Fully Closed-Loop Glucose Control in Adults With Type 1 Diabetes Using Tirzepatide: a Randomized, Multi-center, Open-label, Non-inferiority, Parallel Trial

Official Summary

This research study is testing whether a weekly medication called tirzepatide can help adults with type 1 diabetes use their insulin pump more easily, specifically by reducing or eliminating the need to count carbohydrates at meals. People with type 1 diabetes must take insulin for life, and even with advanced insulin pumps and continuous glucose monitors, many still struggle to keep blood sugar within the target range. One of the biggest challenges is carbohydrate counting, which requires estimating the amount of carbohydrates in every meal to give the correct insulin dose. Tirzepatide is a medication currently approved for type 2 diabetes and weight management. Early research suggests it may also help people with type 1 diabetes by lowering appetite, slowing digestion, reducing insulin needs, and smoothing after-meal blood sugar rises. This study will include 105 adults with type 1 diabetes at centers in Canada and Switzerland. Everyone will use the Tandem Control-IQ insulin pump with a Dexcom G7 continuous glucose monitor. Participants are randomly assigned to one of two groups: Tirzepatide group: Participants receive weekly tirzepatide injections. After the dose is gradually increased over 12 weeks, they will eventually try using their insulin pump without entering carbohydrate amounts at meals. Control group: Participants continue their usual therapy and keep counting carbohydrates for their mealtime insulin doses. The main goal of the study is to learn whether people taking tirzepatide can safely maintain good blood sugar control without counting carbs, compared with standard care. All participants will attend several clinic visits and share their glucose, insulin, and health data throughout the 32-week trial. Some centers will also conduct heart/fitness, or body-composition tests. As with any medication, tirzepatide may cause side effects such as nausea, vomiting, diarrhea, or decreased appetite. Rare but serious risks like gallbladder disease or pan

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 105 participants

Study Arms

• Tirzepatide group (EXPERIMENTAL)
  Participants randomized to this arm receive once-weekly subcutaneous tirzepatide in addition to use of the Tandem Control-IQ insulin pump and Dexcom G7 continuous glucose monitor. Tirzepatide is initiated at 2.5 mg weekly and increased by 2.5 mg every 4 weeks to a target dose of 10 mg weekly or the maximally tolerated dose. Dose escalation may be delayed or reduced if participants experience intolerable gastrointestinal symptoms. During Weeks 1-26, participants continue standard carbohydrate cou
• Control group (ACTIVE_COMPARATOR)
  Participants randomized to the control arm use the Tandem Control-IQ automated insulin delivery system with the Dexcom G7 continuous glucose monitor, following standard-of-care diabetes management. They continue carbohydrate counting for all meals throughout the 32-week study and deliver prandial insulin boluses based on estimated carbohydrate intake, as is typical for users of hybrid closed-loop systems. No tirzepatide injections are administered. Participants receive the same device training,

Interventions

• DRUG: Tirzepatide — Tirzepatide, administered as a once-weekly subcutaneous injection, initiated at 2.5 mg and escalated in 2.5-mg increments every 4 weeks to a target of 10 mg or the maximally tolerated dose, used as an adjunct therapy in adults with type 1 diabetes using the Tandem Control-IQ automated insulin delivery system.
• DEVICE: Tandem Control-IQ Automated Insulin Delivery System (with Dexcom G7 CGM) — This intervention uses the Tandem t:slim X2 insulin pump with the Control-IQ automated insulin delivery algorithm, integrated with the Dexcom G7 continuous glucose monitor. The system adjusts basal insulin and delivers automated correction boluses based on real-time glucose values. All participants receive standardized training and use this system for the full 32-week study. Rapid-acting insulin compatible with Control-IQ is required. This intervention is distinguished by its use under two diffe
• BEHAVIORAL: Carbohydrate Counting — Participants enter the estimated carbohydrate amount for every meal and snack into the Tandem Control-IQ insulin pump to calculate and deliver prandial insulin boluses. This reflects standard use of hybrid closed-loop systems. The procedure is maintained for the entire 32-week study in the control arm and during Weeks 1-26 in the tirzepatide arm.
• BEHAVIORAL: No Meal Announcement — Participants do not enter carbohydrate amounts or announce meals to the Tandem Control-IQ system. The pump operates without user-initiated prandial boluses, relying solely on automated basal adjustments and automated correction boluses. This intervention is implemented only in the tirzepatide arm during Weeks 27-32.

Primary Outcomes

• Daytime Time-in-Range (During the final 6 weeks of the study)

Secondary Outcomes

• Weight (At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study)
• Height (At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study.)
• Body Mass Index (At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study)
• Waist circumference (At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study)
• Waist-to-Hip Ratio (At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study.)

Eligibility Criteria

Inclusion Criteria:

* Age ≥ 18 years.
* Clinical diagnosis of type 1 diabetes for ≥ 1 year, per investigator judgment (confirmatory C-peptide and autoantibodies not required).
* A BMI ≥ 27 kg/m2.
* HbA1c \> 6.5%, and \< 12%.
* Current therapy: multiple daily injections or insulin pump.
* Willingness to use Tandem Control IQ insulin pump system with the use of rapid or ultra rapid-acting insulins compatible with Tandem Control-IQ pump (e.g. Fiasp is not compatible)
* Active carbohydrate counting for prandial insulin dosing.
* Individuals of childbearing potential must be using or agree to use an effective birth-control method. Childbearing potential refers to participants of the female sex post-menarche who have not reached menopause and who do not have a medical condition causing sterility (e.g., hysterectomy). Post-menopausal state refers to the absence of menses for 12 months without any alternative cause.

Exclusion Criteria:

* Use of GLP1-RAs within the last four weeks.
* Use of antihyperglycemic agents other than insulin or metformin within the last 2 weeks.
* Planned or ongoing pregnancy.
* Breastfeeding.
* Severe hypoglycemia requiring hospitalization in the past 2 months. Severe hypoglycemia is defined as requiring the assistance of another person, due to altered consciousness, to administer carbohydrates, glucagon, or other resuscitative actions.
* Diabetic ketoacidosis within the last 2 months.
* History of acute or chronic pancreatitis.
* Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
* Severe renal impairment with eGFR \<30 mL/min/1.73 m2 (CKD-EPI), measured within the last four months.
* Clinically significant proliferative diabetic retinopathy or gastroparesis, as per the judgment of the investigator.
* Current or ≤ 1 month use of supraphysiological doses of oral or intravenous glucocorticoids.
* History of bariatric surgery within the last 6 months.
* Medical or psychiatric illness likely to interfere with participation (e.g. cirrhosis, active cancer, decompensated schizophrenia), per investigator judgment.
* Inability or unwillingness to comply with safe diabetes management practices, in the view of the investigator.
* Any safety concern that, in the investigator's judgment, precludes participation.

Trial Locations

• Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada
• McGill University Health Centre, Montreal, Quebec, Canada
• Insel Hospital, University Hospital Bern, Bern, Switzerland

Contact Information

• Keddy Moise, MD — CONTACT
  Phone: 438-531-6896
  Email: keddy.moise@affiliate.mcgill.ca
• Carolyn Wright, Bachelor of Science — CONTACT
  Phone: 514-318-7298
  Email: carolyn.wright@mail.mcgill.ca

Study Officials

• Melissa-Rosina Pasqua, MD-PhD — PRINCIPAL_INVESTIGATOR
  McGill University Health Centre/Research Institute of the McGill University Health Centre
• Ahmad Haidar, PhD — STUDY_DIRECTOR
  McGill University Health Centre/Research Institute of the McGill University Health Centre

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