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Trial registered on ANZCTR


Registration number
ACTRN12625000841471
Ethics application status
Approved
Date submitted
30/06/2025
Date registered
5/08/2025
Date last updated
5/08/2025
Date data sharing statement initially provided
5/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Tirzepatide for the treatment of concurrent type 1 diabetes and overweight or obesity 2.0 - an open-label randomised crossover trial in adults
Scientific title
Tirzepatide for the treatment of concurrent type 1 diabetes and overweight or obesity 2.0 - an open-label randomised crossover trial in adults
Secondary ID [1] 314768 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TZP-T1D 2.0
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 337991 0
Obesity 337992 0
Overweight 337993 0
Condition category
Condition code
Metabolic and Endocrine 334308 334308 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised 1:1 to receive tirzepatide alongside usual insulin treatment (Group A) vs. insulin treatment alone (Group B) for 28 weeks duration. After a 4 week wash out period the groups will be swapped so that Group B receives study drug and Group A does not for a further 28 weeks. This will be followed by a 3-month follow-up period.

Tirzepatide will be self-administered via standard KwikPen injection once weekly. The dose incrementation of study drug will occur every 4 weeks, for each individual participant, commencing at a 2.5mg dose that will be up-titrated at 2.5mg dose increments to a maximum of a 10mg dose, so long as there are no adverse effects (commonly gastrointestinal side effects are experienced by participants). If significant side effects are experienced, the dosage of tirzepatide can be reduced to the maximally tolerated dose (MTD). One further attempt can be made to increase the dosage, at the discretion of the participant and investigator. The MTD will be held for the duration of the study.

To monitor adherence to the intervention all used/unused KwikPen devices will be returned to the investigators at the next scheduled study visit (occurring monthly). Both dispensing and return records will be kept by the study investigators.
Intervention code [1] 331370 0
Treatment: Drugs
Comparator / control treatment
This crossover study design will use the "untreated" arm as control. The control group will receive standard of care which include insulin administration and dietary advice.

Dietary advice will consist of 8x 20-minute face-to-face consultations with a registered dietician specialising in diabetes and obesity management. These will occur consecutively for 4-months at the start of each treatment period (Week 0, 4, 8, & 12 & Week 32, 36, 40 & 44).
Control group
Active

Outcomes
Primary outcome [1] 341972 0
Change in body weight (%)
Timepoint [1] 341972 0
End of each treatment period (Visit 10 -week 28 post-baseline vs Baseline -week 0 & visit 19-week 60 vs visit 11-week 32 post-baseline)
Secondary outcome [1] 449186 0
Change in CGM metrics, time-in-range
Timepoint [1] 449186 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [2] 449187 0
Change in insulin requirements
Timepoint [2] 449187 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [3] 449190 0
Change in Body mass index (BMI)
Timepoint [3] 449190 0
baseline, at each dose incrementation (visit 4, 5, 6, 7 & visit 13, 14, 15, 16), visit 10 (week 28 post-baseline), visit 19 (week 60 post-baseline), follow up (Week 64 & 72 post-baseline).
Secondary outcome [4] 449191 0
Change in Heart morphology
Timepoint [4] 449191 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [5] 449192 0
Changes in bone density
Timepoint [5] 449192 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [6] 449193 0
Urine marker, albumin:creatinine ratio
Timepoint [6] 449193 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [7] 449194 0
Identification of novel biomarkers related to TZP use in un-fasted blood samples (exploratory outcome)
Timepoint [7] 449194 0
visit 2 (week 0), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 16), visit 11 (week 32), visit 13 (week 36), visit 14 (week 40), visit 15 (week 44), and visit 16 (week 48) post-baseline.
Secondary outcome [8] 449195 0
Satisfaction with diabetes treatment
Timepoint [8] 449195 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [9] 449236 0
Ankle brachial index
Timepoint [9] 449236 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [10] 449237 0
Changes in liver mass
Timepoint [10] 449237 0
Baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [11] 449916 0
Change in HbA1C
Timepoint [11] 449916 0
Screening (2 weeks pre baseline), Visit 10 (week 28) and Visit 19 (week 60).
Secondary outcome [12] 449917 0
Change in CGM metrics, Time-below-range
Timepoint [12] 449917 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [13] 449918 0
Change in CGM metrics, Time-above-range
Timepoint [13] 449918 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [14] 449919 0
Change in waist circumference
Timepoint [14] 449919 0
baseline, at each dose incrementation (visit 4, 5, 6, 7 & visit 13, 14, 15, 16), visit 10 (week 28 post-baseline), visit 19 (week 60 post-baseline), follow up (Week 64 & 72 post-baseline).
Secondary outcome [15] 449920 0
Change in neck circumference
Timepoint [15] 449920 0
baseline, at each dose incrementation (visit 4, 5, 6, 7 & visit 13, 14, 15, 16), visit 10 (week 28 post-baseline), visit 19 (week 60 post-baseline), follow up (Week 64 & 72 post-baseline).
Secondary outcome [16] 449921 0
Change in Electrocardiogram (ECG) pattern
Timepoint [16] 449921 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [17] 449922 0
Change in blood pressure, systolic
Timepoint [17] 449922 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [18] 449923 0
Change in blood pressure, diastolic,
Timepoint [18] 449923 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [19] 449924 0
Change in mean arterial blood pressure
Timepoint [19] 449924 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [20] 449925 0
Change in heart rate
Timepoint [20] 449925 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [21] 449926 0
Changes in body fat %
Timepoint [21] 449926 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [22] 449927 0
Changes in lean mass %
Timepoint [22] 449927 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [23] 449928 0
Changes in muscle mass
Timepoint [23] 449928 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [24] 449929 0
Changes in % muscle fat infiltration
Timepoint [24] 449929 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [25] 449933 0
Identification of novel biomarkers associated with TZP use in urine samples (exploratory outcome)
Timepoint [25] 449933 0
visit 2 (week 0), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 16), visit 11 (week 32), visit 13 (week 36), visit 14 (week 40), visit 15 (week 44), and visit 16 (week 48) post-baseline.
Secondary outcome [26] 449934 0
Diabetes-associated distress
Timepoint [26] 449934 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [27] 449935 0
Impact of weight on quality of life
Timepoint [27] 449935 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [28] 449936 0
Cardiovascular disease risk
Timepoint [28] 449936 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [29] 449939 0
Arterial stiffness
Timepoint [29] 449939 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [30] 449940 0
Change in % liver fat infiltration (optional for the participant)
Timepoint [30] 449940 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [31] 449941 0
Routine blood marker, total cholesterol
Timepoint [31] 449941 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [32] 449942 0
Routine blood marker, LDL (Low-Density Lipoprotein)
Timepoint [32] 449942 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [33] 449943 0
Routine blood marker, HDL (High-Density Lipoprotein)
Timepoint [33] 449943 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [34] 450028 0
Routine blood test, EUC (Electrolytes Urea & Creatinine)
Timepoint [34] 450028 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [35] 450029 0
Routine blood test, TSH (Thyroid Stimulating Hormone)
Timepoint [35] 450029 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [36] 450030 0
Routine blood test, triglycerides
Timepoint [36] 450030 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [37] 450031 0
Routine blood test, FBC (Full blood count), B12, folate, iron, and vitamin D (Outcomes will be assessed separately)
Timepoint [37] 450031 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [38] 450034 0
Changes in nutritional intake - carbohydrate intake, protein intake, fibre intake, sodium intake (Outcomes will be assessed separately)
Timepoint [38] 450034 0
screening (2 weeks pre baseline), visit 10 (week 28), visit 19 (week 60) post-baseline.
Secondary outcome [39] 450273 0
Changes in muscle function - force, endurance, mobility and fitness (Outcomes will be assessed separately)
Timepoint [39] 450273 0
baseline, visit 10 (week 28), visit 19 (week 60) post-baseline.

Eligibility
Key inclusion criteria
• Age 18-70 years at screening
• A clinical diagnosis of T1D for at least 12 months at time of screening
• Body mass index greater than or equal to 27kg/m2
• HbA1c less than or equal to 10%
• Capable and willing to self-inject tirzepatide once per week
• In women of childbearing potential, a negative pregnancy test is required prior to commencing the study drug and every visit whilst receiving the study drug
• All participants must be willing to use effective contraception consistently for the duration of the study. Female participants of childbearing potential must agree to use highly effective measures of contraception consistently and correctly which will be documented by the study investigators.
• Able and willing to provide written informed consent for study participation
• Able and willing to use Easy Diet Diary
• Able and willing to keep an exercise log
• Willing to share devices data uploads
• Has current glucagon product to treat severe hypoglycaemia
• Has current ketone meters to check ketones
• Willingness to abstain from off-study glucagon-like peptide-1 (GLP1) use during their untreated phase
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Age < 18 years and > 70 years
• A clinical diagnosis of diabetes type other than T1D
• HbA1c > 10%
• Use of glucagon-like peptide-1 (GLP-1) receptor agonist within 3 months of study screening
• Use of any glucose lowering medications aside from insulin within 1 month of study screening
• History of hypersensitivity to investigational medicinal product or related product
• Obesity that is induced by other endocrine disorders
• Pregnancy or positive pregnancy test at time of screening, or unwilling to use effective contraception consistently for the duration of the study.
• Active proliferative diabetic retinopathy, maculopathy, or severe no proliferative diabetic retinopathy requiring acute treatment
• Known gastric emptying abnormality
• History of chronic or acute pancreatitis, uncontrolled hypertension, acute cardiovascular condition within 3 months
• Less than 12 months of insulin treatment
• Not willing to use a NovoPen 6 to record insulin dosing if currently using multiple daily injections
• Non compatible devices (e.g. pump, continuous glucose monitor (CGM) or smart phones) for data transfer
• Not willing to share device data
• Current use of any steroidal medication, or anticipated long-term steroidal treatment during the study period
• Serum triglycerides >500 mg/dL
• Planning for bariatric surgery during the study period
• eGFR <45 ml/min/1.73 m^2
• History of severe hypoglycaemia (within 3 months of trial period)
• History of diabetic ketoacidosis (within 3 months of trial period)
• History of stroke (within 3 months of trial period)
• History of congestive heart failure class III or IV
• Planned coronary, carotid, or peripheral artery revascularisation
• History of acute or chronic liver disease
• History of allergy to any form of insulin, GLP-1RA or its excipients
• History of malignancy requiring chemotherapy, surgery, or radiation (within 5 years of trial period)
• Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma
• Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia) within 5 years before screening
• Have a pacemaker, or metal implants
• Participation to other intervention trials during the study period
• Presence of any comorbidities or medical conditions, such as severe psychiatric disorders, that render a person unfit for the study at the discretion of the investigators.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation involved contacting the holder of the allocation schedule who was at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The participant numbers (nT = 60, 30/study arm) were powered based on weight reduction observed in the retrospective cohort study by S. K. Garg et al. The sample size formula used for this study compared two independent means with unequal variances to calculate the number of required study participants based on a significance level of 0.05 and a desired power of 80%. This was then increased to account for a 15% drop out rate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 28155 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 44364 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 319319 0
Hospital
Name [1] 319319 0
Royal North Shore Research Grants Scheme
Country [1] 319319 0
Australia
Funding source category [2] 319333 0
Hospital
Name [2] 319333 0
Department of Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital
Country [2] 319333 0
Australia
Primary sponsor type
Hospital
Name
Department of Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital
Address
Country
Australia
Secondary sponsor category [1] 321797 0
None
Name [1] 321797 0
Address [1] 321797 0
Country [1] 321797 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317899 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 317899 0
Ethics committee country [1] 317899 0
Australia
Date submitted for ethics approval [1] 317899 0
28/10/2024
Approval date [1] 317899 0
29/07/2025
Ethics approval number [1] 317899 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142506 0
A/Prof Sarah J Glastras
Address 142506 0
Department of Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital, Reserve Rd, St Leonards NSW 2065
Country 142506 0
Australia
Phone 142506 0
+61 0425255625
Fax 142506 0
Email 142506 0
Contact person for public queries
Name 142507 0
Matilda Longfield
Address 142507 0
Department of Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital, Reserve Rd, St Leonards NSW 2065
Country 142507 0
Australia
Phone 142507 0
+61 0447123258
Fax 142507 0
Email 142507 0
Contact person for scientific queries
Name 142508 0
Sarah J Glastras
Address 142508 0
Department of Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital, Reserve Rd, St Leonards NSW 2065
Country 142508 0
Australia
Phone 142508 0
+61 0425255625
Fax 142508 0
Email 142508 0

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
Researchers
Conditions for requesting access:
Yes, conditions apply:
Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
What individual participant data might be shared?
De-identified individual participant data:
Published results
What types of analyses could be done with individual participant data?
Systematic reviews and meta-analyses
Studies exploring new research questions
Studies testing whether findings can be repeated or confirmed
Teaching research methods or developing new statistical techniques
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
Email of trial custodian, sponsor or committee: A.Prof Sarah Glastras [email protected]

Are there extra considerations when requesting access to individual participant data?
Yes: Some specific data may not be available for sharing due to data storage policies determined by the NSLHD HREC committee.



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.