To Assess the Risk of Acute Pancreatitis in Patients With Type 2 Diabetes Mellitus Treated With Empagliflozin

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 Drugs

To compare the risk of acute pancreatitis in patients with Type 2 diabetes mellitus (T2DM) newly initiating empagliflozin to that of patients newly initiating other oral non-incretin/non-Sodium glucose co-transporter-2 inhibitor (SGLT2i)-containing hypoglycemic agents.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: empagliflozin; Drug: Oral non-incretin/non-sodium glucose co-transporter-2 inhibitors (SGLT2)-containing hypoglycaemic agents

• Study Type: Observational
• Enrollment (Actual): 494679

Contacts and Locations

Study Locations

• Germany
  • Ingelheim am Rhein, Germany, 55216
    • Boehringer Ingelheim International GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients with a recorded diagnosis of Type 2 diabetes mellitus (T2DM) who initiated empagliflozin or other oral non-incretin/non-Sodium glucose co-transporter-2 inhibitor (SGLT2i)-containing hypoglycaemic agents (metformin, Sulfonylurea (SU), or Thiazolidinediones (TZD)) between 1 August 2014 and 31 October 2020 will be selected.

Description

Inclusion Criteria:

• Patients >= 18 years old
• A diagnosis of Type 2 diabetes mellitus (T2DM) as demonstrated by at least one qualifying diagnosis code from any encounter type recorded in the claims in the 6 months prior to the drug initiation.
• Patients initiating empagliflozin (as monotherapy, on a background of metformin, or on a background of metformin and Sulfonylurea (SU)) or qualifying comparator (metformin monotherapy, SU on a background of metformin, or Thiazolidinediones (TZD) on a background of metformin and SU) during the study period.
• 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 Sodium glucose co-transporter-2 inhibitor (SGLT2i), Dipeptidyl peptidase 4 inhibitors (DPP-4i) or Glucagon-like peptide-1 receptor agonist (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 us to remove severe cases of diabetes and reduce the risk of residual confounding as diabetes is a risk factor for developing acute pancreatitis.
• Patients with type 1 diabetes mellitus (T1DM) defined as at least 1 inpatient or outpatient International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code of 250.x1 or 250.x3 or International Classification of Diseases, Tenth Revision, Clinical Modification (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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pooled Empagliflozin; Patients with type 2 diabetes mellitus (T2DM) and new initiators of empagliflozin on a background of metformin, between 1-Aug-2014 and the latest data-cut available in IBM MarketScan Commercial Claims and Encounters (CCAE)/ Medicare Supplemental (MDCR) 30-Sep-2020 and Optum Clinformatics® Data Mart (CDM) 31-Mar-202, who were enrolled for a minimum of 6 months in the US claims databases before index treatment initiation	Drug: empagliflozin; empagliflozin
Pooled Sulfonylureas (SUs); Patients with type 2 diabetes mellitus (T2DM) and new initiators of Sulfonylureas (SUs) on a background of metformin, between 1-Aug-2014 and the latest data-cut available in IBM MarketScan Commercial Claims and Encounters (CCAE)/ Medicare Supplemental (MDCR) 30-Sep-2020 and Optum Clinformatics® Data Mart (CDM) 31-Mar-202, who were enrolled for a minimum of 6 months in the US claims databases before index treatment initiation	Drug: Oral non-incretin/non-sodium glucose co-transporter-2 inhibitors (SGLT2)-containing hypoglycaemic agents; Oral non-incretin/non-sodium glucose co-transporter-2 inhibitors (SGLT2)-containing hypoglycaemic agents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Acute Pancreatitis	Incidence rate of acute pancreatitis per number of person-years, defined as an acute pancreatitis diagnosis from any of the inpatient (not restricted to the primary diagnosis), outpatient, or emergency contacts diagnoses (ICD-9-CM 577.0 or ICD-10-CM K85) and a lipase measure within +/- 7 days of the acute pancreatitis diagnosis (using LOINC code of 3040-3 and 2572-6 or CPT code of 83690 for lipase) and an abdominal ultrasound (using CPT codes of 76700 and 76705) within +/- 7 days of the acute pancreatitis diagnosis. The incidence rate was reported as the number of events (counts the first event per patient) divided by the total number of person-years at risk during follow-up (1/(1000*person-years)).	From August 2014 to March 2021 (the study period). Up to 79 months.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2021
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): September 12, 2022

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pancreatic Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Pancreatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: 1245-0201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https:// www.mystudywindow.com/msw/datatransparency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No