Incretin-based Drugs and Pancreatic Cancer

NCT02475499 | Completed

• 1 other identifier: Q13-06A
• Study Type: observational
• Target: 886,172
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether incretin-based drugs (used to treat type 2 diabetes) taken either alone in or combination with other anti-diabetic drugs are associated with an increased risk of pancreatic cancer (PC) compared to sulfonylureas. The investigators will carry out separate population based cohort studies using administrative health databases in five 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 PC. The results from the separate sites will be combined to provide an overall assessment of the risk of PC in users of incretin-based drugs and by class of incretin-based drugs.

Conditions

Diabetes Mellitus, Type 2

Keywords

Incretins; Antidiabetic agents; Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Incident pancreatic cancer

  Incident cases of pancreatic cancer recorded in a hospital database with the following ICD codes: ICD-9:157.0-157.9 ICD-10:C25.x

  Patients were followed from the date of study cohort entry until hospitalization for incident pancreatic cancer, censoring, or for up to 79 months.

Study Arms (3)

Treated with incretins

Ever-use of incretin-based drugs ((DPP-4 inhibitors \[sitagliptin, vildagliptin, and saxagliptin\] or GLP-1 analogs \[exenatide, liraglutide\]) between (and including) base cohort entry and the index day - 365 days.

Drug: DPP-4 inhibitors; Drug: GLP-1 analogs

Treated with sulfonylureas

Ever-use of sulfonylureas between (and including) base cohort entry and the index day - 365 days, and never-use of incretin-based drugs.

Drug: Sulfonylureas

Treated with other antidiabetic agents

Ever-use of other antidiabetic agents (biguanides, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides) between (and including) base cohort entry and the index day - 365 days, with never-use of incretin-based drugs and never use of sulfonylureas.

Drug: Biguanides; Drug: Thiazolidinediones; Drug: Alpha-glucosidase inhibitors; Drug: Meglitinides

Interventions

DPP-4 inhibitors DRUG

Ever-use of DPP-4 inhibitors (ATC A10BH, A10BD07-A10BD13) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: incretin-based drugs, sitagliptin, vildagliptin, saxagliptin

Treated with incretins

GLP-1 analogs DRUG

Ever-use of GLP-1 analogs (ATC A10BX04, A10BX07) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: incretin-based drugs, exenatide, liraglutide

Treated with incretins

Sulfonylureas DRUG

Ever-use of sulfonylureas (ATC A10BB or A10BC) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: oral hypoglycemic agent, glibenclamide, chlorpropamide, tolbutamide, glibornuride, tolazamide, carbutamide, glipizide, gliquidone, gliclazide, metahexamide, glisoxepide, glimepiride, acetohexamide, glymidine

Treated with sulfonylureas

Biguanides DRUG

Ever-use of biguanides (ATC A10BA) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: oral hypoglycemic agent, phenformin, metformin, buformin

Treated with other antidiabetic agents

Thiazolidinediones DRUG

Ever-use of thiazolidinediones (ATC A10BG) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: oral hypoglycemic agent, troglitazone, rosiglitazone, pioglitazone

Treated with other antidiabetic agents

Alpha-glucosidase inhibitors DRUG

Ever-use of alpha-glucosidase inhibitors (ATC A10BF) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: oral hypoglycemic agent, acarbose, miglitol, voglibose

Treated with other antidiabetic agents

Meglitinides DRUG

Ever-use of meglitinides (ATC A10BX02, A10BX03) will be defined as a prescription occurring between (and including) base cohort entry and the index day - 365 days.

Also known as: oral hypoglycemic agent, repaglinide, nateglinide

Treated with other antidiabetic agents

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In each jurisdiction, a base cohort will be assembled including all patients with a first-ever prescription for a non-insulin anti-diabetic drug. Base cohort entry is defined as the date of prescription or dispensation of the first-ever non-insulin anti-diabetic drug. From this base cohort, a study cohort will be formed consisting of 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. Study cohort entry is defined by the prescription date of the newly-prescribed drug class.

You may qualify if:

• 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.

You may not qualify if:

• 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 or were diagnosed with congenital defects of the pancreas at any time prior to study cohort entry.
• Patients with less than 365 days of follow-up after study cohort entry

Sponsors & Collaborators

• Canadian Network for Observational Drug Effect Studies, CNODES: lead
• Drug Safety and Effectiveness Network, Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Lady Davis Institute for Medical Research, Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Related Publications (1)

• Azoulay L, Filion KB, Platt RW, Dahl M, Dormuth CR, Clemens KK, Durand M, Juurlink DN, Targownik LE, Turin TC, Paterson JM, Ernst P; Canadian Network for Observational Drug Effect Studies Investigators. Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. BMJ. 2016 Feb 17;352:i581. doi: 10.1136/bmj.i581.

  PMID: 26888382 RESULT

Related Links

• This organization's website describing general functions, other CNODES projects, and investigator profiles.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Pancreatic Neoplasms

Interventions

Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Vildagliptin; saxagliptin; Glucagon-Like Peptide-1 Receptor Agonists; Exenatide; Liraglutide; Sulfonylurea Compounds; Hypoglycemic Agents; Glyburide; Chlorpropamide; Tolbutamide; glibornuride; Tolazamide; Carbutamide; Glipizide; gliquidone; Gliclazide; metahexamide; glisoxepide; glimepiride; Acetohexamide; glymidine; Biguanides; Phenformin; Metformin; Buformin; Thiazolidinediones; Troglitazone; Rosiglitazone; Pioglitazone; Glycoside Hydrolase Inhibitors; Acarbose; miglitol; voglibose; meglitinide; repaglinide; Nateglinide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Nitriles; Organic Chemicals; Pyrrolidines; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Urea; Amides; Sulfones; Sulfur Compounds; Benzenesulfonamides; Sulfonamides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Guanidines; Amidines; Thiazoles; Chromans; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Trisaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Pierre Ernst, MD, MSc

  Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 18, 2015
• Study Start: March 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: March 14, 2016

Record last verified: 2016-03

Locations

CA (1)