Patient Selection Criteria for Retatrutide Research: How to Define Inclusion and Exclusion in Your IRB Protocol

One of the most important sections of any IRB research protocol is the patient selection criteria — the inclusion and exclusion criteria that define who is eligible to participate in your study. For retatrutide, these criteria serve two purposes: they define the patient population that is most likely to benefit from the compound, and they protect patients who are at elevated risk of harm. Getting this section right is both a clinical and a legal imperative.

The IRB will scrutinize your patient selection criteria carefully. Their job is to ensure that the research population is appropriate — that the potential benefits justify the risks for the specific patients you are enrolling, and that vulnerable populations are not being exposed to unnecessary risk.

From a legal standpoint, your inclusion and exclusion criteria define the boundaries of your research. If a patient who did not meet your inclusion criteria received the compound, or if a patient who met an exclusion criterion was enrolled anyway, that is a protocol deviation — and protocol deviations are exactly the kind of thing that creates liability exposure.

Based on the TRIUMPH trial population and the clinical rationale for retatrutide, reasonable inclusion criteria for a practice-based research protocol might include:

• Age: Adults 18 years or older (some protocols specify 18–75 to limit exposure in elderly populations with limited trial data)
• BMI: Typically ≥30 kg/m², or ≥27 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea)
• Clinical indication: Obesity or overweight with comorbidities, consistent with the TRIUMPH trial indication
• Capacity to consent: The patient must be able to understand and voluntarily provide informed consent
• Willingness to comply: The patient must be willing to comply with the study procedures, including follow-up visits and adverse event reporting

Exclusion criteria should reflect the known contraindications and risk factors identified in the TRIUMPH trial data and the general pharmacology of GLP/GIP/glucagon triple agonists:

• Personal or family history of medullary thyroid carcinoma (MTC): This is a standard exclusion for all GLP receptor agonists based on rodent carcinogenicity data
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2): Same rationale as MTC
• Active or recent pancreatitis: GLP receptor agonists have been associated with pancreatitis risk
• Severe renal impairment (eGFR <30 mL/min/1.73m²): Limited data in this population
• Severe hepatic impairment: Limited data in this population
• Pregnancy or breastfeeding: Investigational compounds should not be administered to pregnant or breastfeeding patients
• Active eating disorder: Anorexia nervosa or bulimia nervosa
• Recent cardiovascular event: Myocardial infarction or stroke within the past 90 days
• Current use of other GLP receptor agonists: To avoid pharmacodynamic interactions and confounding of research data
• Known hypersensitivity to any component of the formulation
• Inability to provide informed consent

For each patient enrolled in your study, your research record should document:

• How the patient was identified as a potential research subject
• Which inclusion criteria the patient meets and how that was determined
• Confirmation that no exclusion criteria apply, with documentation of how each was assessed
• The date and process of the consent discussion

This documentation demonstrates that your patient selection process was systematic and consistent — not arbitrary.

If a patient who does not meet your inclusion criteria requests enrollment, or if you discover after enrollment that a patient meets an exclusion criterion, that is a protocol deviation. Protocol deviations must be reported to the IRB. The IRB will determine whether the deviation requires a protocol modification, whether the patient should be withdrawn from the study, and whether any additional monitoring is required.

Do not try to manage protocol deviations quietly. The IRB oversight process exists precisely to handle these situations, and attempting to conceal a deviation creates far greater legal exposure than reporting it promptly.

Beyond the regulatory requirements, careful patient selection is simply good clinical practice. Retatrutide is a potent triple agonist with a meaningful side effect profile. Patients who are at elevated risk of adverse outcomes — because of comorbidities, contraindications, or other factors — deserve to have those risks carefully weighed before they are enrolled in a research study.

The patients most likely to benefit from retatrutide are those with significant obesity-related comorbidities who have not achieved adequate response to approved therapies. Focusing your research on this population is both clinically appropriate and the most defensible approach from a regulatory standpoint.