A Study of HDM1005 in Participants With T2DM Not Controlled With Metformin Alone or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

A Multicenter, Randomized, Open-label, Parallel-controlled, Phase 3 Study to Compare the Efficacy and Safety of HDM1005 Versus Mazdutide in Subjects With T2DM Inadequate Glycemic Control by Metformin Monotherapy or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

This study is a multicenter, randomized, open-label, parallel-group, phase 3 clinical trial aimed at evaluating the efficacy and safety of HDM1005 versus active comparator in subjects with Type 2 Diabetes Mellitus (T2DM) Inadequate Glycemic Control by Metformin Monotherapy or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor.

A total of 912 subjects will be enrolled. All subjects will be stratified by baseline HbA1c levels (≤8.5% or >8.5%) and metformin monotherapy (yes or no), then randomized 1:1:1 to: Group 1 (HDM1005), Group 2 (HDM1005), and Group 3 (active comparator), with 304 subjects in each treatment group. All treatment groups will implement dose titration to achieve the target dose.

The study consists of: up to 2-week screening, 2-week run-in, 40-week core treatment, 12-week extension treatment, and 4-week follow-up, totaling 60 weeks. The end-of-study visit will be conducted 28 days after the last administration cycle.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: HDM1005 1; Drug: HDM1005 2; Drug: Mazdutide

• Study Type: Interventional
• Enrollment (Estimated): 912
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jiaying Li; Phone Number: +86 19157709998; Email: lijiaying@eastchinapharm.com

Study Locations

• China
  • Beijing, China
    • Peking University People's Hospital
    • Contact: Linong Ji; Phone Number: +86 13910978815; Email: jiln@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Confirmed as Type 2 Diabetes Mellitus (T2DM) for at least 12 weeks and on a stable dosage of metformin alone or in combination with an SGLT2 inhibitor for at least 12 weeks prior to screening.
2. Hemoglobin A1c (HbA1c) ≥7.5% and ≤11.0% (local laboratory) at screening; and ≥7.0% and ≤11.0% (central laboratory) at randomization.
3. Body Mass Index (BMI) ≥22.5 kg/m2.

Exclusion Criteria:

1. Other types of diabetes besides T2DM.
2. Acute complications of diabetes (such as diabetic ketoacidosis, diabetic lactic acidosis, or hyperosmolar non-ketotic coma) occurred within 24 weeks prior to signing the Informed Consent Form (ICF).
3. History of a level 3 hypoglycemic episode or a history of asymptomatic hyp oglycemic episodes within 24 weeks prior to signing the ICF.
4. History or family history of medullary thyroid carcinoma (MTC), thyroid C-cell hyperplasia, or multiple endocrine neoplasia type 2 (MEN2).
5. History of acute or chronic pancreatitis; or presence of risk factors for pancreatitis; or history of symptomatic gallbladder disease requiring treatment per investigator's assessment within 24 weeks prior to signing the ICF.
6. Investigator determines that the subject has a condition or disease affecting gastric emptying or gastrointestinal nutrient absorption, such as weight-loss surgery or other gastric resections, irritable bowel syndrome, dyspepsia, or gastroparesis.
7. Use of antidiabetic medications within 12 weeks prior to signing the ICF, with the exception of metformin monotherapy or combination therapy with an SGLT2 inhibitor; excluding short-term insulin use (cumulative duration ≤7 days) for concomitant illness, stress, or perioperative periods.
8. Hemoglobin (Hb) <100 g/L (female) or <110 g/L (male).
9. FPG ≥13.9 mmol/L.
10. Aspartate aminotransferase (AST) >3× upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3× ULN.
11. Total bilirubin >1.5× ULN.
12. Fasting triglyceride (TG) >5.6 mmol/L (500 mg/dL).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group: HDM1005 1; HDM1005 administered subcutaneously (SC)	Drug: HDM1005 1; administered SC, QW, 52 week
Experimental: Experimental group: HDM1005 2; HDM1005 administered SC	Drug: HDM1005 2; administered SC, QW, 52 week
Active Comparator: Active Comparator: Mazdutide; Mazdutide administered SC	Drug: Mazdutide; administered SC, QW, 52 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.	Baseline, Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in HbA1c	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time	Baseline, Week 52
The percentage of patients reaching the HbA1c targets of <7.0%, ≤6.5%, and <5.7%	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time	Week 40, Week 52
Change from baseline in fasting plasma glucose (FPG)	FPG is a test to determine sugar levels in serum sample after an overnight fast	Baseline, Week 40, Week 52
Change from baseline in body weight	Change from baseline in body weight is calculated by subtracting the baseline weight measurement from the post-treatment weight measurement at a specified time point	Baseline, Week 40, Week 52

Collaborators and Investigators

• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.
• Investigators: Study Director: Linong Ji, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 27, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; mazdutide
• Other Study ID Numbers: HDM1005-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No