A Study of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes Mellitus (AWARD-10)

Lilly

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Dulaglutide; Drug: Metformin; Drug: SGLT2 inhibitor; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02597049

15361

H9X-MC-GBGE (Other Identifier)

2015-002095-24 (EudraCT Number)

Details and patient eligibility

About

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as dulaglutide when added to sodium-glucose co-transporter 2 (SGLT2) inhibitors in participants with type 2 diabetes mellitus.

Enrollment: 424 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have type 2 diabetes mellitus (based on the World Health Organization's [WHO] diagnostic criteria)

• Have been treated with an SGLT2 inhibitor, with or without metformin, for at least 3 months prior to study entry (minimum required doses for that period for allowed SGLT2 inhibitors: empagliflozin 10 mg, dapagliflozin 5 or 10 mg [per country-specific label], canagliflozin 100 mg); minimum required dose for metformin, if used, is ≥1500 mg/day and must be reached (or highest tolerated dose which is acceptable with documented gastrointestinal [GI] intolerability)

• Daily doses of all allowed oral antihyperglycemia agent (OAMs) must have been stable for at least 12 weeks (±3 days) prior to randomization (study enrollment); daily doses of SGLT2 inhibitor and metformin, if used, will be considered stable during this period if:

  • all prescribed daily doses were in the range between the minimum required dose and maximum-approved dose per country-specific label; and
  • >90% of prescribed daily doses were equal to the dose at randomization

• Have HbA1c ≥7.0% and ≤9.5% at study entry and approximately 1 week prior to randomization

• Have body mass index (BMI) ≤45 kilograms per meter squared (kg/m^2) and agree to not initiate a diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment

Exclusion criteria

• Have type 1 diabetes mellitus
• Have been treated with any other OAMs (other than SGLT2 inhibitors and metformin), glucagon-like peptide-1 receptor agonist (GLP-1 RA), pramlintide or insulin 3 months prior to study entry, or between study entry and randomization; or initiate metformin between study entry and randomization; short-term use of insulin for acute care (≤14 days) during the 3-month period prior to entry is not exclusionary
• Have any condition that is a contraindication for use of the GLP-1 RA class or the SGLT2 inhibitor class (per country-specific labels) at study entry or develop such condition between study entry and randomization
• Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine transaminase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial
• Had chronic or acute pancreatitis any time prior to study entry
• Estimated glomerular filtration rate (eGFR) <45 milliliters(mL)/minute/1.73m^2, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory at study entry and confirmed at lead in
• Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia (this exclusion includes participants with a family history of MEN 2A or 2B, whose family history for the syndrome is rearranged during transfect [RET]-negative; the only exception for this exclusion will be for participants whose family members with MEN 2A or 2B have a known RET mutation and the potential participant for the study is negative for the RET mutation)
• Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome)
• Have a serum calcitonin ≥20 picograms/mL as determined by the central laboratory at study entry

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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424 participants in 3 patient groups, including a placebo group

1.5 mg Dulaglutide

Experimental group

Description:

1.5 milligrams (mg) given subcutaneously (SC) once a week for 24 weeks.

Treatment:

Drug: SGLT2 inhibitor

Drug: Dulaglutide

Drug: Metformin

0.75 mg Dulaglutide

Experimental group

Description:

0.75 mg dulaglutide given SC once a week for 24 weeks.

Treatment:

Drug: SGLT2 inhibitor

Drug: Dulaglutide

Drug: Metformin

Placebo

Placebo Comparator group

Description:

Placebo given SC once a week for 24 weeks.

Treatment:

Drug: SGLT2 inhibitor

Drug: Metformin

Drug: Placebo