Skip to main content
OpenTrials
Completed

NCT Number: NCT05214573

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Cardiac Disease Cardiovascular Diseases Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Heart Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

21 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

About this study

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.

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for all Aims

  • ≥ 21 years old.
  • Diagnosis of Type 2 diabetes.
  • Use of ≥ 1 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.

Treatment and study plan

Glucagon like peptide 1 receptor agonist

Drug

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

Sodium-glucose cotransporter 2 inhibitor

Drug

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

Dipeptidyl Peptidase 4 Inhibitor

Drug

Patients in the data who filled a dipeptidyl peptidase-4 inhibitor

Sulfonylurea

Drug

Patients in the data who filled a sulfonylurea

Primary outcomes

  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

    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

    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

    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.

Secondary outcomes

  1. Non-fatal Myocardial Infarction (MI)

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

    The probability of a non-fatal MI experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.

  2. Non-fatal Stroke Events

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

    The probability of non-fatal stroke events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.

  3. All-cause Mortality

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

    The probability of all-cause mortality events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.

  4. Severe Hypoglycemia

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

    The probability of emergency department visits or hospitalization for hypoglycemia experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.

  5. Incident End-stage Kidney Disease

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

    The probability of a new diagnosis of stage 5 or end-stage kidney disease experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.

  6. Treatment for Diabetic Retinopathy or Macular Edema

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

    The probability of treatment for diabetic retinopathy and/or macular edema experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.

  7. Lower Extremity Complications

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

    The probability of foot and/or leg amputation, osteomyelitis, ulcer, abscess or Charcot arthropathy experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Collaborators

  • Patient-Centered Outcomes Research Institute

Registry information

Important dates

Study start
2021
Primary completion
2023
Study completion
2025
First posted
Jan 28, 2022
Registry last updated
Oct 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.