None listed
Conditions
Brief summary
This study aims to determine whether a medication called tirzepatide is effective for weight loss, improving blood glucose levels, and improving metabolic health in people with type 1 diabetes and overweight/obesity. This study will also look at the effects of tirzepatide plus an exercise program on weight loss and changes in the proportion of muscle and body fat seen with tirzepatide, and how continued participation in this exercise program after stopping tirzepatide treatment affects body weight and body composition. We hypothesise that tirzepatide will lead to significant weight loss benefits in comparison to usual care in adults with type 1 diabetes and overweight/obesity.
Interventions
12 week treatment period:
• Arm 1: receive low dose tirzepatide (2.5mg subcutaneous injection weekly for 4 weeks, then 5mg subcutaneous injection weekly for 8 weeks) in addition to usual care. Tirzepatide adherence will be monitored via used vial/pen return.
• Arm 2: first undergo a 12 week Usual Care Control Period, then proceed to receive low dose tirzepatide (2.5mg subcutaneous injection weekly for 4 weeks, then 5mg subcutaneous injection weekly for 8 weeks) and participate in a tailored exe
12 week treatment period: • Arm 1: receive low dose tirzepatide (2.5mg subcutaneous injection weekly for 4 weeks, then 5mg subcutaneous injection weekly for 8 weeks) in addition to usual care. Tirzepatide adherence will be monitored via used vial/pen return. • Arm 2: first undergo a 12 week Usual Care Control Period, then proceed to receive low dose tirzepatide (2.5mg subcutaneous injection weekly for 4 weeks, then 5mg subcutaneous injection weekly for 8 weeks) and participate in a tailored exercise program, in addition to usual care. Tirzepatide adherence will be monitored via used vial/pen return. Participants randomised to the tirzepatide + exercise arm will receive at least 1 x 30 to 60 mins 1:1 session with the exercise physiologist at the research clinic for an initial assessment and to receive education on how to complete a tailored exercise program at home consisting of both aerobic exercises (e.g. treadmill) and resistance exercises (e.g. resistance bands, lifting weights). Exercises performed will be tailored to the participant's capabilities and preferences. During the aerobic exercise assessment, the exercise physiologist will assess for suitable "moderate intensity" power and subsequent exercise power will be prescribed based on HR and/or RPE. A brief strength assessment will be used to dictate prescribed load. Participants will be invited to participate in further group sessions with a maximum of 12 participants (30 to 60 mins twice weekly for at least first 2 weeks of program). Adherence will be monitored via attendance records (for sessions with exercise physiologist) as well as Fitbit metrics (for home-based exercise). Participants will be advised to perform 45 to 60 mins of exercise on 3 to 6 days of the week. 12 week follow-up period: • Arm 1: cease tirzepatide and continue with usual care. • Arm 2: cease tirzepatide but continue with exercise program in addition to usual care. The exercise program will continue for a total 24 weeks (12 weeks intervention period and 12 weeks follow-up period).
Sponsors
Sydney Local health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
• men and women aged 18 to 70 years (inclusive) • on basal bolus insulin or continuous insulin infusion via a subcutaneous insulin pump. • able to provide informed consent according to local regulations • documented diagnosis of type 1 diabetes mellitus (T1DM) using World Health Organization classification criteria or other local guidelines, with date of diagnosis at least 12 months prior to enrolment date • body mass index (BMI) greater than or equal to 25 kg/m2 (or greater than or equal to 23 kg/m2 in Asians and Indigenous Australians) • HbA1c greater than or equal to 6.5% at or within 3 months of Visit 1.
Exclusion criteria
• weight loss or weight gain of > 5% of total body weight within the past 3 months • current use of GLP-1 RAs or anti-obesity drugs • history of chronic pancreatitis or acute pancreatitis • history of pancreatic malignancy • history of pancreas surgery • known proliferative retinopathy or diabetic maculopathy • nonproliferative diabetic retinopathy that required acute treatment within the past 12 months • history of ketoacidosis or hyperosmolar hyperglycaemic state within the past 12 months • history of severe hypoglycaemia within 3 months prior to Visit 1 (defined as hypoglycaemia requiring assistance from others to treat) • history of a clinically significant gastric emptying abnormality • history of bariatric surgery • chronic use of medications that directly affect gastrointestinal motility • eGFR < 30 ml/min/1.73 m2 • acute coronary/cerebrovascular event or hospitalisation due to congestive heart failure within previous 3 months prior to enrolment • planned coronary, carotid, or peripheral artery revascularization • New York Heart Association (NYHA) Class III or IV Heart Failure • any liver disease other than metabolic-associated fatty liver disease (MAFLD). Those with end-stage liver disease will be excluded. • symptomatic gallbladder disease • prior organ transplant (corneal transplants allowed) • evidence of a significant and active condition that, in the opinion of the investigator, is likely to require concurrent and/or recurrent treatment with systemic glucocorticoids in the next 12 months • receiving chronic (> 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, or inhaled preparations) or have received such therapy within 1 month of Visit 1 • have evidence of a significant uncontrolled medical condition in the opinion of the investigator • known eating disorder or disordered eating behaviours • personal or family history of Multiple Endocrine Neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma • personal history of non-familial medullary thyroid carcinoma • diagnosis of malignant neoplasm in the previous 5 years (except non-metastatic basal cell skin cancer or squamous cell skin cancer) • women of childbearing potential who are pregnant, breast-feeding, intend to become pregnant during the trial period or 3 months after the last dose of tirzepatide, or does not agree to use adequate contraceptive in the opinion of the investigators. • unable to use CGM • unable to test capillary glucose and ketones • physical disability, cognitive impairment, psychiatric condition, or other reason precluding adequate understanding of, or compliance with, study procedures in the opinion of the investigator • any other condition (e.g. known illicit drug or alcohol abuse) that in the opinion of the investigator, may preclude the patient from following and completing the protocol
Outcome results
None listed