A Study of Tirzepatide (LY3298176) in Adult Participants With Type 2 Diabetes Switching From Dulaglutide (SURPASS-SWITCH)

Eli Lilly and Company282 enrolled

Overview

The main purpose of this study is to investigate the efficacy and safety of switching from weekly dulaglutide to weekly tirzepatide compared to increasing the dulaglutide dose in adults with type 2 diabetes.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

282

Conditions

Type 2 Diabetes

Interventions

TirzepatideDRUG

Administered SC

DulaglutideDRUG

Administered SC

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Have type 2 diabetes * Have HbA1c ≥7.0% (≥53 mmol/mol) to ≤9.5% (≤80 mmol/mol) * Are currently on a stable dose of dulaglutide weekly (0.75 mg or 1.5 mg) for at least 6 months prior to screening. * No treatment with oral antihyperglycemic medication (OAM), or on a stable dose of up to 3 OAMs, which may include metformin, sodium glucose cotransporter-2 inhibitors (SGLT-2i), and/or sulfonylurea, for at least 3 months before screening. * Have had stable body weight (±5%) during the 90 days preceding screening * Have BMI ≥25 kilogram/square meter (kg/m²) Exclusion Criteria: * Have type 1 diabetes * Have a history of chronic or acute pancreatitis * Have a history of * proliferative diabetic retinopathy, or * diabetic maculopathy, or * nonproliferative diabetic retinopathy that requires acute treatment. * Have any of these cardiovascular (CV) conditions within 60 days prior to screening: * acute myocardial infarction, * cerebrovascular accident (stroke), or * hospitalization due to congestive heart failure (CHF). * Have New York Heart Assocation (NYHA) Functional Classification Class IV CHF * 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) * Have been treated with 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. * Have a history of reduction of dose of dulaglutide, due to intolerability, without successful reescalation

Locations (38)

Outcomes

Primary Outcomes

Change From Baseline in HbA1c

HbA1c is the glycated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + Number of Background OAMs Group 1 + Dulaglutide Dose at Screening + Geographic Region 1 + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.

Time frame: Baseline, Week 40

Secondary Outcomes

Change From Baseline in Body Weight

LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Number of Background OAMs Group 1 + Dulaglutide Dose at Screening + Geographic Region 1 + Baseline HbA1c Group + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.

Time frame: Baseline, Week 40

Percentage of Participants Who Achieved HbA1c <7%

The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline HbA1c Value, Baseline SGLT2i use(Yes/No), Treatment, Visit, and Treatment by Visit interaction.

Time frame: Week 40

Percentage of Participants Who Achieved HbA1c <=6.5%

The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable. Logistic regression model was used with missing endpoint measures imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for baseline HbA1c, geographic region 1, number of background OAMs in group 1, dulaglutide dose at screening, and treatment as factors.

Data from ClinicalTrials.gov

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ALL Medical Research, LLC

Cooper City, Florida, United States

Metabolic Research Institute, Inc.

West Palm Beach, Florida, United States

NorthShore University Health System

Skokie, Illinois, United States

Iowa Diabetes and Endocrinology Research Center

West Des Moines, Iowa, United States

Clinvest Research LLC

Springfield, Missouri, United States

Alliance for Multispecialty Research, LLC

Norman, Oklahoma, United States

Juno Research

Houston, Texas, United States

Biopharma Informatic, LLC

Houston, Texas, United States

Juno Research

Houston, Texas, United States

Southern Endocrinology Associates

Mesquite, Texas, United States

...and 28 more locations

Percentage of Participants Who Achieved HbA1c <5.7%

The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Analyses included all participants having non-missing baseline and at least one non-missing post-baseline value of the response variable. Logistic regression model was used with missing endpoint measures imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for baseline HbA1c, geographic region 1, number of background OAMs in group 1, dulaglutide dose at screening, and treatment as factors.

Time frame: Week 40

Percentage of Participants Who Achieve Weight Loss From Baseline of ≥5%

Missing endpoint measures are imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures: Variable = Baseline + Geographic Region 1 + Number of Background OAMs Group 1 + Dulaglutide Dose at Screening + Baseline HBA1C Group + Treatment + Time + Treatment\*Time.

Time frame: Week 40

Percentage of Participants Who Achieve Weight Loss From Baseline of ≥10%

Time frame: Week 40

Percentage of Participants Who Achieve Weight Loss From Baseline of ≥15%

Time frame: Week 40

Percentage of Participants Who Achieved Composite Endpoint (HbA1c <=6.5% & Weight Loss >=10% & No-Hypoglycemia)

A composite endpoint is defined as HbA1c ≤ 6.5%, weight loss ≥ 10%, and no hypoglycemia, defined as blood glucose (BG) \<3.0 millimole/liter (mmol/L) and/or severe hypoglycemia. Missing endpoint measures are imputed by predictions using observed data in the efficacy analysis set from the same treatment group through an MMRM analysis model for post-baseline measures: For HbA1c: Variable = Baseline + Geographic Region 1 + Number of Background OAMs Group 1 + Dulaglutide Dose at Screening + Treatment + Time + Treatment\*Time. For Weight: Variable = Baseline + Geographic Region 1 + Number of Background OAMs Group 1 + Dulaglutide Dose at Screening + Baseline HbA1c Group + Treatment + Time + Treatment\*Time.

Time frame: Week 40

Change From Baseline in Fasting Serum Glucose (FSG)

LSMean was calculated using the ANCOVA model for endpoint measures: Variable = Baseline + A1CGR1 + DULDSCRN + OAMGR1 + REGION1 + Treatment (Type I sum of squares).

Time frame: Baseline, Week 40

Change From Baseline in Waist Circumference

Time frame: Baseline, Week 40

Change From Baseline in Body Mass Index (BMI)

Change from Baseline in BMI is presented. LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Number of Background OAMs Group 1 + Dulaglutide Dose at Screening + Geographic Region 1 + Baseline HbA1c Group + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.

Time frame: Baseline, Week 40

Change From Baseline in Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite CT) - Physical Functioning Score

The IWQOL-Lite-CT is a 20-item, obesity-specific PRO (patient-reported outcome) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items, where 5 of the items comprise the physical functioning sub-domain) and psychosocial (13 items). The IWQOL-Lite-CT provides composite scores for each domain, as well as a total score, all ranging from 0 to 100. Higher scores reflect better levels of functioning. This endpoint shows results for 'physical function domain.'

Time frame: Baseline, Week 40