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| ID | Type | Description | Link |
|---|---|---|---|
| NSTC 113-2314-B-040-026-MY2 | Other Grant/Funding Number | National Science and Technology Council, Taiwan | |
| NSTC 114-2622-B-040-001 | Other Grant/Funding Number | National Science and Technology Council, Taiwan | |
| CSH-2025-C-012 | Other Grant/Funding Number | Chung Shan Medical University Hospital | |
| CSH-2025-C-023 | Other Grant/Funding Number | Chung Shan Medical University Hospital |
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| Name | Class |
|---|---|
| National Science and Technology Council, Taiwan | OTHER_GOV |
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This retrospective observational target-trial emulation uses electronic health record data from the TriNetX US Collaborative Network to compare early treatment intensification strategies in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiate a GLP-1 receptor agonist or an SGLT2 inhibitor. The study compares patients who, within 90 days of starting background therapy, add the alternate agent, add a DPP-4 inhibitor or sulfonylurea, or do not receive early add-on therapy. The primary outcome is all-cause mortality over 36 months, with secondary cardiorenal outcomes also evaluated. Propensity-score methods are used to reduce bias from nonrandom treatment selection.
This study is a retrospective observational target-trial emulation using electronic health record data from the TriNetX US Collaborative Network. It evaluates early treatment intensification strategies after initiation of a GLP-1 receptor agonist or an SGLT2 inhibitor in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Patients are grouped according to treatment changes made within 90 days after treatment initiation, including addition of the alternate drug class, addition of a DPP-4 inhibitor or sulfonylurea, or no early add-on treatment. Follow-up is aligned across comparison groups after this initial treatment assessment period.
The study uses routinely collected clinical data to assess the comparative effectiveness of these strategies on mortality and cardiorenal outcomes in real-world practice. Propensity-score-based methods are used to reduce confounding associated with nonrandom treatment selection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GLP-1 RA Base Therapy | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy after a 6-month washout from GLP-1 RA, SGLT2i, DPP-4i, and sulfonylureas. Within this cohort, participants were classified by the first add-on treatment within 90 days into three mutually exclusive strategies: SGLT2i add-on, DPP-4i or sulfonylurea add-on, or no early add-on. |
| |
| SGLT2i Base Therapy | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy after a 6-month washout from GLP-1 RA, SGLT2i, DPP-4i, and sulfonylureas. Within this cohort, participants were classified by the first add-on treatment within 90 days into three mutually exclusive strategies: GLP-1 RA add-on, DPP-4i or sulfonylurea add-on, or no early add-on. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-1 receptor agonist | Drug | Use of a glucagon-like peptide-1 receptor agonist as background therapy or add-on therapy in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause Mortality (Comparison 1) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| All-cause Mortality (Comparison 2) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| All-cause Mortality (Comparison 3) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| All-cause Mortality (Comparison 4) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Major Adverse Cardiovascular Events (MACE) (Comparison 1) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
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Inclusion Criteria:
Exclusion Criteria:
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Adults (≥20 years) with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 identified from routinely collected electronic health record data in the TriNetX US Collaborative Network. Participants initiated a GLP-1 receptor agonist or an SGLT2 inhibitor and were classified according to early add-on treatment strategies.
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39651970 | Background | American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S207-S238. doi: 10.2337/dc25-S010. | |
| 40371589 | Background | Baker-Smith CM, Gauen AM, Petito LC, Khan SS, Allen NB. Prevalence of Cardiovascular-Kidney-Metabolic Stages in US Adolescents and Relationship to Social Determinants of Health. J Am Heart Assoc. 2025 May 20;14(10):e040269. doi: 10.1161/JAHA.124.040269. Epub 2025 May 15. |
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Individual participant data will not be shared. This retrospective observational study uses electronic health record data from the TriNetX US Collaborative Network. Access to individual-level data is restricted by data use agreements, institutional policies, and participant privacy protections.
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Eligibility criteria were applied at cohort identification. The index date (T0) was the first qualifying base-therapy prescription (GLP-1 RA or SGLT2i) after the 6-month washout; each participant was therefore assigned to a single base-therapy arm, and participants are unique across the two arms. Treatment strategies within each arm were classified by first add-on within 90 days of T0. Total Started reflects the unique number enrolled.
Participants were identified retrospectively from the TriNetX US Collaborative Network electronic health record database during the prespecified study period. Eligible adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated background therapy were assessed for inclusion in the study cohort.
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| ID | Title | Description |
|---|---|---|
| FG000 | GLP-1 RA Base Therapy | Adults with obesity, T2D, CKM stage 2-3 who initiated a GLP-1 RA as base therapy after eligibility screening (6-month washout from GLP-1 RA, SGLT2i, DPP-4i, sulfonylureas). Within-arm treatment strategies are reported as Milestones below. |
| FG001 | SGLT2i Base Therapy |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 11, 2026 |
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| SGLT2 inhibitor | Drug | Use of a sodium-glucose cotransporter-2 inhibitor as background therapy or add-on therapy in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. |
|
| Major Adverse Cardiovascular Events (MACE) (Comparison 2) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Major Adverse Cardiovascular Events (MACE) (Comparison 3) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Major Adverse Cardiovascular Events (MACE) (Comparison 4) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Major Adverse Kidney Events (MAKE) (Comparison 1) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Major Adverse Kidney Events (MAKE) (Comparison 2) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Major Adverse Kidney Events (MAKE) (Comparison 3) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
| Major Adverse Kidney Events (MAKE) (Comparison 4) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | From index through 36 months |
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| 40014670 | Background | Rao SV, O'Donoghue ML, Ruel M, Rab T, Tamis-Holland JE, Alexander JH, Baber U, Baker H, Cohen MG, Cruz-Ruiz M, Davis LL, de Lemos JA, DeWald TA, Elgendy IY, Feldman DN, Goyal A, Isiadinso I, Menon V, Morrow DA, Mukherjee D, Platz E, Promes SB, Sandner S, Sandoval Y, Schunder R, Shah B, Stopyra JP, Talbot AW, Taub PR, Williams MS. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025 Apr;151(13):e771-e862. doi: 10.1161/CIR.0000000000001309. Epub 2025 Feb 27. |
| 37622663 | Background | Marx N, Federici M, Schutt K, Muller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023 Oct 14;44(39):4043-4140. doi: 10.1093/eurheartj/ehad192. No abstract available. |
| 37807920 | Background | Ndumele CE, Neeland IJ, Tuttle KR, Chow SL, Mathew RO, Khan SS, Coresh J, Baker-Smith CM, Carnethon MR, Despres JP, Ho JE, Joseph JJ, Kernan WN, Khera A, Kosiborod MN, Lekavich CL, Lewis EF, Lo KB, Ozkan B, Palaniappan LP, Patel SS, Pencina MJ, Powell-Wiley TM, Sperling LS, Virani SS, Wright JT, Rajgopal Singh R, Elkind MSV, Rangaswami J; American Heart Association. A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association. Circulation. 2023 Nov 14;148(20):1636-1664. doi: 10.1161/CIR.0000000000001186. Epub 2023 Oct 9. |
| 38103820 | Background | Sebastian SA, Padda I, Johal G. Cardiovascular-Kidney-Metabolic (CKM) syndrome: A state-of-the-art review. Curr Probl Cardiol. 2024 Feb;49(2):102344. doi: 10.1016/j.cpcardiol.2023.102344. Epub 2023 Dec 14. |
| 37807924 | Background | Ndumele CE, Rangaswami J, Chow SL, Neeland IJ, Tuttle KR, Khan SS, Coresh J, Mathew RO, Baker-Smith CM, Carnethon MR, Despres JP, Ho JE, Joseph JJ, Kernan WN, Khera A, Kosiborod MN, Lekavich CL, Lewis EF, Lo KB, Ozkan B, Palaniappan LP, Patel SS, Pencina MJ, Powell-Wiley TM, Sperling LS, Virani SS, Wright JT, Rajgopal Singh R, Elkind MSV; American Heart Association. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023 Nov 14;148(20):1606-1635. doi: 10.1161/CIR.0000000000001184. Epub 2023 Oct 9. |
Adults with obesity, T2D, CKM stage 2-3 who initiated an SGLT2i as base therapy after eligibility screening (6-month washout from GLP-1 RA, SGLT2i, DPP-4i, sulfonylureas). Within-arm treatment strategies are reported as Milestones below. |
| COMPLETED |
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| NOT COMPLETED |
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Baseline characteristics are presented for each prespecified pairwise propensity score-matched cohort. For each row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | GLP-1 RA With SGLT2i Add-On (Comparison 1) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and were classified as having SGLT2 inhibitor add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 1. |
| BG001 | GLP-1 RA With DPP-4i/SU Add-On (Comparison 1) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and were classified as having DPP-4 inhibitor or sulfonylurea add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 1. |
| BG002 | GLP-1 RA With SGLT2i Add-On (Comparison 2) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and were classified as having SGLT2 inhibitor add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 2. |
| BG003 | GLP-1 RA Only (No Early Add-On) (Comparison 2) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and did not receive early add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 2. |
| BG004 | SGLT2i With GLP-1 RA Add-On (Comparison 3) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and were classified as having GLP-1 receptor agonist add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 3. |
| BG005 | SGLT2i With DPP-4i/SU Add-On (Comparison 3) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and were classified as having DPP-4 inhibitor or sulfonylurea add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 3. |
| BG006 | SGLT2i With GLP-1 RA Add-On (Comparison 4) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and were classified as having GLP-1 receptor agonist add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 4. |
| BG007 | SGLT2i Only (No Early Add-On) (Comparison 4) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and did not receive early add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 4. |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each row, counts are reported only for the two arms in that comparison; remaining columns are 0 because those participants are outside the matched cohort. Cohort eligibility required age ≥20 years; participants not resolved into the displayed age strata are reported under "Other age category" so counts sum to the analyzed population. | Count of Participants | Participants |
| ||||||||||
| Sex/Gender, Customized | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each row, counts are reported only for the two arms in that comparison; remaining columns are 0 because those participants are outside the matched cohort. Participants not resolved into the displayed sex/gender strata are reported under "Unknown or Not Reported" so counts sum to the analyzed population. | Count of Participants | Participants |
| ||||||||||
| Ethnicity (NIH/OMB) | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each row, counts are reported only for the two arms in that comparison; remaining columns are 0 because those participants are outside the matched cohort. Participants not in the listed race strata, including small race groups not shown separately and records without a resolved race category, are reported under "Other, Unknown, or Not Reported" so counts sum to the analyzed population. | Count of Participants | Participants |
| ||||||||||
| CKD | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
| ||||||||||
| Hypertension | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
| ||||||||||
| Dyslipidemia | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
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| Tobacco Use | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
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| BMI ≥30 kg/m2 | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
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| SBP ≥140 mmHg | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
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| HbA1c ≥7% | Data are reported separately for each prespecified pairwise propensity score-matched cohort. For each comparison-specific row, counts are reported only for the two arms that constitute that comparison; the remaining columns are presented as 0 because those participants are outside the matched cohort being characterized in that row. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | All-cause Mortality (Comparison 1) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
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| Primary | All-cause Mortality (Comparison 2) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
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| Primary | All-cause Mortality (Comparison 3) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Primary | All-cause Mortality (Comparison 4) | All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
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| Secondary | Major Adverse Cardiovascular Events (MACE) (Comparison 1) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
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| Secondary | Major Adverse Cardiovascular Events (MACE) (Comparison 2) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Cardiovascular Events (MACE) (Comparison 3) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Cardiovascular Events (MACE) (Comparison 4) | Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Kidney Events (MAKE) (Comparison 1) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Kidney Events (MAKE) (Comparison 2) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Kidney Events (MAKE) (Comparison 3) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
| |||||||||||||||||||||||||||||||
| Secondary | Major Adverse Kidney Events (MAKE) (Comparison 4) | Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3. | Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population. | Posted | Number | participants with event | From index through 36 months |
|
From index date through 36 months of follow-up
Adverse event information was derived from routinely collected EHR data during 36 months of follow-up in this retrospective analysis. Systematic clinical trial AE surveillance was not conducted. AE assessment was limited to all-cause mortality and prespecified EHR-defined serious clinical events, including MACE and MAKE. Other non-serious AEs were not assessed.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GLP-1 RA With SGLT2i Add-On (Comparison 1) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and were classified as having SGLT2 inhibitor add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 1. | 291 | 16,864 | 754 | 16,796 | 0 | 0 |
| EG001 | GLP-1 RA With DPP-4i/SU Add-On (Comparison 1) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and were classified as having DPP-4 inhibitor or sulfonylurea add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 1. | 444 | 16,827 | 983 | 16,734 | 0 | 0 |
| EG002 | GLP-1 RA With SGLT2i Add-On (Comparison 2) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and were classified as having SGLT2 inhibitor add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 2. | 674 | 39,552 | 1,862 | 39,392 | 0 | 0 |
| EG003 | GLP-1 RA Only (No Early Add-On) (Comparison 2) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy and did not receive early add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 2. | 877 | 39,518 | 2,073 | 39,243 | 0 | 0 |
| EG004 | SGLT2i With GLP-1 RA Add-On (Comparison 3) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and were classified as having GLP-1 receptor agonist add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 3. | 352 | 18,850 | 854 | 18,771 | 0 | 0 |
| EG005 | SGLT2i With DPP-4i/SU Add-On (Comparison 3) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and were classified as having DPP-4 inhibitor or sulfonylurea add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 3. | 562 | 18,941 | 1,223 | 18,868 | 0 | 0 |
| EG006 | SGLT2i With GLP-1 RA Add-On (Comparison 4) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and were classified as having GLP-1 receptor agonist add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 4. | 593 | 34,963 | 1,495 | 34,819 | 0 | 0 |
| EG007 | SGLT2i Only (No Early Add-On) (Comparison 4) | Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy and did not receive early add-on treatment within 90 days during the initial treatment assessment period. This group represents the propensity score-matched cohort for Comparison 4. | 770 | 34,987 | 1,727 | 34,827 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Major Adverse Cardiovascular Events | Cardiac disorders | Non-systematic Assessment | Composite EHR-defined cardiovascular outcome assessed separately within each prespecified pairwise comparison during 36 months of follow-up. |
| |
| Major Adverse Kidney Events | Renal and urinary disorders | Non-systematic Assessment | Composite EHR-defined kidney outcome assessed separately within each prespecified pairwise comparison during 36 months of follow-up. |
|
Not provided
This retrospective observational target-trial emulation is subject to residual confounding, misclassification, and missing or incomplete electronic health record data. Treatment strategies were not randomly assigned, and matching was performed separately for each pairwise comparison.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yu-Nan Huang, Ph.D. | Chung Shan Medical University Hospital | 886-4-24739595 | 21707 | yunanhuang83@gmail.com |
| May 24, 2026 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077203 | Sodium-Glucose Transporter 2 Inhibitors |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D007004 | Hypoglycemic Agents |
| D045505 | Physiological Effects of Drugs |
Not provided
Not provided
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| 45-64 years (Comparison 1) |
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| 65-74 years (Comparison 1) |
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| ≥75 years (Comparison 1) |
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| Other age category (Comparison 1) |
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| 20-44 years (Comparison 2) |
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| 45-64 years (Comparison 2) |
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| 65-74 years (Comparison 2) |
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| ≥75 years (Comparison 2) |
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| Other age category (Comparison 2) |
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| 20-44 years (Comparison 3) |
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| 45-64 years (Comparison 3) |
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| 65-74 years (Comparison 3) |
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| ≥75 years (Comparison 3) |
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| Other age category (Comparison 3) |
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| 20-44 years (Comparison 4) |
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| 45-64 years (Comparison 4) |
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| 65-74 years (Comparison 4) |
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| ≥75 years (Comparison 4) |
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| Other age category (Comparison 4) |
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| Female (Comparison 1) |
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| Unknown or Not Reported (Comparison 1) |
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| Male (Comparison 2) |
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| Female (Comparison 2) |
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| Unknown or Not Reported (Comparison 2) |
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| Male (Comparison 3) |
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| Female (Comparison 3) |
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| Unknown or Not Reported (Comparison 3) |
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| Male (Comparison 4) |
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| Female (Comparison 4) |
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| Unknown or Not Reported (Comparison 4) |
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| Comparison 2 |
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| Comparison 3 |
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| Comparison 4 |
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| Black or African American (Comparison 1) |
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| Asian (Comparison 1) |
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| Other Races (Comparison 1) |
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| Other, Unknown, or Not Reported (Comparison 1) |
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| White (Comparison 2) |
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| Black or African American (Comparison 2) |
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| Asian (Comparison 2) |
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| Other Races (Comparison 2) |
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| Other, Unknown, or Not Reported (Comparison 2) |
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| White (Comparison 3) |
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| Black or African American (Comparison 3) |
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| Asian (Comparison 3) |
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| Other Races (Comparison 3) |
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| Other, Unknown, or Not Reported (Comparison 3) |
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| White (Comparison 4) |
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| Black or African American (Comparison 4) |
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| Asian (Comparison 4) |
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| Other Races (Comparison 4) |
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| Other, Unknown, or Not Reported (Comparison 4) |
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| CKD (Comparison 2) |
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| CKD (Comparison 3) |
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| CKD (Comparison 4) |
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| Hypertension (Comparison 2) |
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| Hypertension (Comparison 3) |
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| Hypertension (Comparison 4) |
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| Dyslipidemia (Comparison 2) |
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| Dyslipidemia (Comparison 3) |
|
|
| Dyslipidemia (Comparison 4) |
|
|
|
| Tobacco Use (Comparison 2) |
|
|
| Tobacco Use (Comparison 3) |
|
|
| Tobacco Use (Comparison 4) |
|
|
|
| BMI ≥30 kg/m2 (Comparison 2) |
|
|
| BMI ≥30 kg/m2 (Comparison 3) |
|
|
| BMI ≥30 kg/m2 (Comparison 4) |
|
|
|
| SBP ≥140 mmHg (Comparison 2) |
|
|
| SBP ≥140 mmHg (Comparison 3) |
|
|
| SBP ≥140 mmHg (Comparison 4) |
|
|
|
| HbA1c ≥7% (Comparison 2) |
|
|
| HbA1c ≥7% (Comparison 3) |
|
|
| HbA1c ≥7% (Comparison 4) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|