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

November 5, 2026 updated by: Linong Ji, Peking University People's Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
182

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥18 years at screening.

  2. Patients with a clinical diagnosis of T1D for at least 12 months.

    Patients with T1D must satisfy all three of the following features:

    1. Clinical diagnosis of type 1 diabetes by a specialist physician;
    2. 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;
    3. 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).

  3. Willingness to use once-weekly mazdutide.

  4. HbA1c ≥7.0% and <10.0%.

  5. Body mass index (BMI) ≥20 kg/m².

  6. 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:

    1. Multiple daily injections of basal insulin plus prandial insulin;
    2. Premixed insulin analog injected 2-3 times daily;
    3. Dual insulin analog (insulin degludec/aspart) injected twice daily;
    4. 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].

  7. 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: ***

1. 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.

3. Carotid atherosclerotic plaque confirmed by ultrasound.

Exclusion Criteria:

  1. Other types of diabetes.
  2. BMI <20 kg/m².
  3. History of cardiovascular disease: previous myocardial infarction, unstable angina, coronary revascularization (PCI or CABG), stroke, transient ischemic attack (TIA), or symptomatic peripheral arterial disease.
  4. Renal impairment: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (based on the CKD-EPI equation).
  5. Hepatic disease: known severe hepatic disease, or ALT/AST levels >3 times the upper limit of normal.
  6. Personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2.
  7. Pancreatic disease: history of acute or chronic pancreatitis.
  8. Pregnancy and lactation: women who are pregnant, breastfeeding, or planning pregnancy and unwilling to use effective contraception.
  9. 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.
  10. Requirement for long-term use of systemic glucocorticoids (topical/inhaled use permitted).
  11. History of hypersensitivity to GLP-1 receptor agonists, mazdutide, or any of its excipients.
  12. Moderate or more severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy.
  13. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: mazdutide group

Participants in the treatment group will receive mazdutide by subcutaneous injection once weekly. The dose will be escalated stepwise according to a pre-defined regimen from a safe starting dose to an effective maintenance dose (from 2 mg to 4 mg) over several weeks, with dose reduction permitted if needed.
Drug: Mazdutide

Mazdutide is a synthetic peptide analog of mammalian oxyntomodulin and a once-weekly dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR), under development for the treatment of obesity and type 2 diabetes (T2D). Mazdutide has been shown to induce significant weight loss in patients with obesity and to help improve glycemic control in patients with T2D.
Placebo Comparator: placebo group

Participants in the control group will receive a placebo matched to mazdutide in appearance, packaging, and mode of administration, by subcutaneous injection once weekly.
Drug: Placbo

mazdutide matching placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of the participants achieving time in range (TIR)>70 and time below range (TBR)<4% (TIMES-EFFICACY)
Time Frame: From baseline to 16 weeks

The proportion of adult patients with T1D achieving the composite outcome of continuous glucose monitoring (CGM)-measured TIR >70% and TBR <4% at Week 16 in the mazdutide group versus the placebo group
From baseline to 16 weeks
Volume of non-calcified coronary artery plaque (TIMES-CV)
Time Frame: From baseline to 52 weeks

The absolute change in non-calcified coronary artery plaque volume in mm³ from baseline to Week 52, as measured by quantitative analysis of high-resolution coronary computed tomography angiography (CCTA)
From baseline to 52 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Level of HbA1c
Time Frame: From baseline to 52 weeks

Changes in HbA1c (%) from baseline to Week 16 and Week 52
From baseline to 52 weeks
Volume of coronary atherosclerotic plaque
Time Frame: From baseline to 52 weeks

Changes in total coronary atherosclerotic plaque volume, fibrous plaque volume, low-density plaque volume, and lipid-rich plaque volume in mm³
From baseline to 52 weeks
Thickness of carotid intima-media
Time Frame: From baseline to 52 weeks

Changes in carotid intima-media thickness (cIMT) in mm from baseline to Week 52
From baseline to 52 weeks
Time in range (TIR)
Time Frame: From baseline to 52 weeks

Changes in TIR (%) from baseline to Week 52
From baseline to 52 weeks
Time above range (TAR)
Time Frame: From baseline to 52 weeks

Changes in TAR (%) from the baseline to Week 52
From baseline to 52 weeks
Time below range (TBR)
Time Frame: From baseline to 52 weeks

Changes in TBR (%) from baseline to Week 52
From baseline to 52 weeks
Covariation (CV)
Time Frame: From baseline to 52 weeks

Changes in CV (%) assessed by continuous glucose monitoring from baseline to Week 52
From baseline to 52 weeks
Level of triglyceride (TG)
Time Frame: From baseline to 52 weeks

Changes in TG (mmol/L) from baseline to Week 52
From baseline to 52 weeks
Level of total cholesterol (TC)
Time Frame: From baseline to 52 weeks

Changes in TC (mmol/L) from baseline to Week 52
From baseline to 52 weeks
Level of low-density cholesterol (LDL-C)
Time Frame: From baseline to 52 weeks

Changes in LDL-C (mmol/L) from baseline to Week 52
From baseline to 52 weeks
Level of high-density cholesterol (HDL-C)
Time Frame: From baseline to 52 weeks

Changes in HDL-C (mmol/L) from baseline to Week 52
From baseline to 52 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The level of urinary albumin/creatinine ratio
Time Frame: From baseline to 52 weeks

Changes in urinary albumin/creatinine ratio (mg/g) from baseline to Week 52
From baseline to 52 weeks
Change in hepatic fat content
Time Frame: From baseline to 52 weeks

Changes in hepatic fat content (%) from baseline to Week 52, assessed by MRI-PDFF
From baseline to 52 weeks
Levels of inflammation-related protein biomarkers
Time Frame: From baseline to Week 52

Changes in inflammation-related protein biomarkers (assessed by Olink) from baseline to Week 52
From baseline to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University People's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Qilu Hospital of Shandong University
Hebei General Hospital
Zhongnan Hospital
The First Affiliated Hospital of Henan University of Science and Technology
Shenzhen Second People's Hospital
Second Affiliated Hospital of Soochow University
Tianjin Medical University
Second Xiangya Hospital of Central South University
Heji Hospital affiliated to Changzhi Medical College
Tangshan Worker's Hospital
The Second Hospital of Shijiazhuang

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2027

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 20, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2026PHD024-004
  • 3-SRA-2026-1955-M-B (Other Grant/Funding Number: Breakthrough T1D)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make individual participant data (IPD) collected in this study available to researchers outside the primary research group. The study data will be kept confidential by the sponsor and investigators in accordance with applicable regulations and the study protocol. Sharing of IPD is not planned due to considerations regarding participant confidentiality and data protection.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings