Tirzepatide for the Treatment of Concurrent Type 1 Diabetes and Overweight or Obesity

Official title

Tirzepatide for the Treatment of Concurrent Type 1 Diabetes and Overweight or Obesity: A Placebo-Matched Randomised Controlled Trial

Overview

This study is a 2-arm, double blinded, randomised clinical trial where 40 participants will be assigned 1:1 to insulin treatment alone (control) or insulin treatment and tirzepatide treatment for 32 weeks. The primary objective is to demonstrate that tirzepatide treatment, dose incremented to 15mg QW for 32 weeks adjunctive to insulin treatment can reduce body weight in patients with T1D and overweight or obesity when compared to insulin treatment alone. The secondary objective is to demonstrate that tirzepatide treatment, dose incremented to 15mg QW for 32 weeks can improve glycaemic control (measured by hbA1c), improve time in range, reduce insulin requirements, and reduce the severity of comorbidities in people with obesity and T1D. This trial includes a 6 month follow-up period.

Interventions

• Drug Tirzepatide
  Tirzepatide will be self-administered subcutaneously by study participants via an injection. The drug will be taken weekly following the schedule: 4 weeks at 2.5 mg QW, 4 weeks at 5.0 mg QW, 4 weeks at 7.5 mg QW, 4 weeks at 10.0 mg QW, 4 weeks at 12.5 mg QW, 12 weeks at 15 mg QW. Modification of study drug will be performed if the participant is experiencing significant side effects and cannot tolerate the higher dosage of the study drug. In this instance, the study drug dosage will be reduced

Primary outcome measures

• Body weight [Time frame: 32 weeks]

Secondary outcome measures (12)

• hbA1c [Time frame: 32 weeks]
• Time in range [Time frame: 32 weeks]
• Total daily insulin dose [Time frame: 32 weeks]
• Insulin carbohydrate ratio [Time frame: 32 weeks]
• Waist and neck circumference [Time frame: 32 weeks]
• Blood pressure [Time frame: 32 weeks]
• Mean glucose [Time frame: 32 weeks]
• Time in hypoglycaemia [Time frame: 32 weeks]
• Time in hyperglycaemia [Time frame: 32 weeks]
• Continuous glucose monitoring [Time frame: 32 weeks]
• Continuous glucose monitoring [Time frame: 32 weeks]
• Continuous glucose monitoring [Time frame: 32 weeks]

Eligibility criteria

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 ≥ 27kg/m2
• HbA1c ≤ 10%
• Capable and willing to self-inject tirzepatide once per week
• In women of childbearing potential, a negative pregnancy test and willing to use effective contraception consistently for the duration of the study
• 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

Exclusion criteria

• Age <18 years and >70 years
• A clinical diagnosis of diabetes type other than T1D
• HbA1c > 10%
• Use of GLP-1 receptor agonist within 1 month 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 which is defined in Appendix 1
• 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
• No longer than 12 months of insulin treatment
• Not willing to use a NovoPen 6 to record insulin dosing if currently using multiple daily injections
• Insulin pump, CGM or smart phone devices are not compatible for data transfer
• Not willing to share device data
• Current use of any steroidal medication, or planned long-term steroidal treatment (>4 weeks) during the study period
• Serum triglycerides >500 mg/dL
• History of or plans for bariatric surgery during the study period
• eGFR <45 ml/min/1.73 m2
• 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 heart failure
• 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)
• History of multiple endocrine neoplasia type 2, familial thyroid cancer, or non-familial medullary thyroid cancer
• 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 in other intervention trials during the study period
• Existence of any additional health conditions or medical issues, including significant psychiatric disorders, that render a person unfit for the study at the discretion of the investigators

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Purcell AR, Rodrigo N, Longfield MSG, Glastras SJ. Tirzepatide for the treatment of adults living with concurrent type 1 diabetes and overweight or obesity (TZP-T1D): a double-blind, placebo-matched randomised controlled trial protocol. BMJ Open. 2025 Sep 16;15(9):e093775. doi: 10.1136/bmjopen-2024-093775. PMID 40962353

Identifiers

NCT: NCT06180616 · TZP-T1D

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗