None listed
Conditions
Brief summary
The prevalence of obesity in patients with T1D is increasing. The common consequences of obesity in individuals with T1D include, insulin resistance, increased insulin requirements and impaired glycaemic control, increasing the risk of diabetes-related complications in these individuals. Novel therapeutic strategies that reduce body weight and synergistically aid insulin therapy in improving glycaemic control are therefore needed to address this challenge and reduce their risk of life-threatening diabetic complications. Tirzepatide is an incretin-based therapy commonly used in patients with type 2 diabetes and/or obesity that has proven effective for reducing body weight and improving glycaemic control. Therefore, this study aims to evaluate the efficacy of tirzepatide in individuals with concurrent T1D and overweight or obesity who are receiving insulin therapy in a cross-over randomised study design. The aim is to evaluate if adjunctive insulin therapy with tirzepatide can lead to a reduction in body weight and improved metabolic outcomes compared to insulin treatment alone.
Interventions
Participants will be randomised 1:1 to receive tirzepatide alongside usual insulin treatment (Group A) vs. insulin treatment alone (Group B) for 28 weeks duration. After a 4 week wash out period the groups will be swapped so that Group B receives study drug and Group A does not for a further 28 weeks. This will be followed by a 3-month follow-up period.
Tirzepatide will be self-administered via standard KwikPen injection once weekly. The dose incrementation of study drug will occur every 4 wee
Participants will be randomised 1:1 to receive tirzepatide alongside usual insulin treatment (Group A) vs. insulin treatment alone (Group B) for 28 weeks duration. After a 4 week wash out period the groups will be swapped so that Group B receives study drug and Group A does not for a further 28 weeks. This will be followed by a 3-month follow-up period. Tirzepatide will be self-administered via standard KwikPen injection once weekly. The dose incrementation of study drug will occur every 4 weeks, for each individual participant, commencing at a 2.5mg dose that will be up-titrated at 2.5mg dose increments to a maximum of a 10mg dose, so long as there are no adverse effects (commonly gastrointestinal side effects are experienced by participants). If significant side effects are experienced, the dosage of tirzepatide can be reduced to the maximally tolerated dose (MTD). One further attempt can be made to increase the dosage, at the discretion of the participant and investigator. The MTD will be held for the duration of the study. To monitor adherence to the intervention all used/unused KwikPen devices will be returned to the investigators at the next scheduled study visit (occurring monthly). Both dispensing and return records will be kept by the study investigators.
Sponsors
Department of Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
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 greater than or equal to 27kg/m2 • HbA1c less than or equal to 10% • Capable and willing to self-inject tirzepatide once per week • In women of childbearing potential, a negative pregnancy test is required prior to commencing the study drug and every visit whilst receiving the study drug • All participants must be willing to use effective contraception consistently for the duration of the study. Female participants of childbearing potential must agree to use highly effective measures of contraception consistently and correctly which will be documented by the study investigators. • 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 • Willingness to abstain from off-study glucagon-like peptide-1 (GLP1) use during their untreated phase
Exclusion criteria
• Age < 18 years and > 70 years • A clinical diagnosis of diabetes type other than T1D • HbA1c > 10% • Use of glucagon-like peptide-1 (GLP-1) receptor agonist within 3 months 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. • 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 • Less than 12 months of insulin treatment • Not willing to use a NovoPen 6 to record insulin dosing if currently using multiple daily injections • Non compatible devices (e.g. pump, continuous glucose monitor (CGM) or smart phones) for data transfer • Not willing to share device data • Current use of any steroidal medication, or anticipated long-term steroidal treatment during the study period • Serum triglycerides >500 mg/dL • Planning for bariatric surgery during the study period • eGFR <45 ml/min/1.73 m^2 • 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 congestive heart failure class III or IV • 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) • Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma • 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 to other intervention trials during the study period • Presence of any comorbidities or medical conditions, such as severe psychiatric disorders, that render a person unfit for the study at the discretion of the investigators.
Outcome results
None listed