Tirzepatide Titration to Reduce Side Effects in Individuals With Obesity

NCT07574723 | Not Yet Recruiting

• 1 other identifier: RA HM-2026-06
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to determine whether a flexible, symptom-guided titration strategy for tirzepatide can reduce gastrointestinal side effects while maintaining weight-loss effectiveness in adults with obesity without diabetes. The main questions it aims to answer are:

• Be randomly assigned to standard or flexible tirzepatide titration
• Use a click-based dosing method that allows small dose increases based on tolerability (flexible group)
• Attend study visits over 76 weeks for safety and outcome assessments This study addresses the lack of evidence for individualized titration strategies in obesity treatment and aims to improve tolerability, adherence, and long-term treatment outcomes.

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• Number of vomiting episodes per patient assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)

  The vomiting component of the Modified Index of Nausea, Vomiting, and Retching (M-INVR) is administered weekly. Scores range from 0 (no vomiting) to 4 (severe or frequent vomiting), with higher scores indicating worse vomiting outcomes.

  From enrollment (at baseline) to the end of treatment at 76 weeks.

Secondary Outcomes (32)

• Incidence, frequency, and duration of vomiting assessed using the MASCC Antiemesis Tool - Modified Index of Nausea and Vomiting (M-INVR)

  Baseline to Week 76

• Change in body weight

  Baseline to Week 76

• Proportion of participants remaining on active study medication

  Week 76

• Change in glycated hemoglobin (HbA1c)

  Baseline to Week 76

• Change in lean body mass assessed by dual-energy X-ray absorptiometry (DEXA)

  Baseline to Week 76

Study Arms (2)

Per-label arm (Control)

ACTIVE COMPARATOR

Participants receive tirzepatide with dose escalation according to the manufacturer's prescribing information.

Drug: Tirzepatide (Per-label titration)

Flexible titration arm (Intervention)

EXPERIMENTAL

Participants receive tirzepatide administered with a flexible dose escalation schedule.

Drug: Tirzepatide (Flexible titration)

Interventions

Tirzepatide (Per-label titration) DRUG

Tirzepatide is administered by subcutaneous injection once weekly. Dose escalation follows the manufacturer's prescribing information, with advancement through labeled dose levels at prespecified intervals to the assigned maintenance dose

Per-label arm (Control)

Tirzepatide (Flexible titration) DRUG

Tirzepatide is administered by subcutaneous injection once weekly. Dose escalation follows a flexible titration schedule as defined in the study protocol.

Flexible titration arm (Intervention)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 years and older
• A diagnosis of obesity (BMI ≥ 27 kg/m2) at screening with self-reported unsuccessful dietary efforts to lose weight.
• No diagnosis of diabetes mellites.
• Able to understand and sign the consent form
• Able to undergo DEXA scan.

You may not qualify if:

• \. History of type 1 or type 2 diabetes mellites. 2. Obesity-related:
• A self-reported change in body weight \>5 kg (11 lbs) within 90 days before screening irrespective of medical records.
• Treatment with any medication for the indication of obesity within the past 90 days before screening.
• Previous or planned (during the trial period) obesity treatment with surgery or a weight-loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed \>1 year before screening; (2) lap banding, if the band has been removed \>1 year before screening; (3) intragastric balloon, if the balloon has been removed \>1 year before screening; or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed \>1 year before screening.
• Uncontrolled thyroid disease, defined as thyroid stimulating hormone \>6.0 mIU/L or \<0.4 mIU/L as measured by the central laboratory at screening.
• \. Mental health:
• History of major depressive disorder within 2 years before screening.
• Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder).
• A Patient Health Questionnaire-9 score of ≥15 at screening.
• A lifetime history of a suicidal attempt.
• Suicidal behavior within 30 days before screening. 4. General safety:
• Use of non-herbal Chinese medicine or other non-herbal local medicine with unknown/unspecified content within 90 days before screening.
• Presence of acute pancreatitis within the past 180 days prior to the day of screening.
• History or presence of chronic pancreatitis.
• Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.

Sponsors & Collaborators

• Dasman Diabetes Institute: lead
• University of Ulster: collaborator

MeSH Terms

Conditions

Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Blinding will be maintained for outcome assessors and data analysts to minimize bias. While participants cannot be blinded to treatment allocation due to the nature of the intervention, all personnel involved in outcome measurement and statistical analysis will remain unaware of group assignments. Procedures for maintaining blinding will include secure allocation concealment and restricted access to randomization codes.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The is an open-label, two-arm, parallel, randomized controlled trial over 76 weeks, enrolling individuals with obesity (BMI ≥ 27 kg/m2) and without diabetes, with participants randomized to either a per-label arm or a flexible titration arm

Study Record Dates

• First Submitted: April 19, 2026
• First Posted: May 8, 2026
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 15, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share