Kaiser Permanente
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.
Type 2 Diabetes Mellitus
Cardiovascular Diseases
SU
DPP4
SGLT2i
GLP-1RA
SGLT2i or GLP-1RA
Linagliptin (DPP4)
Exenatide (GLP-1RA)
Liraglutide (GLP-1RA)
Empagliflozin (SGLT2i)
Glimepiride (SU)
Glipizide (SU)
Glimepiride (SU) or Glipizide (SU)
SU or DPP4 (excluding saxagliptin and alogliptin)
Exenatide (GLP-1RA) or Liraglutide (GLP-1RA)
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.
| Study Type : | OBSERVATIONAL |
| Estimated Enrollment : | 270000 participants |
| Official Title : | Comparison of Type 2 Diabetes Pharmacotherapy Regimens Using Targeted Learning |
| Actual Study Start Date : | 2021-07-01 |
| Estimated Primary Completion Date : | 2024-12-31 |
| Estimated Study Completion Date : | 2025-08-31 |
Information not available for Arms and Intervention/treatment
| Ages Eligible for Study: | 18 Years to 85 Years |
| Sexes Eligible for Study: | ALL |
| Accepts Healthy Volunteers: |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
RECRUITING
Romain S. Neugebauer
Oakland, California, United States, 94612
RECRUITING
Kaiser Permanente Southern California
Pasadena, California, United States, 91101
RECRUITING
Kaiser Permanente Hawaii
Honolulu, Hawaii, United States, 96817
RECRUITING
Henry Ford Health System
Detroit, Road cancer, United States, 48202
RECRUITING
HealthPartners Institute
Bloomington, Minnesota, United States, 55425
RECRUITING
Geisinger
Danville, Pennsylvania, United States, 17821