Efficacy and Safety of the Met+SGLT-2i+GLP-1RA in Patients With Type 2 Diabetes With Poor Glycemic Control (MESSAGE)

Efficacy and Safety of the Triple Combination Therapy of Met/SGLT-2i/GLP-1RA or Other Oral Antidiabetic Drugs in Patients With Type 2 Diabetes Exhibiting Poor Glycemic Control

The main objective of this study is to compare the efficacy and safety of the triple combination therapy of Met/SGLT-2i/GLP-1RA or other oral antidiabetic drugs in patients with type 2 diabetes exhibiting poor glycemic control.

Study Overview

• Status: Recruiting
• Conditions: T2DM (Type 2 Diabetes Mellitus)
• Intervention / Treatment: Drug: Metformin; Drug: ganagliflozin; Drug: liraglutide; Drug: Triple Therapy of Other Oral Antidiabetic Drugs

• Study Type: Interventional
• Enrollment (Estimated): 430
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiaofen Qian; Phone Number: +86-0571-89908582; Email: qianxiaofen@eastchinapharm.com
• Study Contact Backup: Name: Wanting Zhang; Phone Number: +86-0571-89905517; Email: zhangwanting@eastchinapharm.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Recruiting
      • Tianjin Medical University General Hospital
      • Contact: Ming Liu; Phone Number: +86 183 2201 7516; Email: mingliu@tmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Meet the diagnostic criteria for type 2 diabetes (refer to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 edition)); -Age: 18-75 years old (including the threshold), male or female;
• Body mass index (BMI) ≥20kg/m² ;
• Patients who took 1000mg or more of metformin in combination with or without another oral hypoglycemic agent (except SGLT-2i and oral GLP-1RA) for at least 8 weeks before screening and had poor blood glucose control (centralized detection of HBA1C >=7.5% and<=11.0%);
• Volunteer to participate in this study and sign informed consent.

Exclusion Criteria:

• Patients with type 1 diabetes or other special types of diabetes;
• Patients with acute complications of ketoacidosis/hyperglycemic hyperosmolar state/lactic acidosis within 6 months before screening
• Those who have used GLP-1RA and SGLT-2i drugs within 12 weeks before screening, or have used GLP-1RA and SGLT-2i drugs in the past and discontinued due to poor efficacy
• Those who received insulin treatment within the previous week
• Those who have a history of chronic or acute pancreatitis before screening, or have clinical manifestations of pancreatitis at the time of screening, or fasting triglycerides > 5.7 mmol/L during the screening period
• Liver function impairment at screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 UNL, or total blood bilirubin (TBIL) > 2 UNL;
• Renal impairment at screening: calculated according to the CKD-EPI formula, eGFR≤45 mL/min/1.73m² or serum creatinine≥1.5 UNL;
• Patients with a past or family history of medullary thyroid cancer (MTC) and patients with multiple endocrine neoplasia syndrome type 2 (MEN2)
• Female subjects who are currently pregnant, breastfeeding, or have a pregnancy plan during the study period
• Those who have a history of hypersensitivity reaction to metformin, gapagliflozin, liraglutide injection and other drugs used in research and their excipients or have contraindications to the study drugs;
• Those who have participated in other drug clinical trials within 3 months before screening; 21. Subjects who are unable to comply with the protocol under the judgment of the investigator, and those who have other serious physical or psychological diseases that may affect the effectiveness and safety.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Met+SGLT-2i+GLP-1RA; Metformin+Ganagliflozin+Liraglutide	Drug: Metformin; The dosage of metformin hydrochloride was consistent with baseline.; Drug: ganagliflozin; Ganagliflozin tablet : 50mg/d.; Drug: liraglutide; Liraglutide injection: 0.6 mg/d for the first week, 1.2 mg/d for the second week, and 1.8 mg/d after the third week.
Active Comparator: Triple Therapy of Other Oral Antidiabetic Drugs; Building upon the previously stable treatment regimen, the addition of 1-2 oral hypoglycemic agents (excluding SGLT-2 inhibitors and oral GLP-1 receptor agonists) constitutes a triple oral hypoglycemic regimen.	Drug: Triple Therapy of Other Oral Antidiabetic Drugs; The dosage of metformin hydrochloride was consistent with baseline. The usage and dosage of other hypoglycemic drugs were referred to their respective instructions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change of HbA1c compared to the baseline	from baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants achieving HbA1c, blood pressure, and cholesterol targets	HbA1c ≤ 7.0% Blood pressure < 130/80 mmHg For subjects without ASCVD, LDL-C < 2.6 mmol/L; for subjects with ASCVD, LDL-C < 1.8 mmol/L (< 70 mg/dL)	week 24
The proportion of patients achieving HbA1c target without hypoglycemia or weight gainning	HbA1c target ≤ 7.0% The definition of hypoglycemia is: Blood glucose < 70 mg/dL ( < 3.9 mmol/L), regardless of whether there are symptoms of hypoglycemia.	week 24
The changes of waist circumference and hip circumference compared to the baseline		from baseline to week 24
The changes of fasting blood glucose, 2-hour post-meal blood glucose, fasting glucagon, fasting insulin, insulin resistance index (HOMA-IR) compared to the baseline		from baseline to week 24
Changes in systolic and diastolic blood pressure compared to the baseline		from baseline to week 24
The changes in urine albumin-to-creatinine ratio (UACR) compared to the baseline		from baseline to week 24
The changes of body mass compared to the baseline		from baseline to 24 week
The changes of BMI compared to the baseline		from baseline to 24 week
The changes of waist-hip ratio, waist-to-height ratio compared to the baseline		from baseline to 24 week

Other Outcome Measures

Outcome Measure	Time Frame
The changes in total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate aminotransferase compared to the baseline	from baseline to week 120
The proportion of participants who received rescue treatment	from baseline to week 24

Collaborators and Investigators

• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Biguanides; Guanidines; Amidines; Gastrointestinal Hormones; Glucagon-Like Peptides; Proglucagon; Glucagon-Like Peptide 1; Liraglutide; Metformin
• Other Study ID Numbers: HD-LLPHYJ-LC-1

Drug and device information, study documents

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