Second-line Therapies for Patients With Type 2 Diabetes and Moderate Cardiovascular Disease Risk

Sponsor
Mayo Clinic (Other)
Overall Status
Enrolling by invitation
CT.gov ID
NCT05214573
Collaborator
Patient-Centered Outcomes Research Institute (Other)
500,000
1
45
11116.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Glucagon like peptide 1 receptor agonist
  • Drug: Sodium-glucose cotransporter 2 inhibitor
  • Drug: Dipeptidyl Peptidase 4 Inhibitor
  • Drug: Sulfonylurea

Detailed Description

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, 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, 2019.

Methods: Inverse probability weighting will be used to emulate baseline randomization for pairwise comparisons between the drug classes (AIMs 1-2) and individual drugs within each class (AIM 3). Causal cumulative incidence rates will be estimated in the weighted sample using the targeted maximum likelihood estimator adjusting for time-dependent confounding and loss-to-follow-up.

Study Design

Study Type:
Observational
Anticipated Enrollment :
500000 participants
Observational Model:
Cohort
Time Perspective:
Retrospective
Official Title:
Second-line Therapies for Patients With Type 2 Diabetes and Moderate Cardiovascular Disease Risk
Actual Study Start Date :
Dec 1, 2021
Anticipated Primary Completion Date :
Aug 31, 2024
Anticipated Study Completion Date :
Aug 31, 2025

Arms and Interventions

Arm Intervention/Treatment
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 1/1/2014-12/31/2020.

Drug: Glucagon like peptide 1 receptor agonist
Patients in the data who filled a glucagon-like peptide-1 receptor agonist medication

Drug: Sodium-glucose cotransporter 2 inhibitor
Patients in the data who filled a sodium-glucose cotransporter 2 inhibitor

Drug: Dipeptidyl Peptidase 4 Inhibitor
Patients in the data who filled a dipeptidyl peptidase-4 inhibitor

Drug: Sulfonylurea
Patients in the data who filled a sulfonylurea

Aim 2A Group

Adults with Type 2 diabetes treated with one or more of the study medications (GLP-1RA, SGLT2i, DPP-4i, or SU) and not treated with insulin who receive medical care at Mayo Clinic Rochester, Mayo Clinic Health System in Minnesota or Wisconsin, or Emory University/Grady Hospital.

Outcome Measures

Primary Outcome Measures

  1. 3-point MACE [1/1/2014 - 12/31/2021]

    Number of 3-point MACE events defined as non-fatal MI, non-fatal stroke, and mortality

Secondary Outcome Measures

  1. Expanded MACE and its components [1/1/2014 - 12/31/2021]

    Number of 3-point MACE (non-fatal MI, non-fatal stroke, mortality) plus heart failure hospitalization and revascularization procedure events

  2. Non-fatal myocardial infarction (MI) [1/1/2014 - 12/31/2021]

    Number of non-fatal myocardial infarctions

  3. Non-fatal stroke events [1/1/2014 - 12/31/2021]

    Number of non-fatal stroke events

  4. All-cause moratality [1/1/2014 - 12/31/2021]

    Number of deaths

  5. Severe hypoglycemia [1/1/2014 - 12/31/2021]

    Number of emergency department visits or hospitalization for hypoglycemia

  6. Incident end-stage kidney disease [1/1/2014 - 12/31/2021]

    Number of initiation of dialysis or new diagnosis of stage 5 or end-stage kidney disease

  7. Treatment for diabetic retinopathy or macular edema [1/1/2014 - 12/31/2021]

    Number of treatments for diabetic retinopathy or macular edema

  8. Lower extremity complications [1/1/2014 - 12/31/2021]

    Number of foot and/or leg amputation, osteomyelitis, ulcer, Charcot arthropathy

  9. All-cause hospitalization [1/1/2014 - 12/31/2021]

    Number of hospitalizations

  10. Severe genitourinary tract infection [1/1/2014 - 12/31/2021]

    Number of severe genitourinary tract infection

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria for all Aims

  • ≥ 21 years old.

  • Diagnosis of Type 2 diabetes.

  • Use of ≥ study drug (GLP-1RA, SGLT2i, DPP-4i, SU).

Exclusion Criteria for Aims 1, 2B, 3

  • Fill for any study drug during the baseline period or simultaneous (within 30 days) start of ≥2 study drugs

  • Insulin use

  • Type 1 diabetes

  • High risk of CVD

  • Pregnancy

  • Metastatic cancer

Exclusion Criteria for Aim 2A

  • Insulin use.

  • Cognitive impairment.

  • Terminal or advanced illness.

  • Non-English speaking.

  • Residency in a long-term care setting.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Mayo Clinic Rochester Rochester Minnesota United States 55905

Sponsors and Collaborators

  • Mayo Clinic
  • Patient-Centered Outcomes Research Institute

Investigators

  • Principal Investigator: Rozalina McCoy, MD, MS, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Rozalina G. McCoy, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT05214573
Other Study ID Numbers:
  • 21-007688
First Posted:
Jan 28, 2022
Last Update Posted:
Jan 28, 2022
Last Verified:
Jan 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Rozalina G. McCoy, Principal Investigator, Mayo Clinic
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 28, 2022