Sodium-Glucose Cotransporter-2 Inhibitor (SGLT-2i) Use and Risk of Subsequent Amputation

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10BB) Sulfonylureas

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

  (A10BK) Sodium-glucose co-transporter 2 (SGLT2) inhibitors
• Medical condition to be studied:
  Diabetes mellitus management

  Debridement

  Diabetic foot

  Peripheral vascular disorder

  Peripheral revascularisation
• Additional medical condition(s):
  Lower-extremity amputation

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  300000

Study design details

• Main study objective:
  To evaluate and compare the association between SGLT-2 inhibitor initiation, relative to other second-line glucose lowering drugs DPP-4 inhibitors and sulfonylureas, on the incidence and risk of diabetes-related amputation, based on a new-user, active comparator study design.
• Outcomes:
  The primary outcome of interest is lower extremity amputation (LEA), defined using ICD-9 or CPT procedure codes. In secondary outcome analysis, we will assess the association between SGLT-2i initiation and other consequences of diabetic disease, including the following conditions: debridement, diabetic foot ulcer and gangrene, peripheral vascular disease (PVD), and peripheral revascularization. These conditions will be identified using ICD-9 diagnosis and procedure codes as well as CPT procedure codes.
• 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 and compare the cumulative incidence of both primary and secondary outcomes 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.

Documents

Study publications

Yang JY, Wang T, Pate V, Gower EW, Crowley MJ, Buse JB, Stürmer T. Sodium-Gluco…