Injectable Semaglutide vs Dulaglutide in Individuals at Cardiovascular Risk

Comparative Effectiveness of Semaglutide and Dulaglutide in Patients at Low, Moderate, and High Cardiovascular Risk With Type 2 Diabetes and Overweight

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Overweight; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Semaglutide; Drug: Dulaglutide

Detailed Description

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 semaglutide vs dulaglutide on cardiovascular outcomes in individuals typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes (T2DM) and overweight.

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 semaglutide vs dulaglutide on the composite end point of all-cause mortality, myocardial infarction, or stroke. Clinical guidelines during the study period recommended both injectable semaglutide and dulaglutide for the same indications of glucose lowering and cardiovascular risk reduction.

• Study Type: Observational
• Enrollment (Estimated): 120000

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with T2DM and overweight.

Description

Study Period:

Optum: Eligible cohort entry period between December 5, 2017 to November 30, 2025.

MarketScan: Eligible cohort entry period between December 5, 2017 to September 30, 2023.

Medicare: Eligible cohort entry period between December 5, 2017 to September 30, 2020.

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
• Type 2 diabetes

Exclusion Criteria:

• Medullary thyroid carcinoma
• MEN syndrome type 2
• Malignancy
• Type 1 diabetes
• Secondary diabetes
• End-stage renal disease or dialysis
• Uncontrolled diabetic retinopathy or maculopathy
• Pregnancy
• History of bariatric surgery
• Prior use of pramlintide or any GLP-1-RA, except semaglutide or dulaglutide
• Cardiovascular event or intervention in the last 7 days

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dulaglutide; Reference group	Drug: Dulaglutide; Initiation of dulaglutide described in electronic health records is used as the reference.
Injectable semaglutide; Exposure group	Drug: Semaglutide; Initiation of injectable semaglutide described in electronic health records is used as the exposure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause mortality, myocardial infarction, or stroke.	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the composite of all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Hospitalization for heart failure	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the occurrence of heart failure hospitalizations in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Hospitalization for unstable angina	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on hospitalizations for unstable angina in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Coronary revascularization	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the occurrence of coronary revascularization in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary tract infections	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the safety outcome of urinary tract infections in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Serious infections	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the safety outcome of serious infections in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Gastrointestinal adverse events	To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the safety outcome of gastrointestinal adverse events in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Hernia	To evaluate the effect of injectable semaglutide vs dulaglutide on the negative control outcome of hernia in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA
Lumbar radiculopathy	To evaluate the effect of injectable semaglutide vs dulaglutide on the negative control outcome of lumbar radiculopathy in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight.	1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Shirley Wang, PhD, ScM, Brigham and Women's Hospital; Principal Investigator: Nils Krüger, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: May 23, 2026
• First Submitted That Met QC Criteria: May 23, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 23, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; semaglutide; dulaglutide
• Other Study ID Numbers: 2018P002966-SEMADULA-CVOT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No