Effects of Long-Acting GLP-1 (Glucagon-like Peptide-1) or Dual Incretin (GLP-1 and GIP [Glucose-dependent Insulinotropic Peptide]) Modulation on Gastric Motor Functions

A Randomized, Placebo-Controlled Trial of the Effects of Long-Acting GLP-1 or Dual Incretin (GLP-1 and GIP) Modulation on Gastric Motor Functions

The purpose of this study is to compare effects of weekly SQ semaglutide 2.4mg SQ, SQ tirzepatide 10mg, and placebo administered for 24 weeks on GES measured repeatedly at baseline, 16 weeks, 24 weeks, 28 weeks, 4 weeks after stopping the medication, and accommodation and satiation at 24 weeks compared to baseline.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Semaglutide; Drug: Tirzepatide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

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

Description

PLEASE NOTE: Potential participants must reside within 50 miles of Mayo Clinic for 7 consecutive months due to non-mobile GI imaging cameras.

Inclusion criteria:

• Adults (18-75 years) who have BMI >30 or >27kg/m2 who also have prediabetes or T2DM on diet treatment only
• Able to reside within 50 miles of Mayo Clinic for the duration of the study
• Not currently on treatment (exceptions below) for cardiac, pulmonary, GI, hepatic, renal, hematological, neurological, or endocrine disorders.
• Biological sex: men or women. We shall attempt to recruit equal proportions of men and women. Women of childbearing potential will be using an effective form of contraception and have negative pregnancy tests within 48 hours of enrollment and before each isotope-based radiation exposure as part of the tests for gastric emptying. In addition, monthly urine pregnancy tests will be performed in females with childbearing potential.

Exclusion criteria:

• Weight exceeding 137kg (safety limit of camera for measuring gastric volumes)
• Abdominal surgery other than appendectomy, Caesarian section or tubal ligation, cholecystectomy
• Chronic GI diseases, systemic disease or medications that could affect GI motility, appetite or absorption
• Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia II
• Patients with T2DM on GLP-1RAs, amylin agonists/analogs (e.g. pramlintide), insulin, sulfonylureas (all due to risk of hypoglycemia with semaglutide or tirzepatide treatment); or on metformin, acarbose or DPP-4 inhibitors (e.g. sitagliptin and vildagliptin).
• Past or current history of pancreatitis, gallstones, history of alcoholism, blood triglyceride levels > 500mg/dL
• Significant untreated psychiatric dysfunction or an active eating disorder (Clark et al 2007, Cunningham et al 2012) based on screening with the Hospital Anxiety and Depression Inventory [HAD (Zigmond & Snaith 1983)], a self-administered alcoholism screening test [AUDIT-C (Bush et al 1998)], and the Questionnaire on Eating and Weight Patterns-Revised [binge eating disorders and bulimia (Yanovski et al 2015)]. If such a dysfunction is identified by a HAD score >11 on either the anxiety or depression subscales or difficulties with substance or eating disorders, the participant will be interviewed by a study investigator and, if excluded, will be given a referral letter to his/her primary care doctor for further appraisal and follow-up treatment.
• Intake of any medication (except multivitamins) within 7 days of the study. Exceptions are birth control pill, estrogen and thyroxine replacement, and medication administered for co-morbidities as long as they do not alter gastric functions. Thus, statins for hyperlipidemia, diuretics, β-adrenergic blockers, ACE inhibitors and angiotensin antagonists for hypertension are permissible. In contrast, resin sequestrants for hyperlipidemia (Psichas et al 2012), α2-adrenergic agonists for hypertension, are not permissible due to effects on stomach or appetite.
• Documented delayed gastric emptying: gastric emptying T1/2 >174 min or gastric retention at 4 hours >25% based on 5-95%ile of 319 controls' GES of the same meal (320kcal, 30% fat) (Camilleri et al 2012a, Table 1)
• Hypersensitivity to semaglutide or tirzepatide
• Participate in highly intense physical activity program that could potentially interfere with study interpretation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: semaglutide; Administered by subcutaneous injection once per week in accordance with FDA approved escalation as well as maintenance treatment	Drug: Semaglutide; Both interventions are approved by FDA for the treatment of obesity and are administered by subcutaneous injection once per week; Other Names: Tirzepatide
Experimental: Tirzepatide; Administered by subcutaneous injection once per week in accordance with FDA approved escalation as well as maintenance treatment	Drug: Tirzepatide; Both interventions are approved by FDA for the treatment of obesity and are administered by subcutaneous injection once per week
Placebo Comparator: placebo; Administered by subcutaneous injection once per week	Drug: Placebo; Placebo administered by subcutaneous injection once per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric emptying of solids T1/2 min, that is time for half meal to empty from stomach	Gastric emptying of an egg meal measured by scintigraphy	Measurement at baseline, after 16 and 24 weeks' treatment, and at 28 weeks (off treatment for 4 weeks)
Body weight	Measurement of body weight using weight scales	Measurement at baseline, after 16 and 24 weeks' treatment, and at 28 weeks (off treatment for 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calories to fullness, kilocalories (kcal)	Measurement of kilocalorie intake at comfortable fullness based on Ensure liquid nutrient	Measurement at baseline, and after 24 weeks' treatment
Maximum tolerated calories, kilocalories (kcal)	Measurement of kilocalorie intake at maximal fullness based on Ensure liquid nutrient	Measurement at baseline, and after 24 weeks' treatment
Fasting gastric volume, milliliters (mL)	Measurement of gastric volume during fasting using 99mTc-SPECT (single photon emission computed tomography) imaging	Measurement at baseline, and after 24 weeks' treatment
Gastric accommodation vol (postprandial minus fasting volume), milliliters (mL)	Measurement of gastric volume following 300 mL of Ensure using 99mTc-SPECT (single photon emission computed tomography) imaging	Measurement at baseline, and after 24 weeks' treatment
Peak postprandial GLP-1 (glucagon-like peptide-1) pmol/L	GLP-1 measured fasting, and 15, 45, and 90 minutes postprandially	Measurement at baseline, and after 24 weeks' treatment
Peak postprandial peptide tyrosine tyrosine (PYY) pmol/L	PYY measured fasting, and 15, 45, and 90 minutes postprandially	Measurement at baseline, and after 24 weeks' treatment
DEXA (dual energy X-ray absorptiometry) body composition	Body composition (including total body fat) by dual-energy X-ray absorptiometry (DEXA) technology	Measurement at baseline, and after 24 weeks' treatment

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael Camilleri, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: January 24, 2025
• First Posted (Actual): January 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide; semaglutide
• Other Study ID Numbers: 24-011786

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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