Overweight and Obesity, Type 1 Diabetes Mellitus
Conditions
Keywords
Tirzepatide, GLP-1/GIP Agonist
Brief summary
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
DRUGTirzepatide
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.
Sponsors
Royal North Shore Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body weight | 32 weeks | Percent body weight change (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time in range | 32 weeks | Change in continuous glucose monitoring (CGM) metrics (time in range (3.9-10mmol/L)) |
| Total daily insulin dose | 32 weeks | Change in insulin dose (total daily dose, units/kg of body weight) |
| Insulin carbohydrate ratio | 32 weeks | Change in insulin dose (insulin carbohydrate ratio (units per g)) |
| Waist and neck circumference | 32 weeks | Change in waist and neck circumference |
| Blood pressure | 32 weeks | Change in blood pressure |
| Mean glucose | 32 weeks | Change in continuous glucose monitoring (CGM) metrics (mean glucose) |
| Time in hypoglycaemia | 32 weeks | Change in continuous glucose monitoring (CGM) metrics (time in hypoglycaemia (mild \< 3.9, severe \< 2.5mmol/L)) |
| Time in hyperglycaemia | 32 weeks | Change in continuous glucose monitoring (CGM) metrics (time in hyperglycaemia (mild \>10, severe 13.9mmol/L)) |
| Continuous glucose monitoring | 32 weeks | Change in continuous glucose monitoring (CGM) metrics (SD) |
| Total cholesterol | 32 weeks | Change in lipid parameters (total cholesterol) |
| hbA1c | 32 weeks | Change in hbA1c levels (%) |
| LDL-C | 32 weeks | Change in lipid parameters (LDL-C) |
| HDL-C | 32 weeks | Change in lipid parameters (HDL-C) |
| ACR | 32 weeks | Change in albumin to creatinine ratio (ACR) |
| eGFR | 32 weeks | Change in renal function (eGFR) |
| HSI | 32 weeks | Change in NAFLD biomarker HSI. Hepatic steatosis defined as HSI \> 36 |
| FIB-4 | 32 weeks | Change in NAFLD biomarker FIB-4. Hepatic steatosis defined as FIB-4 index ≥ 1.3 or \< 1.3 |
| Brachial-Ankle Pulse Wave Velocity using Ankle Brachial Index Machine | 32 weeks | Change in Brachial-Ankle Pulse Wave Velocity (baPWV) |
| Arterial Stiffness using a Pulse Wave Tonometer | 32 weeks | Change in arterial stiffness |
| Aortic Stiffness using a Pulse Wave Tonometer | 32 weeks | Change in aortic stiffness |
| Left Ventricular Strain using Electrocardiogram | 32 weeks | Change in left ventricular strain |
| Triglyceride | 32 weeks | Change in lipid parameters (triglyceride) |
Outcome results
None listed