Type 2 Diabetes MellitusNCT02456428
Incretin-based Drugs and the Risk of Heart Failure
An observational study of Type 2 Diabetes Mellitus, run by Canadian Network for Observational Drug Effect Studies, CNODES at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- DPP-4 inhibitors, GLP-1 analogs and Insulins
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 1,499,650 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2014to May 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Lady Davis Institute for Medical Research, Jewish General Hospital
Montreal, Quebec, H3T1E2
About this study
Official title: Incretin-based Drugs and the Risk of Heart Failure: A Multi-center Network Observational Study
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.
Read the 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 heart failure (HF) in routine clinical practice. The investigators will use a common-protocol approach 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 the 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.
For the purpose of this study, two separate cohorts will be created based on the presence or absence of a history of HF at any time prior to and including the date of study cohort entry. Patients in each 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 cohorts defined above will be analyzed using a nested case-control analysis, where cases are defined as a hospitalization for HF. 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 with 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
All analyses will be conducted separately among patients with and without a history of HF. Conditional logistic regression will be used to estimate the odds ratios and corresponding 95% confidence intervals (CIs) of the association of hospitalization for HF, comparing current use of incretin-based drugs to 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 a history of myocardial infarction (MI) will also be explored. 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 in the sensitivity analyses. The amount of between-site heterogeneity will be estimated using the I square statistic.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- DPP-4 inhibitors, GLP-1 analogs, Insulins, Biguanides, Sulfonylureas
- Keywords
- Incretins, Antidiabetic Agents, Heart Failure
- Medical subject headings
- Diabetes Mellitus, Type 2, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DPP-4 inhibitorsDrug
Also called incretin-based drugs, sitagliptin, vildagliptin, saxagliptin
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.
GLP-1 analogsDrug
Also called incretin-based drugs, exenatide, liraglutide
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.
InsulinsDrug
Also called insulins and analogues for injection, fast-acting, insulins and analogues for injection, intermediate-acting, insulins and analogues for injection, long-acting, insulins and analogues for inhalation
Current exposure to insulin (ATC A10A) will be defined as any use of insulin between base cohort entry and the index day.
BiguanidesDrug
Also called oral hypoglycemic agent, phenformin, metformin, buformin
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.
SulfonylureasDrug
Also called oral hypoglycemic agent, glibenclamide, chlorpropamide, tolbutamide
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.
ThiazolidinedionesDrug
Also called oral hypoglycemic agent, troglitazone, rosiglitazone, pioglitazone
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.
Alpha-glucosidase inhibitorsDrug
Also called oral hypoglycemic agent, acarbose, miglitol, voglibose
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.
MeglitinidesDrug
Also called oral hypoglycemic agent, repaglinide, nateglinide
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: DPP-4 inhibitors; Drug: GLP-1 analogs | |
| 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. Receives: Drug: Insulins | |
| 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. Receives: Drug: Biguanides; Drug: Sulfonylureas; Drug: Thiazolidinediones; Drug: Alpha-glucosidase inhibitors; Drug: Meglitinides | |
| 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. Receives: Drug: Biguanides; Drug: Sulfonylureas; Drug: Thiazolidinediones; Drug: Alpha-glucosidase inhibitors; Drug: Meglitinides | |
| Not currently exposed group | All patients not currently exposed to: incretin-based drugs, insulins, ≥2 OHAs, or a single OHA. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospitalization for incident heart failure
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.
Measured: Patients were followed from the date of study cohort entry until hospitalization for incident heart failure, censoring, or for up to 87 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2015 (estimated)
- Study startMar 2014
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,499,650 participants (actual)
Sponsor and investigators
- Lead sponsor
- Canadian Network for Observational Drug Effect Studies, CNODES
- Sponsor type
- University, hospital or other
- Collaborators
- Drug Safety and Effectiveness Network, Canada, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Pierre Ernst, MD, MSc, Principal investigator, Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456428
- Sponsor's protocol ID
- Q13-06C
- Status last verified
- Apr 2016
- First submitted
- 21 May 2015
- Last updated
- 19 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Filion KB, Azoulay L, Platt RW, Dahl M, Dormuth CR, Clemens KK, Hu N, Paterson JM, Targownik L, Turin TC, Udell JA, Ernst P; CNODES Investigators. A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. N Engl J Med. 2016 Mar 24;374(12):1145-54. doi: 10.1056/NEJMoa1506115.
PubMed 27007958
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incretin-based Drugs and the Risk of Heart Failure: A Multi-center Network Observational Study
- ClinicalTrials.gov ID
- NCT02456428
- Acronym / sponsor ID
- Q13-06C
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Incretins, Antidiabetic Agents, Heart Failure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,499,650 participants (actual)
- Lead sponsor
- Canadian Network for Observational Drug Effect Studies, CNODESUniversity, hospital or other
- Collaborators
- Drug Safety and Effectiveness Network, Canada, Canadian Institutes of Health Research (CIHR)
- Study start
- Mar 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 28 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 heart failure (HF) in routine clinical practice. The investigators will use a common-protocol approach 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 the 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.
For the purpose of this study, two separate cohorts will be created based on the presence or absence of a history of HF at any time prior to and including the date of study cohort entry. Patients in each 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 cohorts defined above will be analyzed using a nested case-control analysis, where cases are defined as a hospitalization for HF. 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 with 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
All analyses will be conducted separately among patients with and without a history of HF. Conditional logistic regression will be used to estimate the odds ratios and corresponding 95% confidence intervals (CIs) of the association of hospitalization for HF, comparing current use of incretin-based drugs to 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 a history of myocardial infarction (MI) will also be explored. 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 in the sensitivity analyses. The amount of between-site heterogeneity will be estimated using the I square statistic.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treated with incretins | – | Drug: DPP-4 inhibitors, Drug: GLP-1 analogsCurrent 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). |
| Treated with insulin | – | Drug: InsulinsCurrent 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. |
| Treated with ≥2 oral hypoglycemic agents | – | Drug: Biguanides, Drug: Sulfonylureas, Drug: Thiazolidinediones, Drug: Alpha-glucosidase inhibitors, Drug: MeglitinidesCurrent 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. |
| Treated with single oral agent | – | Drug: Biguanides, Drug: Sulfonylureas, Drug: Thiazolidinediones, Drug: Alpha-glucosidase inhibitors, Drug: MeglitinidesCurrent 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. |
| Not currently exposed group | – | –All patients not currently exposed to: incretin-based drugs, insulins, ≥2 OHAs, or a single OHA. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DPP-4 inhibitorsAlso: incretin-based drugs, sitagliptin, vildagliptin, saxagliptinCurrent 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. | Drug | Treated with incretins |
| GLP-1 analogsAlso: incretin-based drugs, exenatide, liraglutideCurrent 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. | Drug | Treated with incretins |
| InsulinsAlso: insulins and analogues for injection, fast-acting, insulins and analogues for injection, intermediate-acting, insulins and analogues for injection, long-acting, insulins and analogues for inhalationCurrent exposure to insulin (ATC A10A) will be defined as any use of insulin between base cohort entry and the index day. | Drug | Treated with insulin |
| BiguanidesAlso: oral hypoglycemic agent, phenformin, metformin, buforminCurrent 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. | Drug | Treated with single oral agent, Treated with ≥2 oral hypoglycemic agents |
| SulfonylureasAlso: oral hypoglycemic agent, glibenclamide, chlorpropamide, tolbutamideCurrent 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. | Drug | Treated with single oral agent, Treated with ≥2 oral hypoglycemic agents |
| ThiazolidinedionesAlso: oral hypoglycemic agent, troglitazone, rosiglitazone, pioglitazoneCurrent 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. | Drug | Treated with single oral agent, Treated with ≥2 oral hypoglycemic agents |
| Alpha-glucosidase inhibitorsAlso: oral hypoglycemic agent, acarbose, miglitol, vogliboseCurrent 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. | Drug | Treated with single oral agent, Treated with ≥2 oral hypoglycemic agents |
| MeglitinidesAlso: oral hypoglycemic agent, repaglinide, nateglinideCurrent 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. | Drug | Treated with single oral agent, Treated with ≥2 oral hypoglycemic agents |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2016.
- Results publication: PubMed 27007958Filion KB, Azoulay L, Platt RW, Dahl M, Dormuth CR, Clemens KK, Hu N, Paterson JM, Targownik L, Turin TC, Udell JA, Ernst P; CNODES Investigators. A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. N Engl J Med. 2016 Mar 24;374(12):1145-54. doi: 10.1056/NEJMoa1506115.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre Ernst, MD, MSc principal investigator
Lady Davis Institute for Medical Research, Jewish General Hospital - McGill University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes Mellitus, run by Canadian Network for Observational Drug Effect Studies, CNODES at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02456428, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2016.