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

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 useeffective 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 studyscreening

• 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 useeffective contraception consistently for the duration of the study which is definedin Appendix 1

• Active proliferative diabetic retinopathy, maculopathy, or severe no proliferativediabetic retinopathy requiring acute treatment

• Known gastric emptying abnormality

• History of chronic or acute pancreatitis, uncontrolled hypertension, acutecardiovascular 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 multipledaily 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 yearsof trial period)

• History of multiple endocrine neoplasia type 2, familial thyroid cancer, ornon-familial medullary thyroid cancer

• Presence or history of malignant neoplasms or in situ carcinomas (other than basalor squamous cell skin cancer, low-risk prostate cancer, or in situ carcinomas of thecervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia) within 5years 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, includingsignificant psychiatric disorders, that render a person unfit for the study at thediscretion of the investigators