Incretin-based Drugs and the Risk of Heart Failure
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| ClinicalTrials.gov Identifier: NCT02456428 |
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Recruitment Status :
Completed
First Posted : May 28, 2015
Last Update Posted : April 19, 2016
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Sponsor:
Canadian Network for Observational Drug Effect Studies, CNODES
Collaborators:
Drug Safety and Effectiveness Network, Canada
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Canadian Network for Observational Drug Effect Studies, CNODES
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Brief 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 heart failure (HF) 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 HF. Analyses will be done separately for groups of patients with and without prior HF. The results from the separate sites will be combined to provide an overall assessment of the risk of HF in users of incretin-based drugs and by class of incretin-based drugs.
| Condition or disease | Intervention/treatment |
|---|---|
| Type 2 Diabetes Mellitus | Drug: DPP-4 inhibitors Drug: GLP-1 analogs Drug: Insulins Drug: Biguanides Drug: Sulfonylureas Drug: Thiazolidinediones Drug: Alpha-glucosidase inhibitors Drug: Meglitinides |
Show Detailed Description
| Study Type : | Observational |
| Actual Enrollment : | 1499650 participants |
| Observational Model: | Cohort |
| Time Perspective: | Retrospective |
| Official Title: | Incretin-based Drugs and the Risk of Heart Failure: A Multi-center Network Observational Study |
| Study Start Date : | March 2014 |
| Actual Primary Completion Date : | May 2015 |
| Actual Study Completion Date : | May 2015 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Type 2 diabetes
MedlinePlus related topics:
Heart Failure
| Group/Cohort | Intervention/treatment |
|---|---|
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Treated with incretins
Current use of incretin-based drugs ((DPP-4 inhibitors [sitagliptin, vildagliptin, and saxagliptin] or GLP-1 analogs [exenatide, liraglutide]) alone or in combination with other anti-diabetic drugs (if the prescription overlaps with the index or event day with a 30-day grace period).
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Drug: DPP-4 inhibitors
Current exposure to DPP-4 inhibitors (ATC A10BH, A10BD07-A10BD13) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: GLP-1 analogs Current exposure to GLP-1 analogs (ATC A10BX04, A10BX07) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
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Treated with insulin
Current use of insulins between base cohort entry and the index or event day (alone or in combination with other anti-diabetic drugs) and no current use of incretin-based drugs.
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Drug: Insulins
Current exposure to insulin (ATC A10A) will be defined as any use of insulin between base cohort entry and the index day.
Other Names:
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Treated with ≥2 oral hypoglycemic agents
Current use of 2 or more non-insulin anti-diabetic medications (biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides) (if the prescriptions overlap with the index or event day with a 30-day grace period), and no current use of incretin-based drugs or insulins.
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Drug: Biguanides
Current exposure to biguanides (ATC A10BA) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Sulfonylureas Current exposure to sulfonylureas (ATC A10BB or A10BC) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Thiazolidinediones Current exposure to thiazolidinediones (ATC A10BG) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Alpha-glucosidase inhibitors Current exposure to alpha-glucosidase inhibitors (ATC A10BF) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Meglitinides Current exposure to meglitinides (ATC A10BX02, A10BX03) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index (event)day.
Other Names:
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Treated with single oral agent
Current use of any single non-insulin anti-diabetic medications (biguanides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides) (if the prescription overlaps with the index or event day with a 30-day grace period) and no current use of more than 2 OHAs, incretin-based drugs, or insulins.
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Drug: Biguanides
Current exposure to biguanides (ATC A10BA) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Sulfonylureas Current exposure to sulfonylureas (ATC A10BB or A10BC) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Thiazolidinediones Current exposure to thiazolidinediones (ATC A10BG) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Alpha-glucosidase inhibitors Current exposure to alpha-glucosidase inhibitors (ATC A10BF) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index day.
Other Names:
Drug: Meglitinides Current exposure to meglitinides (ATC A10BX02, A10BX03) will be defined as a prescription duration plus a 30-day grace period (to account for non-adherence and the biological half-lives of these drugs) that overlaps with the index (event)day.
Other Names:
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Not currently exposed group
All patients not currently exposed to: incretin-based drugs, insulins, ≥2 OHAs, or a single OHA.
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Primary Outcome Measures :
- Hospitalization for incident heart failure [ Time Frame: Patients were followed from the date of study cohort entry until hospitalization for incident heart failure, censoring, or for up to 87 months. ]
Patients hospitalized for incident heart failure (HF) recorded in either the discharge abstract or hospitalization record with the following ICD codes:
ICD-9 code: 428.x
ICD-10 code: I50.x
For patients who had no history of prior HF, cases were identified by the presence of a HF diagnosis in any position (most responsible, primary, or secondary), while for patients with a history of established HF, the event definition was restricted to those with a HF diagnosis as the primary or most responsible reason for hospitalization.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| 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 a 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. Two separate cohorts will be created based on the presence or absence of a history of HF prior to and including study cohort entry.
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 diagnosed with HIV or initiating HAART therapy before and at study cohort entry.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02456428
Locations
| Canada, Quebec | |
| Lady Davis Institute for Medical Research, Jewish General Hospital | |
| Montreal, Quebec, Canada, H3T1E2 | |
Sponsors and Collaborators
Canadian Network for Observational Drug Effect Studies, CNODES
Drug Safety and Effectiveness Network, Canada
Canadian Institutes of Health Research (CIHR)
Investigators
| Principal Investigator: | Pierre Ernst, MD, MSc | Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University |
Publications of Results:
| Responsible Party: | Canadian Network for Observational Drug Effect Studies, CNODES |
| ClinicalTrials.gov Identifier: | NCT02456428 History of Changes |
| Other Study ID Numbers: |
Q13-06C |
| First Posted: | May 28, 2015 Key Record Dates |
| Last Update Posted: | April 19, 2016 |
| Last Verified: | April 2016 |
Keywords provided by Canadian Network for Observational Drug Effect Studies, CNODES:
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Incretins Antidiabetic Agents Heart Failure |
Additional relevant MeSH terms:
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Diabetes Mellitus Heart Failure Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Heart Diseases Cardiovascular Diseases Insulin Insulin, Globin Zinc Sitagliptin Phosphate Pioglitazone Liraglutide Exenatide Saxagliptin |
Rosiglitazone Vildagliptin 2,4-thiazolidinedione Biguanides Meglitinide Troglitazone Acetohexamide Hypoglycemic Agents Incretins Dipeptidyl-Peptidase IV Inhibitors Glycoside Hydrolase Inhibitors Physiological Effects of Drugs Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Protease Inhibitors |