Type 2 Diabetes
Conditions
Keywords
T2D, Diabetes
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.
Interventions
DRUGTirzepatide
Administered SC
As prescribed
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in Hemoglobin A1c (HbA1c) | Baseline, Week 104 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Weight | Baseline, Week 104 | — |
| Change from Baseline in Waist Circumference | Baseline, Week 104 | — |
| 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 | — |
| 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 | — |
| 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 HbA1c | Baseline, Week 208 | — |
| Change from Baseline in Weight loss of ≥5% | Baseline, Week 208 | — |
| A Composite Endpoint of HbA1c, Weight loss and Hypoglycemia | Week 104 | 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 |
| Change from Baseline in β-cell Glucose Sensitivity | Baseline, Week 104 | β-cell Glucose Sensitivity assessed by Oral Glucose Tolerance Test (OGTT) |
| Change from Baseline in β-cell glucose sensitivity | Baseline, Week 208 | Change from baseline in β-cell glucose sensitivity assessed by OGTT |
| Change from Baseline in Insulin Secretion Rate at a Fixed Glucose Concentration | Baseline, Week 104 | Insulin Secretion Rate assessed by OGTT |
| Change from Baseline in Postprandial Insulin Sensitivity Indices | Baseline, Week 104 | Postprandial Insulin Sensitivity Indices assessed by OGTT |
| Change from Baseline in Fasting and Post-challenge Glucose [total and incremental AUC(₀-₂₄₀min)] | Baseline through Week 104 | Fasting and Post-challenge Glucose \[total and incremental AUC(₀-₂₄₀min)\] assessed by OGTT |
| Change from Baseline in Fasting and Post-challenge Glucose [total and incremental (AUC₀-₂₄₀min)] | Baseline through Week 208 | Fasting and Post-challenge Glucose \[total and incremental AUC(₀-₂₄₀min)\] assessed by OGTT |
| 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 | — |
| Change from Baseline in Weight loss of ≥15% | Baseline, Week 104 | — |
Countries
Argentina, Canada, Germany, Israel, Italy, Mexico, Puerto Rico, Romania, Slovakia, United Kingdom, United States
Outcome results
None listed