Tirzepatide vs Semaglutide in Individuals at Cardiovascular Risk But Without Diabetes.
8 juillet 2026 mis à jour par: Shirley Vichy Wang, Brigham and Women's Hospital
Comparative Effectiveness of Tirzepatide and Semaglutide in Patients at Cardiovascular Risk With Overweight or Obesity But Without Diabetes
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials.
The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to assess the comparative effectiveness of tirzepatide vs semaglutide on cardiovascular outcomes among patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
The SELECT trial (NCT03574597) demonstrated that semaglutide reduces major adverse cardiovascular events in individuals with established cardiovascular disease and overweight or obesity but without diabetes. Whether tirzepatide provides similar cardiovascular benefit in patients without diabetes is being evaluated in the ongoing placebo-controlled SURMOUNT-MMO trial (NCT05556512), with results expected in late 2027. Although SURMOUNT-MMO will assess the cardiovascular efficacy of tirzepatide in individuals without diabetes, evidence to inform treatment choices among available incretin-based therapies in clinical practice is urgently needed. Therefore, this study examines the comparative effectiveness of tirzepatide vs semaglutide among patients at cardiovascular risk with overweight or obesity but without diabetes in clinical practice.
Although many features of the target trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice.
The database study will be a new-user active-comparative study, conducted using 3 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality, myocardial infarction, or stroke. Clinical guidelines during the study period recommended both tirzepatide and semaglutide for the same indications of glucose lowering and weight reduction.
Type d'étude
Observationnel
Inscription (Réel)
100000
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
-
-
Massachusetts
-
Boston, Massachusetts, États-Unis, 02120
- Brigham and Women's Hospital
-
-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Non
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
Individuals aged 18 years or older at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice
La description
Study period:
Optum: Eligible cohort entry period between May 13, 2022 to November 30, 2025. MarketScan: Eligible cohort entry period between May 13, 2022 to September 30, 2023.
Medicare: Eligible cohort entry period between May 13, 2022 to September 30, 2024.
Inclusion Criteria:
- Men or women aged 18 years or older
- History of myocardial infarction, stroke, any surgical or percutaneous revascularization procedure
- Use of antihypertensive or lipid-lowering drugs
- Coronary, carotid, or peripheral artery disease
- BMI greater than or equal to 25.0 mg/m2
Exclusion Criteria:
- Medullary thyroid carcinoma
- MEN syndrome type 2
- Malignancy
- Type 1 diabetes
- Type 2 diabetes
- Secondary diabetes
- End-stage renal disease or dialysis
- Pregnancy
- History of bariatric surgery
- Prior use of pramlintide or any GLP-1-RA, except tirzepatide or semaglutide
- Cardiovascular event or intervention in the last 7 days
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
Tirzépatide
Groupe d'exposition
|
Initiation of tirzepatide described in electronic health records is used as the exposure.
|
|
Injectable semaglutide
Reference group
|
Initiation of injectable semaglutide described in electronic health records is used as the reference.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Composite of all-cause mortality, myocardial infarction, or stroke.
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the individual components of the primary endpoint, i.e., death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Hospitalization for heart failure
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the occurrence of heart failure hospitalizations in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Hospitalization for unstable angina
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the occurrence of hospitalizations for unstable angina in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Coronary revascularization
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the occurrence of coronary revascularization in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Urinary tract infections
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the safety outcome of urinary tract infections in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Serious infections
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the safety outcome of serious infections in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Gastrointestinal adverse events
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the safety outcome of gastrointestinal adverse events in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Hernia
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the negative control outcome of hernia in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
|
Lumbar radiculopathy
Délai: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the negative control outcome of lumbar radiculopathy in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
|
1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Shirley Wang, PhD, ScM, Brigham and Women's Hospital
- Chercheur principal: Nils Krüger, MD, Brigham and Women's Hospital
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
10 février 2026
Achèvement primaire (Réel)
1 juin 2026
Achèvement de l'étude (Réel)
1 juin 2026
Dates d'inscription aux études
Première soumission
23 mai 2026
Première soumission répondant aux critères de contrôle qualité
23 mai 2026
Première publication (Réel)
2 juin 2026
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
9 juillet 2026
Dernière mise à jour soumise répondant aux critères de contrôle qualité
8 juillet 2026
Dernière vérification
1 mai 2026
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Troubles nutritionnels
- Suralimentation
- Poids
- Conditions pathologiques, signes et symptômes
- Maladies nutritionnelles et métaboliques
- Signes et symptômes
- En surpoids
- Obésité
- Acides aminés, peptides et protéines
- Protéines
- Récepteur du peptide-1 de type glucagon
- Récepteurs peptidiques de type glucagon
- Récepteurs, G-protéines G
- Récepteurs, surface cellulaire
- Protéines membranaires
- Récepteurs, hormones gastro-intestinales
- Récepteurs, peptide
- Tirzépatide
- sémaglutide
Autres numéros d'identification d'étude
- 2018P002966-TIRZSEMA-MMO
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
produit fabriqué et exporté des États-Unis.
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .