Clinical trial NCT05214573: Second-line Therapies for Patients with Type 2 Diabetes and Moderate Cardiovascular Disease Risk
Official title: Second-line Therapies for Patients with Type 2 Diabetes and Moderate Cardiovascular Disease Risk
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Type 2 Diabetes
Cardiac Disease
Keywords: Diabetes
Type 2 diabetes
Cardiovascular disease
Comparative effectiveness
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2022-01-28
Enrollment: 500000
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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, Mayo Clinic Health System in Minnesota and Wisconsin, and Emory University/Grady Hospital in Atlanta, GA.

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.

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, 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 3-point MACE
timeFrame: 1/1/2014 - 12/31/2021
Secondary outcomes:
measure: Expanded MACE and its components
timeFrame: 1/1/2014 - 12/31/2021
measure: Non-fatal myocardial infarction (MI)
timeFrame: 1/1/2014 - 12/31/2021
measure: Non-fatal stroke events
timeFrame: 1/1/2014 - 12/31/2021
measure: All-cause moratality
timeFrame: 1/1/2014 - 12/31/2021
measure: Severe hypoglycemia
timeFrame: 1/1/2014 - 12/31/2021
measure: Incident end-stage kidney disease
timeFrame: 1/1/2014 - 12/31/2021
measure: Treatment for diabetic retinopathy or macular edema
timeFrame: 1/1/2014 - 12/31/2021
measure: Lower extremity complications
timeFrame: 1/1/2014 - 12/31/2021
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Rozalina McCoy, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: