportional hazards models.
• Study status:
  Finalised

Research institutions and networks

Institutions

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill

Study timelines

Date when funding contract was signed

Planned:05/06/2019

Actual:05/06/2019

Study start date

Planned:05/06/2019

Actual:05/06/2019

Data analysis start date

Planned:05/06/2019

Actual:05/06/2019

Date of final study report

Planned:31/12/2019

Actual:15/01/2020

Sources of funding

No external funding

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable