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

Phase 4

Completed

Conditions: Type 2 Diabetes

Interventions: Drug: Tirzepatide
Drug: Dulaglutide

Registration Number: NCT05564039

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 282

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
15 Milligram (mg) Tirzepatide or Maximum Tolerated Dose (MTD)	Tirzepatide	Participants received tirzepatide administered as subcutaneous (SC) injection via a single-dose pen (SDP) once weekly (QW) for 40 weeks. The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks (2.5 mg to 5 mg to 7.5 mg to 10 mg to 12.5mg to 15 mg) until 15 mg or MTD was reached.
4.5 mg Dulaglutide or MTD	Dulaglutide	Participants received dulaglutide administered as SC injection via a SDP QW for 40 weeks. The starting dose of dulaglutide was either 1.5 mg QW, which increased by 1.5 mg every 4 weeks (1.5 mg to 3 mg to 4.5 mg) until 4.5 mg or MTD was reached, or 3.0 mg QW, which increased to 4.5 mg after 4 weeks or until MTD was reached.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c	Baseline, Week 40	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Body Weight	Baseline, Week 40	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.
Percentage of Participants Who Achieved HbA1c <7%	Week 40	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.
Percentage of Participants Who Achieved HbA1c <=6.5%	Week 40	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.
Percentage of Participants Who Achieved HbA1c <5.7%	Week 40	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.
Percentage of Participants Who Achieve Weight Loss From Baseline of ≥5%	Week 40	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.
Percentage of Participants Who Achieve Weight Loss From Baseline of ≥10%	Week 40	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.
Percentage of Participants Who Achieve Weight Loss From Baseline of ≥15%	Week 40	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.
Percentage of Participants Who Achieved Composite Endpoint (HbA1c <=6.5% & Weight Loss >=10% & No-Hypoglycemia)	Week 40	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.
Change From Baseline in Fasting Serum Glucose (FSG)	Baseline, Week 40	LSMean was calculated using the ANCOVA model for endpoint measures: Variable = Baseline + A1CGR1 + DULDSCRN + OAMGR1 + REGION1 + Treatment (Type I sum of squares).
Change From Baseline in Waist Circumference	Baseline, Week 40	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.
Change From Baseline in Body Mass Index (BMI)	Baseline, Week 40	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.
Change From Baseline in Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite CT) - Physical Functioning Score	Baseline, Week 40	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.'

Trial Locations

Locations (36): 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
Southern Endocrinology Associates
🇺🇸
Mesquite, Texas, United States
North Hills Family Medicine/North Hills Medical Research
🇺🇸
North Richland Hills, Texas, United States
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ALL Medical Research, LLC
🇺🇸Cooper City, Florida, United States