ObesityTiTRENCT07574723
Tirzepatide Titration to Reduce Side Effects in Individuals With Obesity
A study testing Tirzepatide (Per-label titration) and Tirzepatide (Flexible titration) in people with Obesity, run by Dasman Diabetes Institute at 1 site in Kuwait.
Trial summary
The goal of this clinical trial is to determine whether a flexible, symptom-guided titration strategy for tirzepatide can help adults with obesity without diabetes stay on treatment longer, while maintaining weight-loss effectiveness. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Obesity
- What is being tested?
- Tirzepatide (Per-label titration) and Tirzepatide (Flexible titration)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteKuwait
- Study dates
- 15 May 2026to 31 Dec 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 1. 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.
- Current use, or use within 90 days before screening, of medications with the potential to increase body weight (e.g., systemic glucocorticosteroids, antipsychotics, antidepressants, and antiepileptics) or to reduce body weight (e.g., diuretics).
- 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.
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- 3. 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.
- Renal impairment measured as estimated glomerular filtration rate value of <15 mL/min/1.73 m2 as defined by KDIGO 2012 by the central laboratory at screening.
- History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack within the past 60 days prior to screening.
- Subject presently classified as being in New York Heart Association Class IV.
- Surgery scheduled for the duration of the trial, except for minor surgical procedures, in the opinion of the investigator.
- Known or suspected abuse of alcohol or recreational drugs.
- Known or suspected hypersensitivity to trial product(s) or related products.
- Previous participation in this trial. Participation is defined as signed informed consent.
- Participation in another clinical trial within 90 days before screening.
- Female who is pregnant, breast-feeding, or intends to become pregnant, or is of child-bearing potential and not using a highly effective contraceptive method.
- Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Kuwait1 site, 1 recruiting
- Recruiting
Dasman Diabetes Institute
Kuwait City, 15462
Ebaa S AlOZairi, MD, 22242999 ext. 3111, ebaa.alozairi@dasmaninstitute.org
Ebaa AlOzairi
About this study
Official title: Tirzepatide Titration to Reduce Side Effects (TiTRE) in Individuals With Obesity
The goal of this clinical trial is to determine whether a flexible, symptom-guided titration strategy for tirzepatide can help adults with obesity without diabetes stay on treatment longer, while maintaining weight-loss effectiveness. The main questions it aims to answer are:
- Does flexible, symptom-guided titration increase time on treatment (delay treatment discontinuation) compared with standard per-label titration over 76 weeks?
- Does flexible titration reduce gastrointestinal side effects, such as nausea and vomiting, compared with standard titration?
- Does flexible titration achieve weight loss comparable to standard titration?
Read more
Researchers will compare standard per-label titration with a click-based, symptom-guided titration approach to assess differences in treatment persistence, tolerability, and effectiveness.
Participants will:
- 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, treatment persistence, and long-term treatment outcomes.
Read the detailed description
Tirzepatide is an effective treatment for obesity, but gastrointestinal adverse events during dose escalation may limit tolerability and lead to early treatment discontinuation. Current labeling recommends a fixed titration schedule that does not account for individual differences in symptom tolerance. Evidence supporting individualized titration strategies in obesity treatment remains limited.
This randomized clinical trial aims to evaluate whether a flexible, symptom-guided titration strategy for tirzepatide can prolong time on treatment while maintaining weight-loss effectiveness in adults with obesity without diabetes. Participants will be randomly assigned to either standard per-label titration or a flexible, click-based titration approach that allows smaller dose increments based on individual tolerability.
Participants in the standard group will follow the approved fixed dose-escalation schedule, while participants in the flexible group will advance doses according to gastrointestinal symptom severity, with the goal of minimizing nausea and vomiting. All participants will attend study visits over 76 weeks for assessment of treatment persistence, weight change, gastrointestinal tolerability, safety, and adherence.
The primary outcome is time to discontinuation of the treatment regimen over 76 weeks, analyzed as restricted mean time on treatment. Secondary outcomes include the incidence of gastrointestinal adverse events (including nausea and vomiting) and weight change. Participants currently using, or who have used within 90 days before screening, medications that may increase or reduce body weight will be excluded.
This study aims to inform individualized dosing approaches that may improve treatment persistence and long-term obesity treatment outcomes.
- Conditions
- Obesity
- Being tested
- Tirzepatide (Per-label titration), Tirzepatide (Flexible titration)
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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.
| Study group | Role | What they receive |
|---|---|---|
| Per-label arm (Control) | Active comparator | Participants receive tirzepatide with dose escalation according to the manufacturer's prescribing information. Receives: Drug: Tirzepatide (Per-label titration) |
| Flexible titration arm (Intervention) | Experimental | Participants receive tirzepatide administered with a flexible dose escalation schedule. Receives: Drug: Tirzepatide (Flexible titration) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to discontinuation of the treatment regimen
Time from randomization to permanent discontinuation of the assigned tirzepatide titration regimen due to adverse events. Analyzed as restricted mean time on treatment (RMST), estimated as the area under the Kaplan-Meier curve up to 76 weeks and reported in weeks. Participants remaining on treatment at Week 76 are censored at that time. Higher values indicate longer time on treatment (better outcome).
Measured: Randomization to Week 76
Secondary outcomes (34)
Exposure-adjusted rate of vomiting episodes assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)
Vomiting is assessed weekly using the validated M-INVR. The vomiting component is scored from 0 (no vomiting) to 4 (severe or frequent vomiting), with higher scores indicating worse outcomes. Vomiting burden will be summarized as weekly vomiting severity scores and as an exposure-adjusted rate (episodes per patient-week), calculated as the total number of vomiting episodes divided by each participant's total follow-up time
Measured: Baseline to Week 76
Incidence, frequency, and duration of vomiting assessed using the MASCC Antiemesis Tool - Modified Index of Nausea and Vomiting (M-INVR)
Vomiting is assessed weekly using the MASCC Antiemesis Tool - Modified Index of Nausea and Vomiting (M-INVR), a validated patient-reported outcome measure.
The vomiting subscale score is calculated as the sum of relevant vomiting items, with scores ranging from 0 to 16, where higher scores indicate greater incidence, frequency, and duration of vomiting (worse outcome).
Measured: Baseline to Week 76
Change in body weight
Absolute and percentage change in body weight from baseline.
Measured: Baseline to Week 76
Proportion of participants remaining on active study medication
Number of participants continuing to receive active study medication at the end of the trial.
Measured: Week 76
Change in glycated hemoglobin (HbA1c)
Change in HbA1c from baseline.
Measured: Baseline to Week 76
Change in lean body mass assessed by dual-energy X-ray absorptiometry (DEXA)
Change in total lean body mass measured by dual-energy X-ray absorptiometry (DEXA).
Measured: Baseline to Week 76
Change in visceral adiposity assessed by dual-energy X-ray absorptiometry (DEXA)
Change in visceral adipose tissue measured by dual-energy X-ray absorptiometry (DEXA).
Measured: Baseline to Week 76
Change in fat body mass assessed by dual-energy X-ray absorptiometry (DEXA)
Change in total fat body mass measured by dual-energy X-ray absorptiometry (DEXA).
Measured: Baseline to Week 76
Change in Alanine Aminotransferase (ALT)
Change from baseline in serum alanine aminotransferase (ALT) levels in U/L, measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in Aspartate Aminotransferase (AST)
Change from baseline in serum aspartate aminotransferase (AST) levels in U/L, measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in Gamma-Glutamyl Transferase (GGT)
Change from baseline in serum gamma-glutamyl transferase (GGT) levels in U/L, measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in Alkaline Phosphatase (ALP)
Change from baseline in serum alkaline phosphatase (ALP) levels in U/L, measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in Fibrosis-4 (FIB-4) index
Change from baseline in the Fibrosis-4 (FIB-4) index, a composite score calculated as:
FIB-4 = (Age × AST) / (Platelet count × √ALT), where age is measured in years, AST and ALT in U/L, and platelet count in 10⁹/L. The FIB-4 index is reported as a unitless value, with higher values indicating greater liver fibrosis. Values typically range from approximately 0 to 10.
Measured: Baseline to Week 76
Change in Total Cholesterol
Change from baseline in fasting total cholesterol levels measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in Low-Density Lipoprotein Cholesterol (LDL-C)
Change from baseline in fasting low-density lipoprotein cholesterol (LDL-C) levels measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in High-Density Lipoprotein Cholesterol (HDL-C)
Change from baseline in fasting high-density lipoprotein cholesterol (HDL-C) levels measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in Triglycerides
Change from baseline in fasting triglyceride levels measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in estimated glomerular filtration rate (eGFR)
Change from baseline in estimated glomerular filtration rate (eGFR) calculated using a standard equation.
Measured: Baseline to Week 76
Change in serum creatinine
Change from baseline in serum creatinine measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in urinary microalbumin
Change from baseline in urinary microalbumin concentration measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in urine albumin-to-creatinine ratio (ACR)
Change from baseline in urine albumin-to-creatinine ratio (ACR) measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in thyroid-stimulating hormone (TSH)
Change from baseline in serum thyroid-stimulating hormone (TSH) measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in free thyroxine (free T4)
Change from baseline in serum free thyroxine (free T4) measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in interleukin-6 (IL-6)
Change from baseline in circulating interleukin-6 (IL-6) concentration measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in interleukin-10 (IL-10)
Change from baseline in circulating interleukin-10 (IL-10) concentration measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in interleukin-1 receptor antagonist (IL-1Ra)
Change from baseline in circulating interleukin-1 receptor antagonist (IL-1Ra) concentration measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in tumor necrosis factor-alpha (TNF-α)
Change from baseline in circulating tumor necrosis factor-alpha (TNF-α) concentration measured using standard laboratory methods.
Measured: Baseline to Week 76
Change in health-related quality of life assessed using the 36-Item Short Form Health Survey (SF-36)
Health-related quality of life is assessed using the 36-Item Short Form Health Survey (SF-36), a validated patient-reported outcome measure.
The SF-36 yields an overall score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Measured: Baseline to Week 76
Change in dietary intake patterns
Changes in macronutrient composition and total caloric intake assessed using multiple-pass 24-hour dietary recalls.
Measured: Baseline to Week 76
Incidence of adverse events and laboratory abnormalities
Incidence of treatment-emergent adverse events and clinically significant laboratory abnormalities.
Measured: Baseline to Week 76
Change in retinal nerve fiber layer thickness assessed by optical coherence tomography (OCT)
Change from baseline in retinal nerve fiber layer thickness measured by optical coherence tomography
Measured: Baseline to Week 76
Change in arterial stiffness measured by pulse wave velocity (PWV)
Change from baseline in arterial stiffness assessed by carotid-femoral pulse wave velocity.
Measured: Baseline to Week 76
Change in sudomotor function assessed by Sudoscan
Change from baseline in sudomotor function measured by electrochemical skin conductance using Sudoscan.
Measured: Baseline to Week 76
Treatment Persistence and Discontinuation
Treatment persistence will be assessed by the proportion of participants remaining on active study medication at week 76. Treatment discontinuation and reasons for discontinuation will be recorded throughout the study and categorized as gastrointestinal adverse events (including nausea and vomiting), other adverse events, lack of efficacy, participant preference, protocol non-adherence, loss to follow-up, pregnancy, investigator decision, or other specified reasons.
Measured: Up to 76 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2026
- Study start15 May 2026
- Primary completion15 May 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This 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
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dasman Diabetes Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ulster
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07574723
- Sponsor's protocol ID
- RA HM-2026-06
- Acronym
- TiTRE
- Status last verified
- Jul 2026
- First submitted
- 19 Apr 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No