Tirzepatide for the Concurrent Treatment of Obesity and Type 1 Diabetes

Study Overview
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Brief Summary
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This study is a 2-arm, double blinded, randomised clinical trial where 36 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 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.

Official Title
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Tirzepatide for the Concurrent Treatment of Obesity and Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus, Obesity

Intervention / Treatment
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* Drug: Tirzepatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years at screening A clinical diagnosis of T1DM for at < 12 months at time of screening Body mass index ≥ 30kg/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 which is defined as: an intrauterine device, oral contraceptive pill, or combination of two barrier methods with one being male condom 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 Patient on hybrid closed loop system for >3 months Willing to share devices data uploads Has current glucagon product to treat severe hypo Has current ketone meters to check ketones Exclusion Criteria: Age < 18 years and > 70 years A clinical diagnosis of diabetes type other than T1DM 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 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 as: an intrauterine device, oral contraceptive pill, or combination of two barrier methods with one being male condom Active proliferative diabetic retinopathy, maculopathy or severe NPDR 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, 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 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) 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Insulin Treatment<br>Participants will remain on their typical insulin therapy regime for 32 weeks | |
| Experimental: Tirzepatide Treatment<br>Participants will remain on their typical insulin therapy regime and will also receive tirzepatide (dose incremented to 15mg QW) for 32 weeks. | Drug: Tirzepatide<br>* 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. If gastrointestinal adverse effects occur during dose escalation, the dose can be held at the lowest tolerable dose for a longer period (up to 3 weeks) until an increment can be tolerated (analysis will be by intention to treat).<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| hbA1c | Change in hbA1c levels | 32 weeks | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tirzepatide, GLP-1/GIP Agonist