Incretin-based Drugs and Acute Pancreatitis
Information source: Canadian Network for Observational Drug Effect Studies, CNODES
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus, Type 2
Intervention: DPP-4 inhibitors (Drug); GLP-1 analogs (Drug); Insulins (Drug); Biguanides (Drug); Sulfonylureas (Drug); Thiazolidinediones (Drug); Alpha-glucosidase inhibitors (Drug); Meglitinides (Drug)
Phase: N/A
Status: Completed
Sponsored by: Canadian Network for Observational Drug Effect Studies, CNODES Official(s) and/or principal investigator(s): Pierre Ernst, MD, MSc, Principal Investigator, Affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University
Summary
The purpose of this study is to determine whether incretin-based drugs (used to treat type 2
diabetes) taken either alone or in combination with other anti-diabetic drugs are associated
with an increased risk of acute pancreatitis (AP) compared to other combinations of oral
hypoglycemic agents (OHA).
The investigators will carry out separate population based cohort studies using
administrative health databases in six jurisdictions in Canada, the US, and the UK. Cohorts
will be defined by the initiation of a new anti-diabetic drug when incretin-based drugs
entered the market, with follow-up until hospitalization for AP. The results from the
separate sites will be combined to provide an overall assessment of the risk of AP in users
of incretin-based drugs and by class of incretin-based drugs.
Clinical Details
Official title: The Use of Incretin-based Drugs and the Risk of Acute Pancreatitis in Patients With Type 2 Diabetes
Study design: Observational Model: Cohort, Time Perspective: Retrospective
Primary outcome: Hospitalization for acute pancreatitis
Detailed description:
The study objective is to determine whether the use of incretin-based drugs, compared with
the use of oral anti-diabetic drug combinations, is associated with an increased risk of
acute pancreatitis (AP) in routine clinical practice. A common-protocol approach will be
used to conduct retrospective cohort studies using administrative health care data from six
jurisdictions (the Canadian provinces of Alberta, Manitoba, Ontario, and Saskatchewan, as
well as United States (US) MarketScan and the United Kingdom (UK) Clinical Practice Research
Datalink [CPRD]). Briefly, the Canadian databases include population-level data on physician
billing, diagnoses and procedures from hospital discharge abstracts, and dispensations for
prescription drugs. Ontario data will be restricted to patients aged 65 years and older as
prescription data are not available for younger patients. The CPRD is a clinical database
that is representative of the UK population and contains the records for patients seen at
over 680 general practitioner practices in the UK; these data will be linked to the Hospital
Episode Statistics (HES) database, which contains in-hospital diagnosis and procedure data.
US MarketScan includes individuals and their dependents covered by large U. S. employer
health insurance plans, and government and public organizations.
Study population
In each jurisdiction, the investigators will assemble a base cohort that includes all
patients with a first-ever prescription for a non-insulin anti-diabetic drug, including
biguanides, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 analogs,
alpha-glucosidase inhibitors, meglitinides or combinations of these drugs from the earliest
availability of data at each site to the last date of availability of data. The date of
prescription (for the CPRD) or dispensation (for all other sites) of the first-ever
non-insulin anti-diabetic drug will define the date of base cohort entry. From this base
cohort, a study cohort will be created including all patients who initiated a new
anti-diabetic drug class during the year in which incretin-based drugs entered the market in
each jurisdiction or any time thereafter. These new users consist of both those who are
newly-treated for diabetes, as well as those who switch to or add on a new anti-diabetic
drug class not included as part of their previous treatment history. The date of study
cohort entry is defined by the prescription date of the newly-prescribed drug class.
Patients in the study cohort will be followed from the date of study cohort entry until an
event (defined below) or censoring due to death, departure from the database, loss of
continuous health plan or drug plan enrolment, entry into a long-term care facility, an
incident diagnosis of HIV or new prescription of HAART, or the end of the study period (June
30, 2014 or the last date of data availability at that site), whichever occurs first.
Case-control selection
The cohort defined above will be analyzed using a nested case-control analysis, where cases
are defined as a hospitalization for AP. Risk set sampling will be used to randomly select
up to 20 controls for each case, matched on sex, age (± 365 days), date of study cohort
entry (± 180 days), duration of treated diabetes (± 90 days), and duration of follow-up in
days.
Exposure assessment
Current exposure to an anti-diabetic drug will be defined as any prescription whose duration
plus a 30-day grace period overlaps the index or event date. Current exposure will be
classified hierarchically based on the following five mutually-exclusive categories: 1)
incretin-based drugs; 2) insulin; 3) ≥2 oral anti-diabetic drugs used in combination
therapy; 4) oral anti-diabetic drug monotherapy; and 5) no current exposure to an
anti-diabetic drug. Oral anti-diabetic drugs used in combination will serve as the primary
reference category as incretin-based drugs are second- to third-line therapy and thus used
at a comparable point in the disease management.
Statistical analyses
Conditional logistic regression will be used to estimate odds ratios (ORs) and
corresponding 95% confidence intervals (CIs) of the association of hospitalization for AP,
comparing incretin-based drugs to current use of oral anti-diabetic drug combinations. This
is considered the primary analysis. Secondary analyses will include sub-classifying current
users of incretin-based drugs by type (i. e., DPP-4 inhibitor vs GLP-1 analog) and duration
of current use (≤ 365 days, 366-729 days, and ≥730 days). The potential presence of effect
modification by history of acute pancreatitis will also be examined. In addition, seven
sensitivity analyses will be conducted; all defined a priori, to assess the robustness of
the results. Finally, all site-specific estimates will be meta-analyzed using random-effects
models with inverse variance weighting, with fixed-effects analyses conducted as sensitivity
analyses. The amount of between-site heterogeneity will be estimated using the I square
statistic.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients with a first-ever prescription for a non-insulin anti-diabetic drug,
including biguanides, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1
analogs, alpha-glucosidase inhibitors, meglitinides or combinations of these drugs
from the earliest availability of data at each site to the last date of availability
of data.
- Patients with at least 1 year of history in the database.
- Patients at least 18 years of age.
Exclusion Criteria:
- Patients who died or left the cohort before the year the first incretin-based drug
entered the market.
- Patients who never added-on or switched to a new anti-diabetic drug after
incretin-based drugs entered the market up until June 30, 2014.
- Patients with a previous diagnosis of pancreatic cancer, those who underwent
pancreatectomy, those with diagnoses of congenital defects of the pancreas, cystic
fibrosis, lupus, or previous bariatric surgery, at any time prior to study cohort
entry.
- Patients diagnosed with HIV or initiating HAART therapy before and at study cohort
entry.
- Patients hospitalized for acute pancreatitis in the 30 days before study cohort
entry.
Locations and Contacts
Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T1E2, Canada
Additional Information
This organization's website describing general functions, other CNODES projects, and investigator profiles.
Starting date: March 2014
Last updated: June 17, 2015
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