ClinicalTrials.gg
RecruitingNCT07574723TiTREUpdated Oct 20, 2026

Tirzepatide Titration to Reduce Side Effects in Individuals With Obesity

An interventional study of Tirzepatide (Per-label titration) and Tirzepatide (Flexible titration) in Obesity, sponsored by Dasman Diabetes Institute. Recruiting at 1 site in Kuwait. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-10-20.

Sponsored by Dasman Diabetes Institute · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Started May 2026; still recruiting 5 months later.
Updated Oct 20, 2026Eligibility revisedPrimary outcomes revisedGo to Updates ↓
Phase
Not applicable
Study type
Interventional
Enrollment
68
Allocation
Randomized
Ages
18 Years to 100 Years
Sex
All
01

Study 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. 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?

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.

02

Conditions studied

  • Obesity

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03

In context

Obesity

11,522 studies on the registry are indexed under Obesity; 2,033 are open to participants now.

This study's planned enrollment of 68 is close to the median of 67 across 9,006 interventional studies indexed under Obesity.

Browse Obesity studies →

Lead sponsor

Dasman Diabetes Institute is the lead sponsor of 31 studies on the registry; 14 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

The criteria were revised on the registry on Oct 20, 2026. See what changed

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  • 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.

      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 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 within the past 60 days prior to screening.
    • Subject presently classified as being in 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 to trial product(s) or related products.
    • Previous participation in this trial. Participation is defined as signed .
    • Participation in another clinical trial within 90 days before screening.
    • Female who is pregnant, breast-feeding, or intends to become pregnant, or is of and not using a highly effective 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.
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
68 participants (estimated)

Study arms

  • Active comparator
    Per-label arm (Control)

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

    Drug: Tirzepatide (Per-label titration)

  • Experimental
    Flexible titration arm (Intervention)

    Participants receive tirzepatide administered with a flexible dose escalation schedule.

    Drug: Tirzepatide (Flexible titration)

Interventions

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

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Randomization to Week 76

Secondary outcomes

  1. 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

    Time frame: Baseline to Week 76

  2. 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).

    Time frame: Baseline to Week 76

  3. Change in body weight

    Absolute and percentage change in body weight from baseline.

    Time frame: Baseline to Week 76

  4. Proportion of participants remaining on active study medication

    Number of participants continuing to receive active study medication at the end of the trial.

    Time frame: Week 76

  5. Change in glycated hemoglobin (HbA1c)

    Change in HbA1c from baseline.

    Time frame: Baseline to Week 76

  6. 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).

    Time frame: Baseline to Week 76

  7. 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).

    Time frame: Baseline to Week 76

  8. 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).

    Time frame: Baseline to Week 76

  9. Change in Alanine Aminotransferase (ALT)

    Change from baseline in serum alanine aminotransferase (ALT) levels in U/L, measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  10. Change in Aspartate Aminotransferase (AST)

    Change from baseline in serum aspartate aminotransferase (AST) levels in U/L, measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  11. Change in Gamma-Glutamyl Transferase (GGT)

    Change from baseline in serum gamma-glutamyl transferase (GGT) levels in U/L, measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  12. Change in Alkaline Phosphatase (ALP)

    Change from baseline in serum alkaline phosphatase (ALP) levels in U/L, measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  13. 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.

    Time frame: Baseline to Week 76

  14. Change in Total Cholesterol

    Change from baseline in fasting total cholesterol levels measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  15. 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.

    Time frame: Baseline to Week 76

  16. 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.

    Time frame: Baseline to Week 76

  17. Change in Triglycerides

    Change from baseline in fasting triglyceride levels measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  18. Change in estimated glomerular filtration rate (eGFR)

    Change from baseline in estimated glomerular filtration rate (eGFR) calculated using a standard equation.

    Time frame: Baseline to Week 76

  19. Change in serum creatinine

    Change from baseline in serum creatinine measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  20. Change in urinary microalbumin

    Change from baseline in urinary microalbumin concentration measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  21. Change in urine albumin-to-creatinine ratio (ACR)

    Change from baseline in urine albumin-to-creatinine ratio (ACR) measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  22. Change in thyroid-stimulating hormone (TSH)

    Change from baseline in serum thyroid-stimulating hormone (TSH) measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  23. Change in free thyroxine (free T4)

    Change from baseline in serum free thyroxine (free T4) measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  24. Change in interleukin-6 (IL-6)

    Change from baseline in circulating interleukin-6 (IL-6) concentration measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  25. Change in interleukin-10 (IL-10)

    Change from baseline in circulating interleukin-10 (IL-10) concentration measured using standard laboratory methods.

    Time frame: Baseline to Week 76

  26. 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.

    Time frame: Baseline to Week 76

  27. 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.

    Time frame: Baseline to Week 76

  28. 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.

    Time frame: Baseline to Week 76

  29. Change in dietary intake patterns

    Changes in macronutrient composition and total caloric intake assessed using multiple-pass 24-hour dietary recalls.

    Time frame: Baseline to Week 76

  30. Incidence of adverse events and laboratory abnormalities

    Incidence of treatment-emergent adverse events and clinically significant laboratory abnormalities.

    Time frame: Baseline to Week 76

  31. 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

    Time frame: Baseline to Week 76

  32. Change in arterial stiffness measured by pulse wave velocity (PWV)

    Change from baseline in arterial stiffness assessed by carotid-femoral pulse wave velocity.

    Time frame: Baseline to Week 76

  33. Change in sudomotor function assessed by Sudoscan

    Change from baseline in sudomotor function measured by electrochemical skin conductance using Sudoscan.

    Time frame: Baseline to Week 76

  34. 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.

    Time frame: Up to 76 weeks

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

1 registry update since Sep 25, 2026
Eligibility
1 exclusion criterion added
What changed in the criteria
Exclusion criteria
  • AddedCurrent 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).
Oct 20, 2026
Primary outcomes
1 edited
What changed in the outcomes
  • ChangedBefore Vomiting episodes per patient assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)Now Time to discontinuation of the treatment regimenTime frame: From enrollment (at baseline) to the end of treatment at 76 weeks. → Randomization to Week 76
Oct 20, 2026
Secondary outcomes
1 added
What changed in the outcomes
  • AddedExposure-adjusted rate of vomiting episodes assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)Time frame: Baseline to Week 76
Oct 20, 2026
Show all 1 update
  1. Oct 20, 2026
    Eligibility 1 exclusion criterion added
    What changed in the criteria
    Exclusion criteria
    • AddedCurrent 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).
    Primary outcomes 1 edited
    What changed in the outcomes
    • ChangedBefore Vomiting episodes per patient assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)Now Time to discontinuation of the treatment regimenTime frame: From enrollment (at baseline) to the end of treatment at 76 weeks. → Randomization to Week 76
    Secondary outcomes 1 added
    What changed in the outcomes
    • AddedExposure-adjusted rate of vomiting episodes assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)Time frame: Baseline to Week 76
    + 2 other changes: description and design details

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07574723
Lead sponsor
Dasman Diabetes Institute
Collaborators
University of Ulster
Responsible party
Sponsor
First posted
May 8, 2026
Start date
May 15, 2026
Primary completion
May 15, 2029 (estimated)
Completion
Dec 31, 2029 (estimated)
Last update
Oct 20, 2026

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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