A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4)

Lilly

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Insulin Glargine; Drug: Tirzepatide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03730662

17072

2018-002618-11 (EudraCT Number)

I8F-MC-GPGM (Other Identifier)

Details and patient eligibility

About

The purpose of the trial is to assess the efficacy and safety of tirzepatide taken once a week to insulin glargine taken once daily in participants with type 2 diabetes and increased cardiovascular risk. The study will last about 108 weeks and may include up to 30 visits.

Enrollment: 2,002 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Participants must:

• Have been diagnosed with type 2 diabetes mellitus (T2DM)
• Have HbA1c between ≥7.5% and ≤10.5%
• Be on stable treatment with unchanged dose of at least 1 and no more than 3 types of oral antihyperglycemic drugs, which may only include metformin, SGLT-2 inhibitors, and/or sulfonylureas for at least 3 months before screening
• Have increased risk for cardiovascular (CV) events
• Be of stable weight (± 5%)
• Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening

Exclusion Criteria

Participants must not:

• Have type 1 diabetes mellitus
• Have had chronic or acute pancreatitis any time prior to study entry
• Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment
• Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss
• Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level >3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range
• Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months
• Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
• Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 3 months
• Have been taking weight loss drugs, including over-the-counter medications during the last 3 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,002 participants in 4 patient groups

5 mg Tirzepatide

Experimental group

Description:

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Treatment:

Drug: Tirzepatide

10 mg Tirzepatide

Experimental group

Description:

10 mg tirzepatide administered SC once a week.

Treatment:

Drug: Tirzepatide

15 mg Tirzepatide

Experimental group

Description:

15 mg tirzepatide administered SC once a week.

Treatment:

Drug: Tirzepatide

Insulin Glargine

Active Comparator group

Description:

Insulin glargine administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin glargine was 10 IU/day at bedtime, titrated to a FBG \<100 mg/dL, following a treat-to-target (TTT) algorithm.

Treatment:

Drug: Insulin Glargine