A Study of Tirzepatide Compared With Intensified Conventional Care in Adult Participants With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
This study aims to investigate the efficacy and safety of tirzepatide in participants with type 2 diabetes (T2D) compared to other existing treatment options when treatment is initiated early.

Official Title
-----------------
A Randomized, Open-Label, Parallel-Group, Two-Arm, Phase 4 Study to Evaluate the Long-Term Efficacy and Safety of Tirzepatide Compared With Intensified Conventional Care in Adults When Initiating Treatment Early in the Course of Type 2 Diabetes

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Tirzepatide
* Drug: Antihyperglycemic medication


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have, within the last 4 years, been diagnosed with T2D based on the World Health Organization classification or other locally applicable diagnostic standards. Have HbA1c ≥7% to ≤9.5% as determined by the central laboratory. Have been on a stable treatment of metformin only at least 90 days preceding baseline with the minimum effective dose of ≥1500 mg/day, but not higher than the maximum approved dose per country-specific label, or <1500 mg/day in case of intolerance of full therapeutic dose. Exclusion Criteria: Have type 1 diabetes mellitus Have a history of chronic or acute pancreatitis any time prior to study entry Have a history of proliferative diabetic retinopathy diabetic macular edema, or no proliferative diabetic retinopathy requiring immediate or urgent treatment Are at high risk for cardiovascular disease (CVD) in the investigator's opinion or have a history of any of these CV conditions prior to study entry myocardial infarction percutaneous coronary revascularization procedure carotid stenting or surgical revascularization nontraumatic amputation peripheral vascular procedure (e.g., stenting or surgical revascularization) cerebrovascular accident (stroke), or congestive heart failure Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2) Have within 90 days prior to screening received treatment with medications intended to promote weight loss. This includes prescribed, over the counter, or alternative remedies Have an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 (or lower than the country-specific threshold for discontinuing metformin therapy per local label), calculated by chronic kidney disease-epidemiology equation as determined by central laboratory at screening. Have been treated with any injectable glucagon-like peptide-1 (GLP-1) receptor agonists and insulin prior to screening. Exception: use of insulin for gestational diabetes or short-term use (<14 days) for acute conditions such as acute illness, hospitalization, or elective surgery.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide<br>Participants will receive tirzepatide at the maximum tolerated dose subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Active Comparator: Intensified Conventional Care Dose<br>Participants will receive an antihyperglycemic medication | Drug: Antihyperglycemic medication<br>* As prescribed<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Hemoglobin A1c (HbA1c) |  | Baseline, Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HbA1c |  | Baseline, Week 208 | 
| Change from Baseline in Weight |  | Baseline, Week 104 | 
| Change from Baseline in Weight |  | Baseline, Week 208 | 
| Change from Baseline in Waist Circumference |  | Baseline, Week 104 | 
| Change from Baseline in Waist Circumference |  | Baseline, Week 208 | 
| Change from Baseline in Fasting Serum Glucose (FSG) |  | Baseline, Week 104 | 
| Change from Baseline in FSG |  | Baseline, Week 208 | 
| Change from Baseline in Lipids |  | Baseline, Week 104 | 
| Change from Baseline in Lipids |  | Baseline, Week 208 | 
| Percentage of Participants Achieving HbA1c <7.0% |  | Week 104 | 
| Percentage of Participants Achieving HbA1c ≤6.5% |  | Week 104 | 
| Percentage of Participants Achieving HbA1c <5.7% |  | Week 104 | 
| Percentage of Participants Achieving HbA1c <7.0% |  | Week 208 | 
| Percentage of Participants Achieving HbA1c ≤6.5% |  | Week 208 | 
| Percentage of Participants Achieving HbA1c <5.7% |  | Week 208 | 
| Change from Baseline in Weight loss of ≥5%, |  | Baseline, Week 104 | 
| Change from Baseline in Weight loss of ≥10% |  | Baseline, Week 104 | 
| Change from Baseline in Weight loss of ≥15% |  | Baseline, Week 104 | 
| Change from Baseline in Weight loss of ≥5% |  | Baseline, Week 208 | 
| Change from Baseline in Weight loss of ≥10% |  | Baseline, Week 208 | 
| Change from Baseline in Weight loss of ≥15% |  | Baseline, Week 208 | 
| A Composite Endpoint of HbA1c, Weight loss and Hypoglycemia | A composite endpoint defined as HbA1c ≤ 6.5%, weight loss ≥10%, no hypoglycemia, defined as blood glucose (BG) <54 milligram/deciliter (mg/dL) <3.0 millimole/liter (mmol/L) and/or severe hypoglycemia | Week 104 | 
| A Composite Endpoint of HbA1c, Weight loss and Hypoglycemia | A composite endpoint defined as HbA1c ≤ 6.5%, weight loss ≥10%, no hypoglycemia, defined as BG <54 mg/dL (<3.0 mmol/L) and/or severe hypoglycemia | Week 208 | 
| Change from Baseline in β-cell Glucose Sensitivity | β-cell Glucose Sensitivity assessed by Oral Glucose Tolerance Test (OGTT) | Baseline, Week 104 | 
| Change from Baseline in β-cell glucose sensitivity | Change from baseline in β-cell glucose sensitivity assessed by OGTT | Baseline, Week 208 | 
| Change from Baseline in Insulin Secretion Rate at a Fixed Glucose Concentration | Insulin Secretion Rate assessed by OGTT | Baseline, Week 104 | 
| Change from Baseline in Insulin Secretion Rate at a Fixed Glucose Concentration | Insulin Secretion Rate assessed by OGTT | Baseline, Week 208 | 
| Change from Baseline in Postprandial Insulin Sensitivity Indices | Postprandial Insulin Sensitivity Indices assessed by OGTT | Baseline, Week 104 | 
| Change from Baseline in Postprandial Insulin Sensitivity Indices | Postprandial Insulin Sensitivity Indices assessed by OGTT | Baseline, Week 208 | 
| Change from Baseline in Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)] | Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)] assessed by OGTT | Baseline through Week 104 | 
| Change from Baseline in Fasting and Post-challenge Glucose [total and incremental (AUC₀-₂₄₀min)] | Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)] assessed by OGTT | Baseline through Week 208 | 
| Change from Baseline in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) - Physical Functioning Domain |  | Baseline, Week 104 | 
| Change from Baseline in the IWQOL-Lite-CT - Physical Functioning Domain |  | Baseline, Week 208 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, T2D