Incretin-based Drugs and the Risk of Heart Failure: A Multi-center Network Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,499,650
- 试验地点
- 1
- 主要终点
- Hospitalization for incident heart failure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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,
- •Patients diagnosed with HIV or initiating HAART therapy before and at study cohort entry.
研究组 & 干预措施
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).
干预措施: DPP-4 inhibitors (Drug)
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).
干预措施: GLP-1 analogs (Drug)
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.
干预措施: Insulins (Drug)
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.
干预措施: Biguanides (Drug)
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.
干预措施: Sulfonylureas (Drug)
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.
干预措施: Thiazolidinediones (Drug)
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.
干预措施: Alpha-glucosidase inhibitors (Drug)
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.
干预措施: Meglitinides (Drug)
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.
干预措施: Biguanides (Drug)
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.
干预措施: Sulfonylureas (Drug)
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.
干预措施: Thiazolidinediones (Drug)
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.
干预措施: Alpha-glucosidase inhibitors (Drug)
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.
干预措施: Meglitinides (Drug)
结局指标
主要结局
Hospitalization for incident heart failure
时间窗: 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.
次要结局
未报告次要终点