Post-authorization safety study (PASS) to assess the risk of acute pancreatitis in type 2 diabetes mellitus (T2DM) patients newly initiating empagliflozin compared to other oral non-incretin/non-sodium glucose co-transporter-2 inhibitors (SGLT2)-containing glucose lowering agents

Study type

• Study topic:
  Human medicinal product

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

  Disease epidemiology

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  Empagliflozin
• Medical condition to be studied:
  Diabetes mellitus

  Pancreatitis acute

Population studied

• Short description of the study population:
  The study population included type 2 diabetes mellitus (T2DM) patients aged 18 years or older, received treatment with empagliflozin or other oral non-incretin/non-SGLT2i-containing glucose lowering drugs (metformin, SU, or TZD) between 1 August 2014 to 31 March 2021 identified from the Truven Marketscan (CCAE and MDCR) database and Optum Clinformatics® Data Mart.; Inclusion criteria:; - Patients >= 18 years old; - A diagnosis of T2DM as demonstrated by at least one qualifying diagnosis code (International Classification of Diseases (ICD)-9-CM diagnosis code of 250.x0 or 250.x2; ICD-10-CM diagnosis code of E11.x) from any encounter type recorded in the claims in the 6 months prior to the drug initiation.; -Have at least 6 months of continuous registration in the database prior to initiation of empagliflozin or a comparator drug; ; Exclusion criteria:; - Patients with missing or ambiguous age or sex information.; - Use of a SGLT2i, DPP-4i or GLP-1 RA in the 6 months prior to study drug initiation.; - Chronic use of insulin in the outpatient setting in the 6 months prior to the study drug initiation. This criterion will help to remove severe cases of diabetes and reduce the risk of residual confounding as diabetes is a risk factor for developing acute pancreatitis [R10-6620, R10-2088]. ; - Patients with type 1 diabetes mellitus (T1DM) defined as at least 1 inpatient or outpatient ICD-9-CM diagnosis code of 250.x1 or 250.x3 or ICD-10-CM diagnosis code of E10.x in the 6 months prior to the study drug initiation.; - Patients with secondary diabetes or gestational diabetes in the 6 months prior to the study drug initiation.; - Claims for acute or chronic pancreatitis, pancreatic cancer, or other disease of the pancreas any time prior to the study drug initiation.
• 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:
  Patients with type 2 diabetes
• Estimated number of subjects:
  70000

Study design details

• Main study objective:
  The objective of the study is to compare the incidence rate of acute pancreatitis in T2DM patients initiating empagliflozin to new users of other oral non-incretin/non-SGLT2i-containing hypoglycaemic agents between 1 August 2014 and the latest data-cut available in Marketscan (30 September 2020) and Optum (31 March 2021).
• Outcomes:
  The objective of the study is to compare the incidence rate of acute pancreatitis in T2DM patients initiating empagliflozin to new users of other oral non-incretin/non-SGLT2i-containing hypoglycaemic agents between 1 August 2014 and the latest data-cut available in Marketscan (30 September 2020) and Optum (31 March 2021).
• Data analysis plan:
  The incidence rates (per 1000 PY) and corresponding 95% confidence intervals (CI) of acute pancreatitis during the follow-up time will be calculated in each exposure group of interest in the unmatched and propensity score (PS)-matched cohorts. Cox proportional hazards regression models based on time-to first acute pancreatitis event will be used to estimate hazard ratios (HR) and 95% CIs for each treatment line comparison of interest in the unmatched and PS-matched cohorts.