N/A
Completed N=386,301
Second-line Therapies for Patients With Type 2 Diabetes and Moderate Cardiovascular Disease Risk
Source: ClinicalTrials.gov NCT05214573 ↗Enrolled (actual)
386,301
Serious AEs
10.5%
Results posted
Oct 2025
Primary outcomePrimary: 3-point Major Adverse Cardiovascular Event (MACE) — 0.87; 0.85; 1.19; 0.97 Hazard Ratio
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 3-point Major Adverse Cardiovascular Event (MACE) |
0.87; 0.85; 1.19; 0.97; 1.36; 1.40 | — |
| PRIMARY Expanded Major Adverse Cardiovascular Events (MACE) and Its Components |
0.95; 0.93; 1.14; 0.97; 1.20; 1.24 | — |
| PRIMARY Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes |
2; 2; 3; 4; 4; 4 | — |
| SECONDARY Non-fatal Myocardial Infarction (MI) |
0.89; 0.93; 1.21; 1.05; 1.35; 1.30 | — |
| SECONDARY Non-fatal Stroke Events |
0.89; 0.89; 1.18; 1.00; 1.33; 1.33 | — |
| SECONDARY All-cause Mortality |
0.86; 0.79; 1.22; 0.92; 1.42; 1.55 | — |
| SECONDARY Severe Hypoglycemia |
0.63; 0.56; 2.51; 0.90; 4.00; 4.46 | — |
| SECONDARY Incident End-stage Kidney Disease |
0.65; 0.81; 1.01; 0.65; 0.80; 0.81 | — |
| SECONDARY Treatment for Diabetic Retinopathy or Macular Edema |
0.73; 0.79; 0.61; 1.07; 0.83; 1.29 | — |
| SECONDARY Lower Extremity Complications |
1.15; 1.20; 1.08; 1.11; 0.96; 1.07 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT05214573). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.