Tirzepatide Use in People With Obesity and Type 1 Diabetes

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities.

2. Male or female, adults.

3. Documented diagnosis of T1DM (per ADA 2024definition/criteria) for at least 1 yearbefore screening visit with C-peptide level of less than 0.01nm/L.

4. Body mass index (BMI) ≥ 27.0 kg/m2

5. History of at least one self-reported unsuccessful dietary effort to lose bodyweight.

6. Must be using a Continuous Glucose Monitoring (CGM) device for at least 2 monthsbefore the screening visit and be willing to wear a CGM device for the duration ofthe study.

Exclusion Criteria:

1. Diabetes related:

• Glycated hemoglobin (HbA1c) ≥86 mmol/mol (10%) as measured by the centrallaboratory at screening.

• Treatment with a glucagon-like peptide-1 receptor agonist within 180 daysbefore screening.

• Preproliferative or proliferative retinopathy

• Experienced diabetic ketoacidosis within 6 months of screening visit.

• Experienced severe hypoglycemia (Level 3) within 6 months of screening visit.

2. Obesity-related:

• A self-reported change in body weight >5 kg (11 lbs) within 90 days beforescreening irrespective of medical records.

• Treatment with any medication for the indication of obesity within the past 90days before screening.

• Previous or planned (during the trial period) obesity treatment with surgery ora weight-loss device. However, the following are allowed: (1) liposuctionand/or abdominoplasty, if performed >1 year before screening; (2) lap banding,if the band has been removed >1 year before screening; (3) intragastricballoon, if the balloon has been removed >1 year before screening; or (4)duodenal-jejunal bypass sleeve, if the sleeve has been removed >1 year beforescreening.

• Uncontrolled thyroid disease, defined as thyroid stimulating hormone >6.0 mIU/Lor <0.4 mIU/L as measured by the central laboratory at screening.

3. Mental health:

• History of major depressive disorder within 2 years before screening.

• Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolardisorder).

• A Patient Health Questionnaire-9 score of ≥15 at screening.

• A lifetime history of a suicidal attempt.

• Suicidal behavior within 30 days before screening.

• Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide SeverityRating Scale within the past 30 days before screening.

4. General safety:

• Use of non-herbal Chinese medicine or other non-herbal local medicine withunknown/unspecified content within 90 days before screening.

• Presence of acute pancreatitis within the past 180 days prior to the day ofscreening.

• History or presence of chronic pancreatitis.

• Calcitonin ≥100 ng/L as measured by the central laboratory at screening.

• Personal or first-degree relative(s) history of multiple endocrine neoplasiatype 2 or medullary thyroid carcinoma.

• Renal impairment measured as estimated glomerular filtration rate value of <15mL/min/1.73m2 as defined by KDIGO 2012 by the central laboratory at screening.

• History of malignant neoplasms within the past 5 years prior to screening.Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.

• Any of the following: myocardial infarction, stroke, hospitalization forunstable angina, or transient ischemic attack within the past 60 days prior toscreening.

• Subject presently classified as being in New York Heart Association Class IV.

• Surgery scheduled for the duration of the trial, except for minor surgicalprocedures, in the opinion of the investigator.

• Known or suspected abuse of alcohol or recreational drugs.

• Known or suspected hypersensitivity to trial product(s) or related products.

• Previous participation in this trial. Participation is defined as signedinformed consent.

• Participation in another clinical trial within 90 days before screening.

• Other subject(s) from the same household participating in any semaglutidetrial.

• Female who is pregnant, breast-feeding, or intends to become pregnant, or is ofchild-bearing potential and not using a highly effective contraceptive method.

• Any disorder, unwillingness, or inability, not covered by any of the otherexclusion criteria, which in the investigator's opinion, might jeopardize thesubject's safety or compliance with the protocol.