Clinical trial NCT05663515: A Pan-European Post-Authorisation Safety Study: Risk of Pancreatic Cancer Among Type 2 Diabetes Patients Who Initiated Exenatide as Compared With Those Who Initiated Other Non-Glucagon-Like Peptide 1 Receptor Agonists Based Glucose Lowering Drugs
Official title: EXCEED - A Pan-European Post-Authorisation Safety Study: Risk of Pancreatic Cancer Among Type 2 Diabetes Patients Who Initiated Exenatide as Compared With Those Who Initiated Other Non-Glucagon-Like Peptide 1 Receptor Agonists Based Glucose Lowering Drugs
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreatic Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Pvt. Ltd
First posted: 2022-12-23
Enrollment: 24000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with T2DM, aged 18 years or older, who initiated treatment with exenatide or non-GLP-1 RA based GLDs during the study period, 2006 to 2023, will be included. Exposure to exenatide and non-GLP-1 RA based GLDs will be ascertained from recordings of prescriptions or insurance claims registrations as available in the different data sources.

Brief summary: EXCEED is a non-interventional post-authorisation safety study aiming to assess the risk of developing pancreatic cancer among type 2 diabetes mellitus (T2DM) patients who initiated exenatide compared to those who initiated other non-glucagon like peptide 1 receptor agonists (GLP-1 RA) based glucose lowering drugs (GLDs). Study data will be collected from secondary data sources across 7 European countries. The study will be conducted as a multi-country, long-term, retrospective, observational database study. Initiators of exenatide will be matched to initiators of non-GLP-1 RA based GLDs (comparator group) based on propensity score and calendar period of study entry. All analyses for pancreatic cancer will be conducted in the matched study population using an "intention-to-treat" approach. The study will use information from 8 data sources in 7 European countries (France, Spain, The United Kingdom, Finland, Denmark, Norway, and Sweden). Patients with T2DM, aged 18 years or older, who initiated treatment with exenatide or non-GLP-1 RA based GLDs during the study period, 2006 to 2023, will be included. Exposure to exenatide and non-GLP-1 RA based GLDs will be ascertained from recordings of prescriptions or insurance claims registrations as available in the different data sources. The outcome of pancreatic cancer will be defined as a primary diagnosis of pancreatic cancer during follow-up


Eligibility criteria: For inclusion in either exposure group, all of the following inclusion criteria must be fulfilled:

1. Aged 18 years or older at the index date
2. Individual level data on prescriptions, diagnoses and medical history is available for a minimum of 12 months prior to the index date
3. A diagnosis of T2DM on index date or prior to index date

For inclusion in the overall exenatide exposure group, the following criterion must be fulfilled:

1. One incident prescription (or incident dispensed prescription) for exenatide (BYETTA or BYDUREON/ BYDUREON BCise) between the start and 12 months before the end of the study period. This incident prescription must have succeeded a prescription of a GLD of another drug class during the baseline period.

   For inclusion in the BYDUREON/ BYDUREON BCise exposure group, for the analyses of the secondary objective, the criterion a) is substituted with criterion b):
2. One incident prescription (or incident dispensed prescription) for BYDUREON/ BYDUREON BCise between the start and 12 months before the end of the study period. This incident prescription must have succeeded a prescription of a GLD of another drug class during the baseline period.

   For inclusion in the comparator group, the following criterion must be fulfilled:
3. One incident prescription (or incident dispensed prescription) of a GLD between the start and 12 months before the end of the study period. The GLD must not be a DPP-4i, a GLP-1 RA, or a combination with either a DPP-4i or a GLP-1 RA. This incident prescription must have succeeded a prescription of a GLD of another drug class during the baseline period.

Patients are not eligible for any of the study population groups if they fulfil any of the following exclusion criteria:

1. A diagnosis of type 1 diabetes mellitus (T1DM) on index date or a diagnosis of T1DM during the baseline period that is not succeeded by a T2DM diagnosis during the remaining part of the baseline period.
2. A diagnosis of gestational diabetes during the baseline period or on index date.
3. A diagnosis of polycystic ovarian syndrome during the baseline period or on index date in combination with exposure to metformin (Anatomical Therapeutic Chemical Classification System (ATC) code of the World Health Organization (WHO): A10BA02) as the only GLD on index date or during the baseline period.
4. History of any cancer on or prior to index date. The only exception is that nonmelanoma skin cancer does not lead to exclusion.
5. History of any acute pancreatitis, other diseases of the pancreas, or disorders of the pancreas on or prior to index date.
6. One or more prescriptions (or dispensed prescriptions) of a GLP-1 RA (incretin mimetics) other than exenatide on or prior to index date.
7. One or more prescriptions (or dispensed prescriptions) of DPP-4i (incretin mimetics) on or prior to the index date.

Primary outcomes:
measure: Incidence rate of primary diagnosis of pancreatic cancer among exenatide exposed population
timeFrame: Follow-up starts from the index date to the study completion, an average of 1.5 years or less
measure: Hazard ratio of primary diagnosis of pancreatic cancer among exenatide exposed population
timeFrame: Follow-up starts from thr index date to the study completion, an average of 1.5 years or less
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Bergen
country: Norway
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Vänersborg
country: Sweden
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Iqvia Pty Ltd
name: Fabian Hoti, PhD
role: PRINCIPAL_INVESTIGATOR
References: