SGLT2 Inhibitors and the Risk of Hospitalization for Fournier’s Gangrene: a Nested Case-control Study (MK-8835-067)

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:
  Case-control

  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10BK) Sodium-glucose co-transporter 2 (SGLT2) inhibitors

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

Population studied

• Short description of the study population:
  The cohort will include patients ≥18 years who are prescribed at least one antihyperglycemic agent between April 1, 2013 (when the first SGLT2 inhibitor was available in the US) and March 31, 2018 (latest available data). ; ; We will identify all patients who were prescribed at least one AHA agent between April 1, 2013 and March 31, 2018 and had at least 1 claim of type 2 diabetes diagnosis during the study period. Cohort entry date will be defined as the date of the first prescription claim for an AHA during the study period. The AHAs considered at cohort entry will consist of metformin, sulfonylureas (SU), thiazolidinediones (TZD), acarbose, meglitinides, a prandial glucose regulator, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, SGLT-2 inhibitors and insulin. We will restrict our cohort to patients aged at least 18 years of age at the time of their cohort entry and who are continuously enrolled in the health plan for ≥ 6 months before the study cohort entry. We will exclude patients who had previously received a diagnosis of human immunodeficiency virus (HIV) infection, or patients who had a previous diagnosis of Fournier’s gangrene before study cohort entry. Patients with a principal diagnosis of type 1 diabetes, women with a diagnosis of gestational diabetes and those with a principal diagnosis of polycystic ovary syndrome (for whom metformin can be prescribed) will also be excluded.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • 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:
  Type 2 diabetes mellitus patients
• Estimated number of subjects:
  600

Study design details

• Main study objective:
  The primary objective is to assess whether the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors was associated with an increased risk of hospitalization for Fournier’s gangrene as compared with other non-SGLT2- inhibitor antihyperglycemic agents (AHAs).
• Outcomes:
  The study's primary outcome will be hospitalization for Fournier’s gangrene.
• Data analysis plan:
  Descriptive statistics will be used to summarize the characteristics of the cases and matched controls. A nested case-control analysis will then be performed to investigate the association between the use of SGLT2 inhibitors and the incidence of Fournier's gangrene hospitalization. Conditional logistic regression will be used to estimate odds ratios and corresponding 95% confidence intervals for the association between SGLT2 inhibitors and the risk of Fournier's gangrene, with the use of risk set sampling, these odds ratios are unbiased estimators of the hazard ratio.