Weight Changes After Incretin-mimetics

The goal of this study is to identify people at risk of weight regain after stopping an injectable weight loss drug. The main question the investigators aim to answer is: Can weight regain be predicted by measuring circulating Agouti-related peptide, a small protein coming from the brain?

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity and Obesity-related Medical Conditions
• Intervention / Treatment: Other: discontinuation of weight loss medication

Detailed Description

This study will enroll people who are taking an injectable weight loss drug, have lost weight with the help of this drug, and are required by their health insurance plan to discontinue treatment. Participants will first be screened for health conditions that would prevent them from entering the study. Once enrolled, participants will be asked to have the following testing while still on the injectable weight loss drug: body weight measurement, body composition (fat and lean mass), resting energy expenditure (calories burned), multiple blood draws after overnight fast and after drinking and nutritional shake urine collection, urine collection, measurement of heart rate, measurement of physical activity and sleep, questionnaires. Participants will then stop taking the injectable weight loss drug when the prescription runs out, and the same tests will be repeated 3 months later.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lisa L Morselli, MD PhD; Phone Number: 414-955-6710; Email: lmorselli@mcw.edu
• Study Contact Backup: Name: Roland James; Phone Number: 414-955-4992 414-955-6710; Email: rjames@mcw.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• adults 18 years or older
• men and women
• prescribed an incretin-mimetic for weight loss and for whom insurance coverage for this specific drug will lapse
• any ethnicity

Exclusion Criteria:

• weight > or = 400 lb
• type 1 or type 2 diabetes
• patients taking steroid medications
• anemia
• heart disease
• advanced kidney disease (CKD stage 4 and 5)
• decompensated liver disease
• hyperthyroidism
• untreated hypothyroidism
• active cancer
• post solid organ or bone marrow transplant
• HIV/AIDS
• pregnancy/plan for pregnancy in the next 6 months
• breastfeeding
• post-menopausal women
• current smoker
• current recreational drug use
• night shift or rotating shift workers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: incretin mimetic discontinuation; This study will enroll people who are taking an injectable weight loss drug, have lost weight with the help of this drug, and are required by their health insurance plan to discontinue treatment. They will be studied right before their medication runs out, and 3 months later	Other: discontinuation of weight loss medication; Participants will be studied right before their injectable weight loss medication runs out, and 3 months later

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
weight change	weight trajectories in the 3 months after treatment discontinuation	3 months
fasting and post-prandial circulating AgRP	Circulating AgRP will be measured after an overnight fast and during a 3-hour mixed meal test, at baseline (while still on injectable weight loss drug) and 3 months later. The mixed meal will consist in a nutrtional shake consumed in 5 min.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
resting metabolic rate (RMR)	RMR will be measured in fasting conditions at baseline (while still on injectable weight loss drug) and 3 months after treatment discontinuation.	3 months
RMR adaptation	RMR adaptation will be estimated baseline (while still on injectable weight loss drug) and 3 months after treatment discontinuation. RMR adaptation will be defined as the difference between measured and predicted RMR. Predicted RMR will be computed with a linear regression equation obtained from baseline data from the whole cohort.	3 months
body composition	Body composition (fat mass, fat-free mass) will be measured at baseline and 3 months later by DXA	3 months
subjective hunger ratings	Participants will be asked to rate current hunger with a visual analogue scale in fasting conditions and hourly during a 3-hour mixed meal test. This will be done at baseline (while still on injectable weight loss drug) and 3 months after treatment discontinuation. Scores go from 0 to 100, with 0 indicating "Not hungry at all" and 100 indicating "Extremely hungry".	3 months

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Collaborators: University of Wisconsin, Milwaukee

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): November 30, 2031
• Study Completion (Estimated): November 30, 2031

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 28, 2025

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: obesity; weight loss; weight gain
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Weight Gain
• Other Study ID Numbers: PRO00052666

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All datasets that pass quality control procedures and any other data that are deemed necessary to validate and replicate research findings will be shared.
• IPD Sharing Time Frame: The data deposited will be made available to all investigators in the research community as soon as possible but no later than 12 months from the completion of the funding period or upon acceptance of the data for publication and release from journals, whichever is earlier. Requests for data will be filled in a timely manner, usually within 2 to 6 weeks of the request, depending on the chronological position of the request within the queue. In addition, research data which documents, supports, or validates the published research findings, will be made available (electronically or mailed hard-copies) upon request to NIH-funded research programs. The duration of preservation and sharing of the data will be a minimum of 10 years after the funding period.
• IPD Sharing Access Criteria: Other researchers will be able to access the IPD if they submit a proposal that describes planned analyses. A data sharing agreement must be signed. Researchers interested in the IPD can contact Dr. Morselli by email and send documents by email. Dr. Morselli will then share the ICR.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

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