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

Status

Completed

Phase

Phase not stated

Enrollment

386,301 participants (actual)

Sponsor

Mayo Clinic · Other

Design

Not stated

Countries

1 country

United States

Start

1 Dec 2021

Primary completion

30 Sept 2023

Completion

22 Jul 2025

First posted

28 Jan 2022

Last update posted

10 Oct 2025

Conditions

Type 2 Diabetes · Cardiac Disease

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.

• Other

  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.

• Other

  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 or Mayo Clinic Health System in Minnesota or Wisconsin. This arm was not exempt from Mayo Clinic Institutional Review Board review and informed consent requirements were applicable as this arm collected prospective data.

1. 3-point Major Adverse Cardiovascular Event (MACE)

   Time frame · Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period

   Registry description

   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.

2. Expanded Major Adverse Cardiovascular Events (MACE) and Its Components

   Time frame · Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period

   Registry description

   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.

3. Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes

   Time frame · 1 hour

   Registry description

   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.

No study cites this trial.