Tirzepatide for the Treatment of Concurrent Type 1 Diabetes and Overweight or Obesity (TZP-T1D)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 1 Diabetes Mellitus; Overweight and Obesity
• Intervention / Treatment: Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Insulin Treatment; Participants will remain on their typical insulin therapy regime for 32 weeks
Experimental: Tirzepatide Treatment; Participants will remain on their typical insulin therapy regime and will also receive tirzepatide (dose incremented to 15mg QW) for 32 weeks.	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 to the previously tolerated dosage and held at this dose for a further 4 weeks. One further attempt at dose escalation will be undertaken after 4 weeks, at the discretion of the participant and the study investigator. If recurrent side effects are experienced by the participant, the study drug will be returned to the previously tolerated dosage, and the prescription continued at this dosage for the remainder of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Percent body weight change (%)	32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in range	Change in continuous glucose monitoring (CGM) metrics (time in range (3.9-10mmol/L))	32 weeks
Total daily insulin dose	Change in insulin dose (total daily dose, units/kg of body weight)	32 weeks
Insulin carbohydrate ratio	Change in insulin dose (insulin carbohydrate ratio (units per g))	32 weeks
Waist and neck circumference	Change in waist and neck circumference	32 weeks
Blood pressure	Change in blood pressure	32 weeks
Mean glucose	Change in continuous glucose monitoring (CGM) metrics (mean glucose)	32 weeks
Time in hypoglycaemia	Change in continuous glucose monitoring (CGM) metrics (time in hypoglycaemia (mild < 3.9, severe < 2.5mmol/L))	32 weeks
Time in hyperglycaemia	Change in continuous glucose monitoring (CGM) metrics (time in hyperglycaemia (mild >10, severe 13.9mmol/L))	32 weeks
Continuous glucose monitoring	Change in continuous glucose monitoring (CGM) metrics (SD)	32 weeks
Continuous glucose monitoring	Change in continuous glucose monitoring (CGM) metrics (CV)	32 weeks
Continuous glucose monitoring	Change in continuous glucose monitoring (CGM) metrics (CONGA)	32 weeks
Continuous glucose monitoring	Change in continuous glucose monitoring (CGM) metrics (J-index)	32 weeks
Continuous glucose monitoring	Change in continuous glucose monitoring (CGM) metrics (MAGE)	32 weeks
Total cholesterol	Change in lipid parameters (total cholesterol)	32 weeks
Triglyceride	Change in lipid parameters (triglyceride)	32 weeks
LDL-C	Change in lipid parameters (LDL-C)	32 weeks
HDL-C	Change in lipid parameters (HDL-C)	32 weeks
ACR	Change in albumin to creatinine ratio (ACR)	32 weeks
eGFR	Change in renal function (eGFR)	32 weeks
HSI	Change in NAFLD biomarker HSI. Hepatic steatosis defined as HSI > 36	32 weeks
FIB-4	Change in NAFLD biomarker FIB-4. Hepatic steatosis defined as FIB-4 index ≥ 1.3 or < 1.3	32 weeks
hbA1c	Change in hbA1c levels (%)	32 weeks
Brachial-Ankle Pulse Wave Velocity using Ankle Brachial Index Machine	Change in Brachial-Ankle Pulse Wave Velocity (baPWV)	32 weeks
Arterial Stiffness using a Pulse Wave Tonometer	Change in arterial stiffness	32 weeks
Aortic Stiffness using a Pulse Wave Tonometer	Change in aortic stiffness	32 weeks
Left Ventricular Strain using Electrocardiogram	Change in left ventricular strain	32 weeks

Collaborators and Investigators

• Sponsor: Royal North Shore Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: December 20, 2023
• First Posted (Actual): December 22, 2023

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 24, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Tirzepatide; GLP-1/GIP Agonist
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Overweight; Obesity; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: TZP-T1D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data related to the primary and secondary outcomes may be shared upon reasonable request following publication. Data sharing will be considered for ethically approved research purposes and subject to data use agreements. IPD will not be shared if legal, ethical, or institutional constraints prevent it.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No