Incidence of Diabetic Ketoacidosis among Patients with Type 2 Diabetes Mellitus Treated with SGLT2 inhibitors or Other Antihyperglycemic Agents- A Retrospective, Observational, New-User Cohort Study Using an Administrative Claims Database in the US

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

  Other
• If ‘other’, further details on the scope of the study:
  Primary scope: Comparison of adverse event risk between user of index drugs and comparator drugs.
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  INVOKANA

  VOKANAMET
• Study drug International non-proprietary name (INN) or common name:
  CANAGLIFLOZIN

  DAPAGLIFLOZIN

  METFORMIN
• 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:
  Diabetic ketoacidosis

Population studied

• Short description of the study population:
  Patients with Type 2 Diabetes Mellitus treated with SGLT2 inhibitors or other antihyperglycemic agents.
• 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)
• Special population of interest:
  Other
• Special population of interest, other:
  Diabetes mellitus patients
• Estimated number of subjects:
  60392

Study design details

• Main study objective:
  To compare the incidence of diabetic ketoacidosis (DKA) among patients diagnosed with type 2 diabetes and pair-matched on exposure propensity scores (EPS) for new use of any SGLT2 inhibitor class versus new use of various other antihyperglycemic agents (AHAs), combined as one group.
• Outcomes:
  First incident diabetic ketoacidosis diagnosis recorded in hospital or emergency room over the study period.
• Data analysis plan:
  Baseline characteristics are summarized for patients treated with SGLT2i versus other AHAs. Between-group differences are assessed using Wilcoxon rank-sum tests for continuous variables and chi-squared tests for categorical variables. The standardized difference after propensity-score matching are also presented. Large scale exposure propensity score is estimated using regularized logistic regression models.The crude incidence rates of DKA in each AHA new-user cohorts are estimated as the number of first incident DKA cases divided by the total at-risk follow-up time, reported as number of cases per 1,000 person-years at risk. We use a conditional Cox proportional hazards model to estimate hazard ratio associated with SGLT2i versus other AHAs. Each propensity-score matched set is treated as a separate stratum in Cox model. P-values <0.05 is considered statistically significant, all stat. tests are two-sided. Empirical p-value calibration is conducted to address potential systemic bias