Metformin plus SGLT‑2 inhibitor and GLP‑1 receptor agonist triple therapy for poorly controlled type 2 diabetes

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

This trial will see if adding an SGLT‑2 inhibitor and a GLP‑1 receptor agonist to metformin improves blood sugar control in adults with type 2 diabetes who have poor glycemic control.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 430 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07244003 on ClinicalTrials.gov

What this trial studies

This is a phase 4 interventional study comparing a triple combination of metformin, an SGLT‑2 inhibitor, and a GLP‑1 receptor agonist with other oral antidiabetic regimens in adults with type 2 diabetes and inadequate glycemic control. Eligible participants are adults (18–75 years) on at least 1000 mg metformin for ≥8 weeks with a centralized HbA1c between 7.5% and 11.0% and BMI ≥20 kg/m2. Those meeting criteria will receive either the triple therapy (examples include canagliflozin and liraglutide added to metformin) or comparator oral therapies and will be followed for efficacy and safety outcomes. The trial is sponsored by Hangzhou Zhongmei Huadong Pharmaceutical and conducted at Tianjin Medical University General Hospital.

Who should consider this trial

Good fit: Adults aged 18–75 with type 2 diabetes, BMI ≥20 kg/m2, on ≥1000 mg metformin for at least 8 weeks, and with HbA1c between 7.5% and 11.0% are ideal candidates.

Not a fit: People with type 1 diabetes, recent severe metabolic complications (like DKA), or recent use of GLP‑1RA or SGLT‑2 inhibitors are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, this regimen could help patients lower HbA1c and reduce weight while maintaining an acceptable safety profile when added to metformin.

How similar studies have performed: Previous trials have shown that SGLT‑2 inhibitors and GLP‑1 receptor agonists each improve glycemic control and weight, and some combination studies are favorable, but randomized data specifically on this exact triple combination remain limited.

Eligibility criteria

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.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical University General Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xiaofen Qian

Conditions T2DM