Type 2 Diabetes, Cardiac Disease
Conditions
Keywords
Diabetes, Type 2 diabetes, Cardiovascular disease, Comparative effectiveness
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.
Interventions
DRUGGlucagon like peptide 1 receptor agonist
Patients in the data who filled a glucagon-like peptide-1 receptor agonist medication
Patients in the data who filled a sodium-glucose cotransporter 2 inhibitor
Patients in the data who filled a dipeptidyl peptidase-4 inhibitor
DRUGSulfonylurea
Patients in the data who filled a sulfonylurea
Sponsors
Patient-Centered Outcomes Research Institute
Mayo Clinic
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-point Major Adverse Cardiovascular Event (MACE) | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | 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. |
| Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | 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. |
| Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | 1 hour | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe Hypoglycemia | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of emergency department visits or hospitalization for hypoglycemia experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio. |
| Treatment for Diabetic Retinopathy or Macular Edema | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of treatment for diabetic retinopathy and/or macular edema experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio. |
| Non-fatal Myocardial Infarction (MI) | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of a non-fatal MI experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio. |
| Lower Extremity Complications | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of foot and/or leg amputation, osteomyelitis, ulcer, abscess or Charcot arthropathy experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio. |
| Incident End-stage Kidney Disease | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of a new diagnosis of stage 5 or end-stage kidney disease experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio. |
| Non-fatal Stroke Events | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of non-fatal stroke events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio. |
| All-cause Mortality | Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period | The probability of all-cause mortality events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio. |
Countries
United States
Participant flow
Pre-assignment details
Participants in the arm Aims 1, 2B, and 3 groups, were considered enrolled in the trial even though 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.
Participants by arm
| Arm | Count |
|---|---|
| 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) were 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. The 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.
Glucagon like peptide 1 receptor agonist: Patients in the data who filled a glucagon-like peptide-1 receptor agonist medication
Sodium-glucose cotransporter 2 inhibitor: Patients in the data who filled a sodium-glucose cotransporter 2 inhibitor
Dipeptidyl Peptidase 4 Inhibitor: Patients in the data who filled a dipeptidyl peptidase-4 inhibitor
Sulfonylurea: Patients in the data who filled a sulfonylurea | 386,276 |
| 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 received 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. | 25 |
| Total | 386,301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 5,924 | 0 |
Baseline characteristics
| Characteristic | Aims 1, 2B, and 3 Groups | Aim 2A Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 254490 Participants | 6 Participants | 254496 Participants |
| Age, Categorical Between 18 and 65 years | 131786 Participants | 19 Participants | 131805 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33165 Participants | 5 Participants | 33170 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 341028 Participants | 19 Participants | 341047 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12083 Participants | 1 Participants | 12084 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10982 Participants | 0 Participants | 10982 Participants |
| Race (NIH/OMB) Black or African American | 39454 Participants | 1 Participants | 39455 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 50266 Participants | 4 Participants | 50270 Participants |
| Race (NIH/OMB) White | 285574 Participants | 20 Participants | 285594 Participants |
| Region of Enrollment United States | 386276 participants | 25 participants | 386301 participants |
| Sex: Female, Male Female | 190394 Participants | 13 Participants | 190407 Participants |
| Sex: Female, Male Male | 195882 Participants | 12 Participants | 195894 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22,208 / 386,276 | 0 / 25 |
| other Total, other adverse events | 62,982 / 386,276 | 0 / 25 |
| serious Total, serious adverse events | 40,642 / 386,276 | 0 / 25 |
Outcome results
Primary
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.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 380352 total participants were analyzed. Those 380352 participants were further broken down into the following categories DPP4i (82438), GLP-1RA (44255), SGLT2i (46473), Sulfonylureas (SU) (207186), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | 3-point Major Adverse Cardiovascular Event (MACE) | GLP-1RA versus DPP4i | 0.87 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | 3-point Major Adverse Cardiovascular Event (MACE) | SGLT2i versus DPP4i | 0.85 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | 3-point Major Adverse Cardiovascular Event (MACE) | SU versus DPP4i | 1.19 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | 3-point Major Adverse Cardiovascular Event (MACE) | SGLT2i versus GLP-1RA | 0.97 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | 3-point Major Adverse Cardiovascular Event (MACE) | SU versus GLP-1RA | 1.36 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | 3-point Major Adverse Cardiovascular Event (MACE) | SU versus SGLT2i | 1.40 Hazard Ratio |
Primary
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.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 380352 total participants were analyzed. Those 380352 participants were further broken down into the following categories DPP4i (82438), GLP-1RA (44255), SGLT2i (46473), Sulfonylureas (SU) (207186), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | SGLT2i versus DPP4i | 0.93 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | SU versus DPP4i | 1.14 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | SGLT2i versus GLP-1RA | 0.97 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | SU versus GLP-1RA | 1.20 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | SU versus SGLT2i | 1.24 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Expanded Major Adverse Cardiovascular Events (MACE) and Its Components | GLP-1RA versus DPP4i | 0.95 Hazard Ratio |
Primary
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.
Time frame: 1 hour
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Worsening Kidney Function | 4 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Very low blood sugar | 4 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Cancer | 7 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Vessel Blockages | 7 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Stroke | 7 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Amputation | 10 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Heart Attack | 10 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Eye Issues | 4 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Death | 12 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | End Stage Kidney Disease (ESKD) | 11 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Heart Failure | 13 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Blindness | 16 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Serious Infection | 2 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Being admitted | 2 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Pancreatitis | 3 Participants |
| Aims 1, 2B, and 3 Groups | Patient Preferences for Second-line Type 2 Diabetes Medication Treatment Outcomes | Issues with your feet | 4 Participants |
Secondary
All-cause Mortality
The probability of all-cause mortality events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 380352 total participants were analyzed. Those 380352 participants were further broken down into the following categories DPP4i (82438), GLP-1RA (44255), SGLT2i (46473), Sulfonylureas (SU) (207186), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | All-cause Mortality | GLP-1RA versus DPP4i | 0.86 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | All-cause Mortality | SGLT2i versus DPP4i | 0.79 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | All-cause Mortality | SU versus DPP4i | 1.22 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | All-cause Mortality | SGLT2i versus GLP-1RA | 0.92 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | All-cause Mortality | SU versus GLP-1RA | 1.42 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | All-cause Mortality | SU versus SGLT2i | 1.55 Hazard Ratio |
Secondary
Incident End-stage Kidney Disease
The probability of a new diagnosis of stage 5 or end-stage kidney disease experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 367452 total participants were analyzed. Those 367452 participants were further broken down into the following categories DPP4i (77042), GLP-1RA (42009), SGLT2i (53435), Sulfonylureas (SU) (194966), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Incident End-stage Kidney Disease | SGLT2i versus DPP4i | 0.65 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Incident End-stage Kidney Disease | GLP-1RA versus DPP4i | 0.81 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Incident End-stage Kidney Disease | SU versus DPP4i | 1.01 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Incident End-stage Kidney Disease | SGLT2i versus SU | 0.65 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Incident End-stage Kidney Disease | GLP-1RA versus SU | 0.80 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Incident End-stage Kidney Disease | SGLT2i versus GLP-1RA | 0.81 Hazard Ratio |
Secondary
Lower Extremity Complications
The probability of foot and/or leg amputation, osteomyelitis, ulcer, abscess or Charcot arthropathy experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 384451 total participants were analyzed. Those 384451 participants were further broken down into the following categories DPP4i (83937), GLP-1RA (43947), SGLT2i (46926), Sulfonylureas (SU) (209641), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Lower Extremity Complications | SU versus DPP4i | 1.15 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Lower Extremity Complications | SU versus GLP-1RA | 1.20 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Lower Extremity Complications | SU versus SGLT2i | 1.08 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Lower Extremity Complications | SGLT2i versus GLP-1RA | 1.11 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Lower Extremity Complications | GLP-1RA versus DPP4i | 0.96 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Lower Extremity Complications | SGLT2i versus DPP4i | 1.07 Hazard Ratio |
Secondary
Non-fatal Myocardial Infarction (MI)
The probability of a non-fatal MI experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 380352 total participants were analyzed. Those 380352 participants were further broken down into the following categories DPP4i (82438), GLP-1RA (44255), SGLT2i (46473), Sulfonylureas (SU) (207186), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Non-fatal Myocardial Infarction (MI) | GLP-1RA versus DPP4i | 0.89 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Myocardial Infarction (MI) | SGLT2i versus DPP4i | 0.93 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Myocardial Infarction (MI) | SU versus DPP4i | 1.21 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Myocardial Infarction (MI) | SGLT2i versus GLP-1RA | 1.05 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Myocardial Infarction (MI) | SU versus GLP-1RA | 1.35 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Myocardial Infarction (MI) | SU versus SGLT2i | 1.30 Hazard Ratio |
Secondary
Non-fatal Stroke Events
The probability of non-fatal stroke events experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylureas (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 380352 total participants were analyzed. Those 380352 participants were further broken down into the following categories DPP4i (82438), GLP-1RA (44255), SGLT2i (46473), Sulfonylureas (SU) (207186), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Non-fatal Stroke Events | GLP-1RA versus DPP4i | 0.89 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Stroke Events | SGLT2i versus DPP4i | 0.89 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Stroke Events | SU versus DPP4i | 1.18 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Stroke Events | SGLT2i versus GLP-1RA | 1.00 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Stroke Events | SU versus GLP-1RA | 1.33 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Non-fatal Stroke Events | SU versus SGLT2i | 1.33 Hazard Ratio |
Secondary
Severe Hypoglycemia
The probability of emergency department visits or hospitalization for hypoglycemia experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 380352 total participants were analyzed. Those 380352 participants were further broken down into the following categories DPP4i (82438), GLP-1RA (44255), SGLT2i (46473), Sulfonylureas (SU) (207186), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Severe Hypoglycemia | GLP-1RA versus DPP4i | 0.63 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Severe Hypoglycemia | SGLT2i versus DPP4i | 0.56 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Severe Hypoglycemia | SU versus DPP4i | 2.51 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Severe Hypoglycemia | SGLT2i versus GLP-1RA | 0.90 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Severe Hypoglycemia | SU versus GLP-1RA | 4.00 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Severe Hypoglycemia | SU versus SGLT2i | 4.46 Hazard Ratio |
Secondary
Treatment for Diabetic Retinopathy or Macular Edema
The probability of treatment for diabetic retinopathy and/or macular edema experienced by subjects treated with DPP4i, GLP-1RA, SGLT2i, or Sulfonylurea (SU). The probability was calculated and reported as the hazard ratio.
Time frame: Retrospective Data between 1/1/2014 - 12/31/2022, up to 8 years, collected over a 2-year period
Population: 371698 total participants were analyzed. Those 371698 participants were further broken down into the following categories DPP4i (78444), GLP-1RA (42265), SGLT2i (53476), Sulfonylureas (SU) (197513), respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aims 1, 2B, and 3 Groups | Treatment for Diabetic Retinopathy or Macular Edema | SGLT2i versus GLP-1RA | 0.73 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Treatment for Diabetic Retinopathy or Macular Edema | SGLT2i versus DPP4i | 0.79 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Treatment for Diabetic Retinopathy or Macular Edema | SGLT2i versus SU | 0.61 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Treatment for Diabetic Retinopathy or Macular Edema | GLP-1RA versus DPP4i | 1.07 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Treatment for Diabetic Retinopathy or Macular Edema | GLP-1RA versus SU | 0.83 Hazard Ratio |
| Aims 1, 2B, and 3 Groups | Treatment for Diabetic Retinopathy or Macular Edema | SU versus DPP4i | 1.29 Hazard Ratio |