New Triple Combination Therapy in Newly Diagnosed Type 2 Diabetes

NCT07635953 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: R21002
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn the efficacy of combination therapy with tirzepatide, 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 Researchers will compare drug new triple combination therapy with tirzepatide, empagliflozin, and pioglitazone to standard therapy (metformin based treatment) to see if new triple combination therapy works better in achieving type 2 diabetes remission.
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

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

Study Arms (2)

Group A (triple combination intensive therapy group)

EXPERIMENTAL

Tirzepatide, empagliflozin, and pioglitazone treatment. 1) Initiate with Tirzepatide 2.5 mg once weekly (qw) + Empagliflozin 10 mg once daily (qd) + Pioglitazone 15 mg once daily (qd); 2) After 1 month, adjust Tirzepatide to 5.0 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd; 3) After 1 month, adjust Tirzepatide to 7.5 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd. 4) After 1 month, adjust Tirzepatide to 10.0 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd; 5) If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.

Drug: Group A (triple combination intensive 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 1 month, if blood glucose remains uncontrolled, add Tirzepatide 2.5 mg qw; 4) After 1 month, if blood glucose remains uncontrolled, adjust Tirzepatide to 5.0 mg qw; 5) After 1 month, if blood glucose remains uncontrolled, adjust Tirzepatide to 7.5 mg qw; 6) After 1 month, if blood glucose remains uncontrolled, adjust Tirzepatide to 10.0 mg qw.

Drug: Group B (standard therapy group)

Interventions

Group B (standard therapy group) DRUG

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 1 month, if blood glucose remains uncontrolled, add Tirzepatide 2.5 mg qw; 4) After 1 month, if blood glucose remains uncontrolled, adjust Tirzepatide to 5.0 mg qw; 5) After 1 month, if blood glucose remains uncontrolled, adjust Tirzepatide to 7.5 mg qw; 6) After 1 month, if blood glucose remains uncontrolled, adjust Tirzepatide to 10.0 mg qw.

Group B (standard therapy group)

Group A (triple combination intensive therapy group) DRUG

1\) Initiate with Tirzepatide 2.5 mg once weekly (qw) + Empagliflozin 10 mg once daily (qd) + Pioglitazone 15 mg once daily (qd); 2) After 1 month, adjust Tirzepatide to 5.0 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd; 3) After 1 month, adjust Tirzepatide to 7.5 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd. 4) After 1 month, adjust Tirzepatide to 10.0 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd; 5) If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.

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

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: June 9, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2031
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)