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

NCT05663515 | Recruiting FDA Drug

• 1 other identifier: D5551R00015
• Study Type: observational
• Target: 24,000
• Locations: 7 countries
• Sites: 8

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence rate of primary diagnosis of pancreatic cancer among exenatide exposed population

  To estimate the incidence rate (IR) for pancreatic cancer associated with exposure to exenatide, compared with exposure to non-GLP-1 RA based GLDs, among patients with T2DM.

  Follow-up starts from the index date to the study completion, an average of 1.5 years or less

• Hazard ratio of primary diagnosis of pancreatic cancer among exenatide exposed population

  To estimate the hazard ratio (HR) for pancreatic cancer associated with exposure to exenatide, compared with exposure to non-GLP-1 RA based GLDs, among patients with T2DM.

  Follow-up starts from thr index date to the study completion, an average of 1.5 years or less

Study Arms (2)

Initiators of exenatide

Patients with T2DM, aged 18 years or older, who initiated treatment with exenatide during the study period, 2006 to 2023

Drug: Exenatide

Initiators of non-GLP-1 RA based glucose lowering drugs

Patients with T2DM, aged 18 years or older, who initiated treatment with non-GLP-1 RA based glucose lowering drugs during the study period, 2006 to 2023

Drug: Non-GLP-1 RA based glucose lowering drugs

Interventions

Exenatide DRUG

All patients initiating exenatide during the study period will be identified by ATC codes and be included in the exenatide group in a hierarchical manner, regardless of previous use of non-GLP-1 RA based glucose lowering drugs.

Also known as: BYETTA, BYDUREON/BYDUREON BCise

Initiators of exenatide

Non-GLP-1 RA based glucose lowering drugs DRUG

Initiators of non-GLP-1 RA based GLDs with no use of exenatide before or during the study period.

Also known as: Insulin/analogues (excl. A10AE54, A10A56), Biguanide, Sulfonylurea, Sulfonamide (heterocycl.), combined oral GLD (excl. DPP-4i), Alpha glucose inhib., Thiazolidinedione, SGLT2i, Oth. GLD excl. insulin

Initiators of non-GLP-1 RA based glucose lowering drugs

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.
• A diagnosis of gestational diabetes during the baseline period or on index date.
• 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.
• History of any acute pancreatitis, other diseases of the pancreas, or disorders of the pancreas on or prior to index date.
• One or more prescriptions (or dispensed prescriptions) of a GLP-1 RA (incretin mimetics) other than exenatide on or prior to index date.
• One or more prescriptions (or dispensed prescriptions) of DPP-4i (incretin mimetics) on or prior to the index date.

Sponsors & Collaborators

• AstraZeneca: lead
• IQVIA Pvt. Ltd: collaborator

Study Sites (8)

Research Site

Copenhagen, Denmark

RECRUITING

Research Site

Helsinki, Finland

RECRUITING

Research Site

Paris, France

RECRUITING

Research Site

Bergen, Norway

RECRUITING

Research Site

Barcelona, Spain

RECRUITING

Research Site

Vänersborg, Sweden

RECRUITING

Research Site

Edinburgh, United Kingdom

RECRUITING

Research Site

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Exenatide; Insulin; Biguanides; Sulfonylurea Compounds; Sulfonamides; 2,4-thiazolidinedione

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds

Study Officials

• Fabian Hoti, PhD

  IQVIA Pty Ltd

  PRINCIPAL INVESTIGATOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: December 23, 2022
• Study Start: September 30, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

FR (1); SE (1); GB (2); DK (1); ES (1); NO (1); FI (1)