Diabetes Mellitus
Conditions
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. To compare efficacy of the triple combination therapy against standard therapy in achieving type 2 diabetes remission in patients newly diagnosed with T2DM. 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. Participants will: 1. Take new triple combination therapy or a standard therapy every day for 6 months 2. Visit the clinic once every 0.5-1 month for checkups and tests 3. Keep a diary of their fingertip blood glucose and adverse events
Interventions
DRUGGroup A (triple combination intensive therapy group)
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.
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years≤age≤75 years at the time of signing informed consent. 2. Newly diagnosed with type 2 diabetes, or diagnosed within 1 years according to the WHO diagnostic criteria. 3. 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. 4. 6.5%≤HbA1c≤9.0% at screening confirmed by central laboratory analysis. 5. BMI≥24 kg/m2.
Exclusion criteria
1. Individuals with type 1 diabetes or special types of diabetes. 2. Allergy or intolerance to investigational drugs. 3. Estimated Glomerular Filtration Rate (eGFR) \<20 mL/min/1.73 m². 4. Individuals with heart failure in New York Heart Association \[NYHA\] class III or IV in the 6 months prior to randomization. 5. History of bladder cancer or hematuria. 6. History of Multiple Endocrine Neoplasia Type 2 (MEN 2) or relevant family history. 7. History or family history of Medullary Thyroid Carcinoma (MTC), or susceptibility to MTC due to hereditary conditions. 8. History of fasting blood glucose≥13.9 mmol/L or the necessity for insulin use due to severe infection, diabetic foot, etc. 9. History of acute diabetic complications: including diabetic ketoacidosis, hyperglycemic hyperosmolar state, lactic acidosis. 10. Severe diabetic microvascular complications: proliferative retinopathy, or urinary AER\>300mg/g, or urinary protein positive, quantitative \>0.5g/24h. 11. Uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy. 12. 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. 13. Blood pressure persistently higher than 180/110 mmHg and not controllable to ≤160/100 mmHg within 1 week. 14. Alanine Aminotransferase (ALT) ≥2.5 times the upper normal limit, total bilirubin ≥1.5 times the upper normal limit. 15. Hemoglobin \<100g/L or requiring regular blood transfusion. 16. Use of medicines potentially affecting blood glucose for more than 1 week cumulatively in the past 12 weeks, such as corticosteroids, growth hormone analogs, estrogen/progestogen, high-dose diuretics, antipsychotic drugs, etc. 17. Participation in another trial involving medicine therapy within the past 3 months. 18. Expected lifespan less than 2 years as per the investigator's clinical judgment, e.g., but not limited to malignancy. 19. Pregnant or lactating females, or females of childbearing potential who cannot or are unwilling to use adequate contraception. 20. Deemed unsuitable for participation in this clinical trial at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diabetic remission rate | 6 months after discontinuation of medication | Diabetic remission rate at 6 months after discontinuation of medication (percentage of patients with HbA1c \<6.5% at 6 months after discontinuation of medication) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diabetic remission rate | 3 and 12 months after discontinuation of medication | Diabetic remission rate at 3 and 12 months after discontinuation of medication and the time of diabetic remission |
| Time required to achieve glycemic goal | 6 months of medication | The time required to achieve glycemic goal(FBG \<6.1mmol/L, 2h PPG \<8.0mmol/L or HbA1c#6.5%) |
| 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 | 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. |
| Incremental cost per additional remission | 6 months after discontinuation of medication | Incremental cost per additional remission at 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 | HbA1c level at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Blood glucose level | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | 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 |
| Blood insulin level | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | 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 |
| Blood C-peptide level | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | 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 |
| Pancreatic β-cell function | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | HOMA-B at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Insulin resistance | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | HOMA-IR at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Weight changes | At baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication | Weight at baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication |
| Time in range (TIR) | At baseline, at 6 months of medication treatment, and at 6 months after discontinuation of medication | Time within the target blood glucose range (3.9-10.0 mmol/L) |
| Incremental cost per additional improvement in Time in Range (TIR) | 6 months of medication treatment, and at 6 months after discontinuation of medication | Incremental cost per additional improvement in Time in Range (TIR) at 6 months of medication treatment, and at 6 months after discontinuation of medication |
| Incremental cost per QALY gained | At baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication | 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 |
Countries
China
Contacts
CONTACTHai Li, MD, PHD
Outcome results
None listed