Diabetes Mellitus, Type 2
Conditions
Brief summary
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.
Interventions
DRUGempagliflozin
empagliflozin
DRUGOral 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
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Acute Pancreatitis | From August 2014 to March 2021 (the study period). Up to 79 months. | 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)). |
Countries
Germany
Participant flow
Recruitment details
A Post-authorization safety study based on existing data between 1-Aug-2014 and the latest data-cut available in IBM MarketScan (30-Sep-2020) and Optum Clinformatics® Data Mart (CDM) 31-Mar-2021. The study aimed to assess the risk of acute pancreatitis in type 2 diabetes mellitus (T2DM) patients newly initiated in empagliflozin to that of newly initiated in other oral non incretin/non-sodium glucose co-transporter-2 inhibitors (SGLT2i)-based glucose lowering drugs. More details in Limitations.
Pre-assignment details
Every patient who fulfilled inclusion and exclusion criteria was selected until the required sample size was achieved.
Participants by arm
| Arm | Count |
|---|---|
| Pooled Empagliflozin - PS Matched 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-2021, who were enrolled for a minimum of 6 months in the US claims databases before index treatment initiation and matched on propensity scores. | 72,621 |
| Pooled Sulfonylureas (SUs) - PS Matched 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-2021, who were enrolled for a minimum of 6 months in the US claims databases before index treatment initiation and matched on propensity scores | 72,621 |
| Total | 145,242 |
Baseline characteristics
| Characteristic | Pooled Empagliflozin - PS Matched | Pooled Sulfonylureas (SUs) - PS Matched | Total |
|---|---|---|---|
| Age, Continuous | 56.67 Years STANDARD_DEVIATION 11.53 | 56.77 Years STANDARD_DEVIATION 11.73 | 56.7 Years STANDARD_DEVIATION 12 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 30253 Participants | 30442 Participants | 60695 Participants |
| Sex: Female, Male Male | 42368 Participants | 42179 Participants | 84547 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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)).
Time frame: From August 2014 to March 2021 (the study period). Up to 79 months.
Population: Pooled unmatched and 1:1 propensity scores (PS) matched cohort of patients with type 2 diabetes mellitus (T2DM) and new initiators of empagliflozin or sulfonylureas (SUs), who were enrolled between 1 August 2014 and the latest data-cut available in IBM MarketScan CCAE/MDCR (30 September 2020) and Optum CDM (31 March 2021). Primary analysis represented an 'as treated' approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled Empagliflozin - PS Matched | Incidence Rate of Acute Pancreatitis | 10.30 Events per 1,000 person-years |
| Pooled Sulfonylureas (SUs) - PS Matched | Incidence Rate of Acute Pancreatitis | 11.65 Events per 1,000 person-years |
95% CI: [0.76, 1.02]Regression, Cox