Second-line Therapies for Patients With Type 2 Diabetes and Moderate Cardiovascular Disease Risk
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 386,301
- 试验地点
- 1
- 主要终点
- 3-point Major Adverse Cardiovascular Event (MACE)
研究概览
简要总结
We will use the target trial framework for causal inference to conduct this observational retrospective cohort study that uses claims data of adults with type 2 diabetes (T2D) included in the de-identified datasets of OptumLabs Data Warehouse (OLDW) and Medicare fee-for-service.
In Aim 1, we will emulate a target trial comparing the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas (SU) in adults with T2D at moderate risk of cardiovascular disease (CVD) with regard to major adverse cardiovascular events (MACE), expanded MACE, microvascular complications, severe hypoglycemia, and other adverse events.
In Aim 2, we will compare these four drug classes in the same population of adults with T2D included in OLDW and Medicare fee-for-service data with respect to a set of composite outcomes identified by a group of patients with T2D as being most important to them. Specifically, in Aim 2A, we will prospectively elicit patient preferences toward various treatment outcomes (e.g., hospitalization, kidney disease) using a participatory ranking exercise, then use these rankings to generate individually weighted composite outcomes. Then, in Aim 2B, we will estimate patient-centered treatment effects of four different second-line T2D medications that reflect the patient's value for each outcome.
In Aim 3, we will compare different medications within each of the four therapeutic classes with respect to MACE.
详细描述
Study Design: We will use the target trial framework for causal inference to conduct this observational cohort study.
Comparators: Aims 1-2 compare the GLP-1RA, SGLT2i, DPP-4i, and SU classes, while Aim 3 compares the individual drugs within each therapeutic class.
Population: Using data from OptumLabs Data Warehouse linked to 100% Medicare FFS claims, we will identify adults (≥21 years) with T2D at moderate risk for CVD who started a GLP-1RA, SGLT2i, DPP-4i, or SU
Outcomes: In AIMs 1 and 3, the primary outcome will be time to MACE (non-fatal MI, non-fatal stroke, all-cause mortality). Secondary outcomes will include times to expanded MACE (MACE, HF hospitalizations, revascularization procedures) and its components, lower extremity complications, severe hypoglycemia, microvascular complications, and other significant adverse events. In AIM 2A, we will elicit patient preferences toward various treatment outcomes using a participatory ranking exercise, use these rankings to generate individually weighted composite outcomes, and then estimate patient-centered treatment effects of GLP-1RA, SGLT2i, DPP4i, and SU reflecting the patient values for each of the outcomes.
Timeframe: January 1, 2014 to December 31, 2021.
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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Aims 1, 2B, and 3 Groups
De-identified administrative claims with linked laboratory results, electronic health record (EHR), and mortality data from the OptumLabs Data Warehouse (OLDW) and Medicare fee-for-service data (Medicare parts A, B, D) will be utilized to identify adults (≥21 years) with T2D (established using validated Healthcare Effectiveness Data and Information Set criteria) who first filled any study drug GLP-1RA, SGLT2i, DPP-4i, or SU between 1/1/2014-12/31/2021. This arm was exempt from Mayo Clinic Institutional Review Board review and informed consent requirements were not applicable as this arm used deidentified administrative claims data.
干预措施: Glucagon like peptide 1 receptor agonist (Drug)
Aims 1, 2B, and 3 Groups
De-identified administrative claims with linked laboratory results, electronic health record (EHR), and mortality data from the OptumLabs Data Warehouse (OLDW) and Medicare fee-for-service data (Medicare parts A, B, D) will be utilized to identify adults (≥21 years) with T2D (established using validated Healthcare Effectiveness Data and Information Set criteria) who first filled any study drug GLP-1RA, SGLT2i, DPP-4i, or SU between 1/1/2014-12/31/2021. This arm was exempt from Mayo Clinic Institutional Review Board review and informed consent requirements were not applicable as this arm used deidentified administrative claims data.
干预措施: Sodium-glucose cotransporter 2 inhibitor (Drug)
Aims 1, 2B, and 3 Groups
De-identified administrative claims with linked laboratory results, electronic health record (EHR), and mortality data from the OptumLabs Data Warehouse (OLDW) and Medicare fee-for-service data (Medicare parts A, B, D) will be utilized to identify adults (≥21 years) with T2D (established using validated Healthcare Effectiveness Data and Information Set criteria) who first filled any study drug GLP-1RA, SGLT2i, DPP-4i, or SU between 1/1/2014-12/31/2021. This arm was exempt from Mayo Clinic Institutional Review Board review and informed consent requirements were not applicable as this arm used deidentified administrative claims data.
干预措施: Dipeptidyl Peptidase 4 Inhibitor (Drug)
Aims 1, 2B, and 3 Groups
De-identified administrative claims with linked laboratory results, electronic health record (EHR), and mortality data from the OptumLabs Data Warehouse (OLDW) and Medicare fee-for-service data (Medicare parts A, B, D) will be utilized to identify adults (≥21 years) with T2D (established using validated Healthcare Effectiveness Data and Information Set criteria) who first filled any study drug GLP-1RA, SGLT2i, DPP-4i, or SU between 1/1/2014-12/31/2021. This arm was exempt from Mayo Clinic Institutional Review Board review and informed consent requirements were not applicable as this arm used deidentified administrative claims data.
干预措施: Sulfonylurea (Drug)
结局指标
主要结局
3-point Major Adverse Cardiovascular Event (MACE)
时间窗: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
The probability of 3-point MACEs experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU) defined as non-fatal myocardial infarction (MI), non-fatal stroke, and mortality. The probability was calculated and reported as the hazard ratio.
Expanded Major Adverse Cardiovascular Events (MACE) and Its Components
时间窗: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
The probability of 3-point MACEs (non-fatal MI, non-fatal stroke, mortality) plus heart failure hospitalization and revascularization procedure events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.
Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes
时间窗: 1 hour
Patients ranked treatment outcomes using a participatory ranking questionnaire. The questionnaire included a list of 16 health outcomes and eight medication attributes, with opportunities for participants to add outcomes and attributes into the ranking lists. During the exercise, participants were asked to assign each outcome and attribute to one of three mutually exclusive categories: "very important," "somewhat important," or "not very important," based on the degree to which each outcome or attribute would influence their choice of medication. Results shown below reflect the health outcomes/medication attributes that were ranked "very important" by patients.
次要结局
- Non-fatal Myocardial Infarction (MI)(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
- Non-fatal Stroke Events(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
- All-cause Mortality(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
- Severe Hypoglycemia(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
- Incident End-stage Kidney Disease(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
- Treatment for Diabetic Retinopathy or Macular Edema(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
- Lower Extremity Complications(Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period)
研究者
Rozalina G. McCoy
Principal Investigator
Mayo Clinic