Fully Closed-Loop Glucose Control in Adults With Type 1 Diabetes Using Tirzepatide: a Randomized, Multi-center, Open-label, Non-inferiority, Parallel Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 105
- 试验地点
- 7
- 主要终点
- Daytime Time-in-Range
研究概览
简要总结
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 pancreatitis are also monitored. Pregnancy must be avoided during the trial.
Overall, this study aims to understand whether adding tirzepatide to automated insulin delivery can simplify diabetes management, reduce burden, and maintain safe and effective glucose control for adults living with type 1 diabetes.
详细描述
Current diabetes technology, including hybrid automated insulin delivery systems like the Tandem Control-IQ paired with the Dexcom G7 continuous glucose monitor, improves glucose control but still relies heavily on patients entering carbohydrate amounts before eating, a task that is difficult, error-prone, and often stressful.
Tirzepatide, which is approved for type 2 diabetes and weight management, works by slowing digestion, lowering appetite, reducing insulin requirements, and improving after-meal glucose spikes, and early evidence suggests it may offer similar benefits in type 1 diabetes. This study is designed to determine whether adding once-weekly tirzepatide injections to a commercially available automated insulin delivery system can make diabetes management easier for adults with type 1, particularly by reducing or eliminating the need to count carbohydrates at meals.
In this 32-week trial, 105 adults will be randomly assigned to receive tirzepatide or no tirzepatide while all participants use the Control-IQ system. Those receiving tirzepatide will gradually increase their dose over 12 weeks, continue counting carbohydrates until week 26, and then stop announcing meals entirely for the final 6 weeks, while the control group will count carbohydrates throughout.
Across the study, participants will attend scheduled clinic visits, complete remote follow-ups, undergo laboratory tests, and, depending on the site, may complete heart function tests, body-composition scans, fitness testing, or gastric emptying assessments. Researchers will compare glucose control, insulin needs, weight, metabolic markers, meal patterns, and patient-reported outcomes between groups, with the primary goal of determining whether glucose management without carbohydrate counting is not worse than (non-inferior to) standard carbohydrate counting.
The study also closely monitors safety, as tirzepatide can cause nausea, vomiting, diarrhea, decreased appetite, and rare complications such as gallbladder disease or pancreatitis. Overall, this research aims to learn whether combining tirzepatide with automated insulin delivery can safely simplify diabetes management, reduce treatment burden, and improve metabolic outcomes for adults living with type 1 diabetes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/m
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Tirzepatide group
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 counting for all meals. Beginning in Week 27, participants stop entering carbohydrate amounts into the pump (no meal announcements) for six weeks while continuing tirzepatide at their maintenance dose. Throughout the intervention, participants undergo regular safety assessments, remote glucose data reviews, insulin-pump parameter adjustments as needed, and scheduled in-person visits to monitor metabolic, cardiovascular, and patient-reported outcomes.
干预措施: Tirzepatide (Drug)
Tirzepatide group
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 counting for all meals. Beginning in Week 27, participants stop entering carbohydrate amounts into the pump (no meal announcements) for six weeks while continuing tirzepatide at their maintenance dose. Throughout the intervention, participants undergo regular safety assessments, remote glucose data reviews, insulin-pump parameter adjustments as needed, and scheduled in-person visits to monitor metabolic, cardiovascular, and patient-reported outcomes.
干预措施: Tandem Control-IQ Automated Insulin Delivery System (with Dexcom G7 CGM) (Device)
Tirzepatide group
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 counting for all meals. Beginning in Week 27, participants stop entering carbohydrate amounts into the pump (no meal announcements) for six weeks while continuing tirzepatide at their maintenance dose. Throughout the intervention, participants undergo regular safety assessments, remote glucose data reviews, insulin-pump parameter adjustments as needed, and scheduled in-person visits to monitor metabolic, cardiovascular, and patient-reported outcomes.
干预措施: Carbohydrate Counting (Behavioral)
Tirzepatide group
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 counting for all meals. Beginning in Week 27, participants stop entering carbohydrate amounts into the pump (no meal announcements) for six weeks while continuing tirzepatide at their maintenance dose. Throughout the intervention, participants undergo regular safety assessments, remote glucose data reviews, insulin-pump parameter adjustments as needed, and scheduled in-person visits to monitor metabolic, cardiovascular, and patient-reported outcomes.
干预措施: No Meal Announcement (Behavioral)
Control group
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, follow-up schedule, safety monitoring, glucose data reviews, and pump parameter adjustments as the tirzepatide arm. This arm serves as an active comparator, representing current standard therapy for type 1 diabetes with automated insulin delivery and meal announcements.
干预措施: Tandem Control-IQ Automated Insulin Delivery System (with Dexcom G7 CGM) (Device)
Control group
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, follow-up schedule, safety monitoring, glucose data reviews, and pump parameter adjustments as the tirzepatide arm. This arm serves as an active comparator, representing current standard therapy for type 1 diabetes with automated insulin delivery and meal announcements.
干预措施: Carbohydrate Counting (Behavioral)
结局指标
主要结局
Daytime Time-in-Range
时间窗: During the final 6 weeks of the study
The primary outcome is the percentage of daytime hours (06:00-24:00) during which participants' glucose levels, measured by the Dexcom G7 continuous glucose monitor, fall within the target range of 3.9-10.0 mmol/L.
次要结局
- Diastolic Blood Pressure(At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study.)
- Systolic Blood Pressure(At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study.)
- Echocardiogram (Diastolic Function Parameters)(At enrollment and at Week 32 (site-dependent).)
- Waist-to-Hip Ratio(At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study.)
- 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)
- Resting Heart Rate(At enrollment, Week 8, Week 16, Week 24, and Week 32, At Week 8 and Week 16 post-study.)
- Insulin-related measures(Continuously from randomization through Week 32, with primary analysis focused on Weeks 27-32, At Week 8 and Week 16 post-study.)
- Glucose outcomes(Continuously collected from randomization through Week 32, with key comparisons during Weeks 23-26 and Weeks 27-32, At Week 8 and Week 16 post-study.)
- Glycated Hemoglobin (HbA1c)(At enrollment, mid-study at Week 16, and at the end-of-study visit at Week 32, At Week 8 and Week 16 post-study.)
- Estimated Glomerular Filtration Rate(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Serum Creatinine(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Albumin-to-Creatinine Ratio(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Lipid Panel (Total Cholesterol, LDL-C, HDL-C, Triglycerides)(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Liver Function Markers (Alanine transaminase, Alkaline phosphatase)(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Liver Function Markers (Bilirubin)(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Cardiac Biomarkers (NT-proBNP)(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Inflammatory Biomarkers (hs-CRP)(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- Inflammatory Biomarkers (IL-6)(At enrollment, Week 16, and Week 32, At Week 8 and Week 16 post-study.)
- C-Peptide(At enrollment and at Week 32, At Week 8 and Week 16 post-study.)
- Carotid-Femoral Pulse Wave Velocity and Pulse Wave Analysis(At enrollment and at Week 32 (site-dependent).)
- DXA Body Composition(At enrollment and at Week 32 (site-dependent).)
- VO₂-max Test(At enrollment and at Week 32 (site-dependent).)
- Quality-of-Life Measures (Diabetes Distress Scale)(At enrollment and at Week 32.)
- Quality-of-Life Measures (Three Factor Eating r18 Questionnaire)(At enrollment and at Week 32.)
- Quality-of-Life Measures (Hypoglycemia Fear Survey II)(At enrollment and at Week 32.)
- Gastric Emptying via [13C] Acetate Breath Test(At enrollment (or training visit) and at Week 32 (site-dependent).)
- Blood Glucagon Response to Standardized Meal(At enrollment and at Week 32 (site-dependent).)
- Meal Tracking Using Keenoa or MyFood24(Prior to randomization, during Week 16, and during Week 32.)
研究者
Melissa-Rosina Pasqua
Assistant Professor, Division of Endocrinology and Metabolism
McGill University Health Centre/Research Institute of the McGill University Health Centre