Early GLP-1 Receptor Agonist and SGLT2 Inhibitor Add-On Strategies in Adults With Obesity, Type 2 Diabetes, Cardiovascular-Kidney-Metabolic Syndrome Stage 2-3, and Metabolic Dysfunction-Associated Steatotic Liver Disease
28 maggio 2026 aggiornato da: Yu-Nan Huang, Chung Shan Medical University
Early GLP-1 Receptor Agonist and SGLT2 Inhibitor Add-On Strategies in Adults With Obesity, Type 2 Diabetes, Cardiovascular-Kidney-Metabolic Syndrome Stage 2-3, and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Target Trial Emulation
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, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiate a GLP-1 receptor agonist or an SGLT2 inhibitor as background therapy.
Within each background-therapy cohort, patients who added the complementary class within 90 days of initiation were compared against patients who did not, with prespecified comparisons against both the overall non-complementary cohort and the analytical subset who initiated usual-care add-on therapy (DPP-4 inhibitors, sulfonylureas, or insulin) within the same window.
The primary outcome is all-cause mortality over 60 months, with major adverse cardiovascular, kidney, and liver outcomes also evaluated.
Propensity-score matching is used to reduce bias from nonrandom treatment selection.
Panoramica dello studio
Stato
Completato
Tipo di studio
Osservativo
Iscrizione (Effettivo)
118805
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Taichung
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Taichung, Taichung, Taiwan, 402
- Chung Shan Medical University Hospital
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
No
Metodo di campionamento
Campione non probabilistico
Popolazione di studio
Adults will be selected from the TriNetX US Collaborative Network, a distributed database of de-identified electronic health records contributed by participating healthcare organizations across multiple clinical systems and practice settings.
The study population consists of adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who received routine clinical care in this network and were identified through diagnosis records, body mass index data, laboratory data, and medication prescribing data.
Four mutually exclusive cohorts were defined by background therapy (GLP-1 receptor agonist or SGLT2 inhibitor) and 90-day add-on status, supporting four prespecified pairwise comparisons of early complementary add-on against monotherapy or against usual-care add-on (DPP-4 inhibitor, sulfonylurea, or insulin).
Descrizione
Inclusion Criteria:
- Adults aged 18 years or older.
- BMI ≥27 kg/m², or diagnosis codes consistent with obesity
- Type 2 diabetes mellitus
- Cardiovascular-kidney-metabolic syndrome stage 2-3
- Metabolic dysfunction-associated steatotic liver disease
- New initiation of GLP-1 receptor agonist therapy or SGLT2 inhibitor therapy during the study period as background therapy
- No prescription of either GLP-1 receptor agonist or SGLT2 inhibitor within the 6-month washout window before background therapy initiation
Exclusion Criteria:
- Type 1 diabetes mellitus, or other specified diabetes types that are not type 2 diabetes
- Human immunodeficiency virus infection
- Other chronic, alcohol-related, or secondary liver diseases
- Prior bariatric surgery
- Prior solid-organ transplantation
- Hepatocellular carcinoma or liver transplant within 1 year before background therapy initiation
- Major cardiovascular, kidney, or liver event within the 6-month window before background therapy initiation
- Transplant-related complications
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
Coorti e interventi
Gruppo / Coorte |
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GLP-1 RA with SGLT2i Add-On
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated GLP-1 receptor agonist therapy and added an SGLT2 inhibitor within 90 days after treatment initiation.
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GLP-1 RA monotherapy
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated GLP-1 receptor agonist therapy and did not receive early add-on therapy with an SGLT2 inhibitor within 90 days after treatment initiation.
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SGLT2i with GLP-1 RA Add-On
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated SGLT2 inhibitor therapy and added a GLP-1 receptor agonist within 90 days after treatment initiation.
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SGLT2i monotherapy
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated SGLT2 inhibitor therapy and did not receive early add-on therapy with a GLP-1 receptor agonist within 90 days after treatment initiation.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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All-cause Mortality (Comparison 1)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated GLP-1 RA therapy with early SGLT2i add-on versus those who initiated GLP-1 RA therapy without early SGLT2i add-on (monotherapy).
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From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause Mortality (Comparison 2)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated GLP-1 RA therapy with early SGLT2i add-on versus those who initiated GLP-1 RA therapy with usual care (DPP-4 inhibitor, sulfonylurea, or insulin add-on).
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From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause Mortality (Comparison 3)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated SGLT2i therapy with early GLP-1 RA add-on versus those who initiated SGLT2i therapy without early GLP-1 RA add-on (monotherapy).
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From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause Mortality (Comparison 4)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated SGLT2i therapy with early GLP-1 RA add-on versus those who initiated SGLT2i therapy with usual care (DPP-4 inhibitor, sulfonylurea, or insulin add-on).
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From 90 days after treatment initiation through up to 60 months of follow-up
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Major Adverse Cardiovascular Events (Comparison 1)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA monotherapy.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Cardiovascular Events (Comparison 2)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA with usual care.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Cardiovascular Events (Comparison 3)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i monotherapy.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Cardiovascular Events (Comparison 4)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i with usual care.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Kidney Events (Comparison 1)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA monotherapy.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Kidney Events (Comparison 2)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA with usual care.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Kidney Events (Comparison 3)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i monotherapy.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Kidney Events (Comparison 4)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i with usual care.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Liver Outcomes (Comparison 1)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatic failure, hepatorenal syndrome), hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA monotherapy.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Liver Outcomes (Comparison 2)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of hepatic decompensation, hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA with usual care.
|
From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Liver Outcomes (Comparison 3)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of hepatic decompensation, hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i monotherapy.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Major Adverse Liver Outcomes (Comparison 4)
Lasso di tempo: From 90 days after treatment initiation through up to 60 months of follow-up
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Composite of hepatic decompensation, hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i with usual care.
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From 90 days after treatment initiation through up to 60 months of follow-up
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
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- 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.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
1 gennaio 2017
Completamento primario (Effettivo)
31 marzo 2026
Completamento dello studio (Effettivo)
31 marzo 2026
Date di iscrizione allo studio
Primo inviato
26 aprile 2026
Primo inviato che soddisfa i criteri di controllo qualità
29 aprile 2026
Primo Inserito (Effettivo)
5 maggio 2026
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
25 giugno 2026
Ultimo aggiornamento inviato che soddisfa i criteri QC
28 maggio 2026
Ultimo verificato
1 maggio 2026
Maggiori informazioni
Termini relativi a questo studio
Altri numeri di identificazione dello studio
- CS1-26035
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
NO
Descrizione del piano IPD
Individual participant data will not be shared.
This retrospective observational study uses de-identified electronic health record data from the TriNetX US Collaborative Network.
Access to individual-level data is restricted by data use agreements, institutional policies, and privacy protections.
Researchers who meet eligibility requirements may obtain access to similar de-identified data through a TriNetX license or through participating institutions.
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
No
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .