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

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