A Study of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dulaglutide; Placebo; SGLT2 inhibitor; Metformin
Intervention description: Administered SC; Administered SC; Administered orally as standard of care for type 2 diabetes; Administered orally as standard of care for type 2 diabetes
Intervention MeSH terms: Metformin; Dapagliflozin; Empagliflozin; Canagliflozin; Dulaglutide; Sodium-Glucose Transporter 2 Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 424.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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