Efficacy, Safety and Cardiovascular Protection of Mazdutide in Type 1 Diabetes

Trial details

Who runs it

Peking University People's Hospital

Trial code

NCT07924553

Record updated

2026. november 9.

Original description

This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial in patients with type 1 diabetes (T1D), conducted in two stages.Read full original descriptionShow less

Type 1 Diabetes Intervention With Mazdutide for Efficacy, Safety and Cardiovascular Protection (The TIMES Trial Program-TIMES-EFFICACY & TIMES-CV

This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial in patients with type 1 diabetes (T1D), conducted in two stages.

Stage 1 is the efficacy and safety assessment (TIMES-EFFICACY). A total of 182 T1D patients who meet the inclusion criteria will be randomized in a 1:1 ratio to two groups: one receiving mazdutide and the other receiving placebo. The follow-up period is 16 weeks. The primary clinical endpoint is the proportion of patients achieving time in range (TIR) >70% with time below range (TBR) <4%. An interim analysis will be performed at Week 8; if the absolute TBR in the mazdutide group increases by more than 5% relative to the placebo group, the subsequent study will be terminated.

Stage 2 is the cardiovascular protective effect assessment (TIMES-CV). During the Stage 1 efficacy and safety assessment, a pre-specified stratification method will ensure that 104 patients with high cardiovascular risk factors are randomized in a 1:1 ratio to the mazdutide group or the placebo group. After completing the 16-week efficacy and safety assessment, these 104 subjects will continue to receive randomized controlled treatment and enter the cardiovascular effect assessment stage, with a total follow-up duration of 52 weeks. The primary clinical endpoint is the change in non-calcified coronary artery plaque volume.

Inclusion: Age ≥18 years at screening; Patients with a clinical diagnosis of T1D for at least 12 months; Patients with T1D must satisfy all three of the following features:; Clinical diagnosis of type 1 diabetes by a specialist physician; Any one of the following: age at onset <15 years; no overweight or obesity at onset; diabetic ketoacidosis at onset; peak stimulated C-peptide <200 pmol/L; Any one of the following: continuous insulin therapy since diagnosis (excluding pancreas or islet transplantation); one or more positive pancreatic islet autoantibodies (GADA / IAA / IA-2A / ZnT8); Willingness to use once-weekly mazdutide; HbA1c ≥7.0% and <10.0%; Body mass index (BMI) ≥20 kg/m²; Continuous use of any of the following insulin regimens for at least 3 months prior to screening (no concomitant use of other oral glucose-lowering drugs or GLP-1RAs allowed), with a stable insulin dose for at least 2 weeks before enrollment:; Multiple daily injections of basal insulin plus prandial insulin; Premixed insulin analog injected 2-3 times daily; Dual insulin analog (insulin degludec/aspart) injected twice daily; Continuous subcutaneous insulin infusion (CSII). Note: A stable insulin dose is defined as a daily insulin dose adjustment of no more than ±[value not specified in the source document]; Ability to provide informed consent prior to any study-related activity; For participants enrolled in TIMES-CV, in addition to the above criteria, the following criteria must also be met: ***; Duration of type 1 diabetes ≥5 years. 2. Moderate or high 10-year atherosclerotic cardiovascular disease (ASCVD) risk (≥5.0%) as assessed by the China-PAR model; Carotid atherosclerotic plaque confirmed by ultrasound.

Exclusion: History of cardiovascular disease: previous myocardial infarction, unstable angina, coronary revascularization (PCI or CABG), stroke, transient ischemic attack (TIA), or symptomatic peripheral arterial disease; Other types of diabetes; Personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2; Pancreatic disease: history of acute or chronic pancreatitis; History of hypersensitivity to GLP-1 receptor agonists, mazdutide, or any of its excipients; Any other serious medical or psychiatric condition that, in the judgment of the investigator, may interfere with study assessments or endanger the safety of the subject; Renal impairment: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (based on the CKD-EPI equation); Hepatic disease: known severe hepatic disease, or ALT/AST levels >3 times the upper limit of normal; Medications: use of GLP-1 receptor agonists, GIP or GCG receptor agonists, other non-insulin glucose-lowering drugs, or finerenone within 3 months prior to screening; BMI <20 kg/m²; Pregnancy and lactation: women who are pregnant, breastfeeding, or planning pregnancy and unwilling to use effective contraception; Requirement for long-term use of systemic glucocorticoids (topical/inhaled use permitted); Moderate or more severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy.

ClinicalTrials.gov NCT07924553