New Triple Therapy in Newly Diagnosed Type 2 Diabetes

NCT06946628 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: New Triple-2025
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn the efficany of combination therapy with semaglutide, empagliflozin and pioglitazone versus standard therapy in newly diagnosed type 2 diabetes. The main objectives to achieve are:

1. 1.To compare efficacy of the triple combination therapy against standard therapy in achieving type 2 diabetes remission in patients newly diagnosed with T2DM.
2. 2.To compare the effects on β-cell function and glycemic control of the triple combination therapy against standard therapy in patients newly diagnosed with T2DM
3. 3.Take new triple combination therapy or a standard therapy every day for 6 months
4. 4.Visit the clinic once every 0.5-1 month for checkups and tests
5. 5.Keep a diary of their fingertip blood glucose and adverse events

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Diabetic remission rate

  Diabetic remission rate at 6 months after discontinuation of medication (percentage of patients with HbA1c \<6.5% at 6 months after discontinuation of medication)

  6 months after discontinuation of medication

Secondary Outcomes (14)

• Diabetic remission rate

  3 and 12 months after discontinuation of medication

• Time required to achieve glycemic goal

  6 months of medication

• EQ-5D-5L questionnaires, quality of life

  At baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication

• Incremental cost per additional remission

  6 months after discontinuation of medication

• HbA1c

  baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication

Study Arms (2)

Group A (triple combination therapy group)

EXPERIMENTAL

semaglutide, empagliflozin, and pioglitazone treatment. 1) Initiate with Semaglutide 0.25 mg once weekly (qw) + Empagliflozin 10 mg once daily (qd) + Pioglitazone 15 mg once daily (qd); 2) After 1 month, if blood glucose is not controlled, adjust to Semaglutide 0.5 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd. If Semaglutide is well-tolerated, increase to 1 mg qw after 1 week; 3)If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.

Drug: Group A (triple combination therapy group)

Group B (standard therapy group)

ACTIVE COMPARATOR

metformin-based treatment is recommended when not contraindicated. 1).Initiate with Metformin monotherapy, titrate to the target dose of 1000 mg twice daily (bid) within 1 month or to the maximum tolerated dose (if Metformin is not tolerated, switch to Linagliptin 5 mg qd); 2) After 1 month, if blood glucose is not controlled, add a second antidiabetic drug, Empagliflozin 20 mg qd; 3) After another month, if blood glucose remains uncontrolled, add Semaglutide 0.25 mg qw, then increase to 0.5 mg qw after 1 month. If well-tolerated, increase to 1.0 mg qw after 1 week; 4) If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.

Drug: Group B (standard therapy group)

Interventions

Group A (triple combination therapy group) DRUG

1\) Initiate with Semaglutide 0.25 mg once weekly (qw) + Empagliflozin 10 mg once daily (qd) + Pioglitazone 15 mg once daily (qd); 2) After 1 month, if blood glucose is not controlled, adjust to Semaglutide 0.5 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd. If Semaglutide is well-tolerated, increase to 1 mg qw after 1 week; 3)If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.

Group A (triple combination therapy group)

Group B (standard therapy group) DRUG

metformin-based treatment is recommended when not contraindicated. 1).Initiate with Metformin monotherapy, titrate to the target dose of 1000 mg twice daily (bid) within 1 month or to the maximum tolerated dose (if Metformin is not tolerated, switch to Linagliptin 5 mg qd); 2) After 1 month, if blood glucose is not controlled, add a second antidiabetic drug, Empagliflozin 20 mg qd; 3) After another month, if blood glucose remains uncontrolled, add Semaglutide 0.25 mg qw, then increase to 0.5 mg qw after 1 month. If well-tolerated, increase to 1.0 mg qw after 1 week; 4) If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.

Group B (standard therapy group)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 years≤age≤75 years at the time of signing informed consent.
• Newly diagnosed with type 2 diabetes, or diagnosed within 1 years according to the WHO diagnostic criteria.
• Individuals who had not received previous antidiabetic therapy, or had not received antidiabetic therapy within 3 months prior to screening, or had not received antidiabetic therapy for more than 3 consecutive months or a combined total of more than 3 months in the past 2 years.
• %≤HbA1c≤9.0% at screening confirmed by central laboratory analysis.
• BMI≥24 kg/m2.

You may not qualify if:

• Individuals with type 1 diabetes or special types of diabetes.
• Allergy or intolerance to investigational drugs.
• Estimated Glomerular Filtration Rate (eGFR) \<20 mL/min/1.73 m².
• Individuals with heart failure in New York Heart Association \[NYHA\] class III or IV in the 6 months prior to randomization.
• History of bladder cancer or hematuria.
• History of Multiple Endocrine Neoplasia Type 2 (MEN 2) or relevant family history.
• History or family history of Medullary Thyroid Carcinoma (MTC), or susceptibility to MTC due to hereditary conditions.
• History of fasting blood glucose≥13.9 mmol/L or the necessity for insulin use due to severe infection, diabetic foot, etc.
• History of acute diabetic complications: including diabetic ketoacidosis, hyperglycemic hyperosmolar state, lactic acidosis.
• Severe diabetic microvascular complications: proliferative retinopathy, or urinary AER\>300mg/g, or urinary protein positive, quantitative \>0.5g/24h.
• Uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy.
• Severe diabetic macrovascular complications: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischemic attack and/or peripheral arterial disease required for vascular intervention or amputation within the 12 months prior to screening.
• Blood pressure persistently higher than 180/110 mmHg and not controllable to ≤160/100 mmHg within 1 week.
• Alanine Aminotransferase (ALT) ≥2.5 times the upper normal limit, total bilirubin ≥1.5 times the upper normal limit.
• Hemoglobin \<100g/L or requiring regular blood transfusion.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Hai Li, MD, PHD

CONTACT

+86-15920362668; lihai8@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Endocrinology Department

Model Details: Group A (triple combination therapy group): semaglutide, empagliflozin, and pioglitazone treatment. Group B (standard therapy group): metformin-based treatment is recommended when not contraindicated.

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: April 27, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)