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

NCT05214573 | Completed Results

• 1 other identifier: 21-007688
• Study Type: observational
• Target: 386,301
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Cardiac Disease

Keywords

Diabetes; Type 2 diabetes; Cardiovascular disease; Comparative effectiveness

Outcome Measures

Primary Outcomes (3)

• 3-point Major Adverse Cardiovascular Event (MACE)

  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.

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

• Expanded Major Adverse Cardiovascular Events (MACE) and Its Components

  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.

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

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

  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.

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Secondary Outcomes (7)

• 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

Study Arms (2)

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.

Drug: Glucagon like peptide 1 receptor agonist; Drug: Sodium-glucose cotransporter 2 inhibitor; Drug: Dipeptidyl Peptidase 4 Inhibitor; Drug: 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 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.

Interventions

Glucagon like peptide 1 receptor agonist DRUG

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

Aims 1, 2B, and 3 Groups

Sodium-glucose cotransporter 2 inhibitor DRUG

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

Aims 1, 2B, and 3 Groups

Dipeptidyl Peptidase 4 Inhibitor DRUG

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

Aims 1, 2B, and 3 Groups

Sulfonylurea DRUG

Patients in the data who filled a sulfonylurea

Aims 1, 2B, and 3 Groups

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Aims 1, 2B, 3: De-identified data sets using laboratory results, electronic health record and mortality data from the OptumLabs Data Warehouse (OLDW) and Medicare fee-for-service data. Aim 2A: Adults with Type 2 diabetes receiving care from primary care and endocrinology practices in Mayo Clinic Rochester, MN or Mayo Clinic Health System in Minnesota and Wisconsin.

You may qualify if:

• ≥ 21 years old.
• Diagnosis of Type 2 diabetes.
• Use of ≥ 1 study drug (GLP-1RA, SGLT2i, DPP-4i, SU).

You may not qualify if:

• 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
• Insulin use.
• Cognitive impairment.
• Terminal or advanced illness.
• Non-English speaking.
• Residency in a long-term care setting.

Sponsors & Collaborators

• Mayo Clinic: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (1)

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Neumiller JJ, Herrin J, Swarna KS, Polley EC, Galindo RJ, Umpierrez GE, Deng Y, Ross JS, Mickelson MM, McCoy RG. Kidney Outcomes with Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk. Clin J Am Soc Nephrol. 2024 Oct 8;20(2):206-17. doi: 10.2215/CJN.0000000587. Online ahead of print.

  PMID: 39729347 DERIVED

• McCoy RG, Herrin J, Swarna KS, Deng Y, Kent DM, Ross JS, Umpierrez GE, Galindo RJ, Crown WH, Borah BJ, Montori VM, Brito JP, Neumiller JJ, Mickelson MM, Polley EC. Effectiveness of glucose-lowering medications on cardiovascular outcomes in patients with type 2 diabetes at moderate cardiovascular risk. Nat Cardiovasc Res. 2024 Apr;3(4):431-440. doi: 10.1038/s44161-024-00453-9. Epub 2024 Apr 3.

  PMID: 38846711 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Heart Diseases; Diabetes Mellitus; Cardiovascular Diseases

Interventions

Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Protease Inhibitors; Enzyme Inhibitors; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Rozalina McCoy, M.D., M.S.
• Organization: Mayo Clinic

mccoy.rozalina@mayo.edu

507-538-7955

Study Officials

• Rozalina McCoy, MD, MS

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: January 28, 2022
• Study Start: December 1, 2021
• Primary Completion: September 30, 2023
• Study Completion: July 22, 2025
• Last Updated: October 10, 2025
• Results First Posted: October 10, 2025

Record last verified: 2025-09

Locations

US (1)