Clinical trial NCT05073692: Comparison of Type 2 Diabetes Pharmacotherapy Regimens
Official title: Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type 2 Diabetes Mellitus
Cardiovascular Diseases
Keywords: Type 2 Diabetes Mellitus
Cardiovascular Diseases
Medication
Treatment
Lead sponsor: Kaiser Permanente
Sponsor class: OTHER
Collaborators: name: Geisinger Clinic
name: Henry Ford Health System
name: HealthPartners Institute
name: Patient-Centered Outcomes Research Institute
First posted: 2021-10-11
Enrollment: 270000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from six large care delivery systems with integrated administrative and EHR clinical data sources (Geisinger in Pennsylvania, Henry Ford Health System in Michigan, HealthPartners Institute in Minnesota and Wisconsin, and Kaiser Permanente of Northern California, Southern California, and Hawaii) who were new users of glucose-lowering medications between 01/01/2014 and 06/30/2023.

Brief summary: This study is designed to help patients with type 2 diabetes and their clinicians: (a) identify which glucose lowering medications have the most favorable effects on heart health and other patient-important outcomes, (b) inform the timing of medication initiation, and (c) identify whether medication benefits apply equally to all adults with type 2 diabetes, or may be different based on age, sex, race/ethnicity, baseline heart health status, baseline renal function, or other factors.

Detailed description: The study will conduct head-to-head comparisons of type 2 diabetes mellitus (T2DM) treatment strategies using observational data from real-world clinical settings to assess cardiovascular disease (CVD) outcomes and other patient-centered outcomes in T2DM patients with moderate baseline CVD risk who are treated with each of these four classes of glucose-lowering medications known as SGLT2, GLP-1RA, DPP4, and SU. To mitigate bias concerns related to confounding and informative loss to follow-up, analyses will be based on modern causal inference methods combined with machine learning that emulate intention-to-treat (ITT) and per-protocol (PP) analyses of pragmatic randomized trials with active comparators to provide the most robust and precise estimates of relative and absolute effects we would expect in usual care settings.

Specific Aims and Hypotheses:

Aim 1. Compare the effect off SGLT21, GLP-1RA, DPP4, and SU on each study outcome in adults with T2DM when each type of medication is (a) initiated as second-line therapy after metformin, and (b) initiated as first-, second-, or third-line therapy, or after any history of glucose-lowering therapy independent of prior metformin use.

Aim 2. Compare the effect on each study outcome of earlier versus later initiation of SGLT2i, GLP-1RA, DPP4, SU as first-, or second-, or third-line therapy, or after any history of glucose-lowering therapy triggered by various changes in A1C, or CVD risk, or other patient characteristics.

Aim 3. Assess in each of the prior analyses whether the treatment effects on study outcomes vary across categories of baseline CVD risk and CVD event history, renal function, congestive heart failure status, age, sex and race/ethnicity, or other patient characteristics.

Aim 4. Evaluate trends in new pharmacy dispensing of SGLT2i and GLP1-RA between 2014 and 2021, in aggregate and by age, sex, race and ethnicity and concurrent T2DM drug use

Aim 5. Evaluate trends in new pharmacy dispensing of SGLT2i and GLP1-RA between 2014 and 2021, by baseline ASCVD, heart failure and diabetic kidney disease.

Aim 6. Describe primary adherence, secondary adherence, and persistence for diabetes medication

Aim 7. Compare rates of primary non-adherence, secondary adherence, and medication persistence for brand name and generic medications for type 2 diabetes in specific subgroups of patients

Aim 8. Examine trends in medication possession for brand name medications over the course of the calendar year

Glucose-lowering medications will be compared at both the class and agent level. The key outcomes that will be considered are MACE 3-point, Myocardial Infarction, Stroke, Heart Failure, Hospitalization, Coronary or Carotid Artery Stent or Bypass Procedure, CVD Mortality, Overall Mortality. Additional patient-centered outcomes will be specified based on insights from stakeholder members of the research team.

Eligibility criteria: * Dispensing of either of the set of drugs being compared
* No prior dispensing of any of the drugs compared
* Evidence of Type 2 Diabetes Mellitus diagnosis
* Age 18-85
* Not currently pregnant
* No evidence of dementia or short-term life expectancy from prior cancer diagnoses
* History of ≥2 years of continuous health plan membership
* ≥1 A1c test in the past 18 months

Primary outcomes:
measure: Incidence of 3-point Major Adverse Cardiovascular Events (MACE)
timeFrame: 1/1/2014 to 6/30/2021
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Romain S. Neugebauer
state: California
city: Pasadena
country: United States
facility: Kaiser Permanente Southern California
state: California
city: Honolulu
country: United States
facility: Kaiser Permanente Hawaii
state: Hawaii
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Bloomington
country: United States
facility: HealthPartners Institute
state: Minnesota
city: Danville
country: United States
facility: Geisinger
state: Pennsylvania
Study officials:
affiliation: Kaiser Permanente
name: Romain S. Neugebauer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: HealthPartners Institute
name: Patrick J O'Connor, MD, MA, MPH
role: PRINCIPAL_INVESTIGATOR
References: