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

Launched by MAYO CLINIC · Jan 24, 2025

Keywords

ClinConnect Summary

This clinical trial is studying the effects of two medications, semaglutide and tirzepatide, on how food moves through the stomach in people with obesity. The researchers want to understand how these medications compare to a placebo (a treatment with no active ingredients) over 24 weeks. Participants will receive weekly injections of either semaglutide, tirzepatide, or a placebo, and their gastric function will be measured at different times during and after the treatment.

To be eligible for this trial, participants must be adults between the ages of 18 and 75 with a body mass index (BMI) over 30, or over 27 if they also have prediabetes or type 2 diabetes managed by diet alone. They should live within 50 miles of the Mayo Clinic and not be on certain medications that could interfere with the study. Participants can expect to attend several visits over the study period, where their stomach function will be assessed to see how well they respond to the treatments. It's important to note that individuals with certain health conditions or those taking specific medications may not be eligible for participation.

Gender

ALL

Eligibility criteria

• 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