Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM)- Semaglutide v DPP4 Inhibitors

This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: Semaglutide; Drug: DPP-4 inhibitor

Detailed Description

This is a non-randomized, non-interventional study that is part of the DREAM Study of Brigham and Women's Hospital. DREAM is led by Dr. Madhav Thambisetty, MD, PhD, Chief of the Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA) intramural research program. This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication using healthcare claims data.

• Study Type: Observational
• Enrollment (Actual): 742670

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will employ a new user, active comparator, observational cohort study design comparing semaglutide v DPP4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin). The patients will be required to have continuous enrollment during the baseline period of 365 days before initiation of study drugs (index date). Follow-up for the outcome (dementia) differs between analyses. Follow-up begins the day after drug initiation (analysis 1, 3, 4); 180 days after drug initiation (analysis 2).

Description

Please see https://drive.google.com/drive/folders/1VRjPaaelXFyBbA5gV6pwB_ijSIMyIJ4N?usp=share_link or Appendix A(https://drive.google.com/drive/folders/1OgKQlxsJi9UWRDd3Kbaux_8adngoSnZY?usp=sharing) for full code and algorithm definitions.

Medicare timeframe: 2008 to 2019 (end of data availability).

Inclusion Criteria:

• 1. Aged >/= 65 years on the index date
• 2. Enrollment in Medicare Part A, B, and D with no HMO coverage for 365 days prior to and including cohort entry date
• 3. Diagnosis code for type 2 diabetes measured 365 days prior to drug initiation

Exclusion Criteria:

• 1. Prior history of dementia measured anytime prior to cohort entry date
• 2. Prior history of nursing home admission in the 365 days prior to the cohort entry date
• 3. Prior use of any GLP receptor agonists (semaglutide, exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide) or DPP4 inhibitors
• 4. Prior use of Semaglutide or DPP4 inhibitors concomitantly on index date

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Semaglutide; Exposure group	Drug: Semaglutide; Semaglutide claim is used as the exposure group.
DPP4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin); Reference group	Drug: DPP-4 inhibitor; DPP4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) claim is used as the reference group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Dementia Onset	Time to dementia onset, i.e., Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition due to size limitations.	Median follow up times: 1) 98 days (exp), 134 days (ref) 2) 118 days (exp), 132 days (ref) 3) 90 days (exp), 308 days (ref) 4) 99 days (exp), 135 days (ref)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Alzheimer's disease onset	Time to Alzheimer's disease onset. Please refer to uploaded protocol for full definition due to size limitations.	From date of drug initiation until the first of Alzheimer's disease onset, end of Medicare enrollment, or end of study period, whichever came first, assessed up to 6 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Johns Hopkins University; National Institute on Aging (NIA); Rutgers University
• Investigators: Principal Investigator: Madhav Thambisetty, MD, PhD, National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Protease Inhibitors; Enzyme Inhibitors; Pharmacologic Actions; Chemical Actions and Uses; Dipeptidyl-Peptidase IV Inhibitors; semaglutide
• Other Study ID Numbers: 2019P003607-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No