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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:
Participants will:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Diabetic remission rate | Diabetic remission rate at 3 and 12 months after discontinuation of medication and the time of diabetic remission | 3 and 12 months after discontinuation of medication |
| Time required to achieve glycemic goal |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hai Li, MD, PHD | Contact | +86-15920362668 | lihai8@mail.sysu.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Sun Yat-sen University | Guangzhou | Guangdong | 510080 | China |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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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.
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| 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. |
|
The time required to achieve glycemic goal(FBG <6.1mmol/L, 2h PPG <8.0mmol/L or HbA1c#6.5%)
| 6 months of medication |
| EQ-5D-5L questionnaires, quality of life | EQ-5D-5L questionnaires, assessment of quality of life. The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement. | At baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication |
| Incremental cost per additional remission | Incremental cost per additional remission at 6 months after discontinuation of medication | 6 months after discontinuation of medication |
| HbA1c | HbA1c level at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Blood glucose level | Fasting and 2-hour postprandial blood glucose level at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Blood insulin level | Fasting and 2-hour postprandial insulin level at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Blood C-peptide level | Fasting and 2-hour postprandial C-peptide level at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Pancreatic β-cell function | HOMA-B at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Insulin resistance | HOMA-IR at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Weight changes | Weight at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Time in range (TIR) | Time within the target blood glucose range (3.9-10.0 mmol/L) | At baseline, at 6 months of medication treatment, and at 6 months after discontinuation of medication |
| Incremental cost per additional improvement in Time in Range (TIR) | Incremental cost per additional improvement in Time in Range (TIR) at 6 months of medication treatment, and at 6 months after discontinuation of medication | 6 months of medication treatment, and at 6 months after discontinuation of medication |
| Incremental cost per QALY gained | Incremental cost per QALY gained, derived from EQ-5D-5L assessments at baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication | At baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication |