A Study of Dulaglutide in Japanese Participants With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this trial is to examine the efficacy and safety of once-weekly LY2189265 (dulaglutide) in participants with type 2 diabetes mellitus taking an oral antihyperglycemic medication (OAM).

Detailed Description
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Rescue therapy (defined as alternative antihyperglycemic medication use or dose modification of oral antihyperglycemic medication [OAM]) may have been initiated during the planned treatment period if the participant discontinued study drug or met prespecified thresholds for severe, persistent hyperglycemia. Efficacy data, as well as data for hypoglycemic episodes from participants who permanently discontinued study treatment but switched to another diabetes medication and remained in the study, were censored from the point of initiating new treatment onwards.

Official Title
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A Phase 3 Study of LY2189265 Compared to Insulin Glargine in Patients With Type 2 Diabetes Mellitus on a Sulfonylurea and/or Biguanide

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LY2189265
* Drug: Insulin glargine
* Drug: Sulfonylureas (SU)
* Drug: Biguanide (BG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have had a diagnosis of type 2 diabetes mellitus for at least 6 months before screening Participants who have been taking sulfonylurea (glibenclamide, gliclazide, or glimepiride) and/or biguanide (metformin or buformin). The dose of the drug(s) during the 8 weeks before screening must be stable Participants who have a qualifying glycosylated hemoglobin (HbA1c) value of 7.0% to 10.0% at screening Participants who have a body mass index (BMI) of 18.5 to 35.0 kilograms per meter squared (kg/m^2) Exclusion Criteria: Participants who have a diagnosis of type 1 diabetes Participants who have previously been treated with any other glucagon-like peptide 1 (GLP-1) analog Participants who have received therapy with an alpha-glucosidase inhibitor (a-GI), thiazolidinedione (TZD), glinide, or dipeptidyl peptidase-IV (DPP-IV) inhibitor within 3 months before screening Participants who have been currently taking insulin or have had previous insulin treatment within 3 months before screening Participants who have obvious clinical signs or symptoms of pancreatitis, a history of chronic pancreatitis, or acute pancreatitis at screening, as determined by the investigator. Participants who have a serum amylase concentration ≥ 3 times the upper limit of the reference range and/or a serum lipase concentration ≥ 2 times the upper limit of the reference range, as determined by the central laboratory at screening Participants who have self or family history of medullary C-cell hyperplasia, focal hyperplasia, or medullary thyroid carcinoma (MTC)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2189265 + OAM<br>LY2189265: 0.75 milligrams (mg), administered subcutaneously (SC), once weekly for 26 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of oral antihyperglycemic medication (OAM) throughout the study. OAMs included sulfonylureas (SU; glibenclamide, gliclazide, or glimepiride) and/or biguanides (BG; metformin or buformin). | Drug: LY2189265<br> <br> * Other names: Dulaglutide;Drug: Sulfonylureas (SU)<br> <br> Drug: Biguanide (BG)<br> <br> |
| Active Comparator: Insulin glargine + OAM<br>Insulin glargine: dose based on targeting fasting blood glucose ≤110 milligrams per deciliter (mg/dL), administered subcutaneously (SC), once daily for 26 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of oral antihyperglycemic medication (OAM) throughout the study. OAMs included sulfonylureas (SU; glibenclamide, gliclazide, or glimepiride) and/or biguanides (BG; metformin or buformin). | Drug: Insulin glargine<br> <br> Drug: Sulfonylureas (SU)<br> <br> Drug: Biguanide (BG)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks | Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect. | Baseline, 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Glycosylated Hemoglobin (HbA1c) <=6.5% or <7% at 26 Weeks | The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a longitudinal logistic regression model with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect. | Up to 26 weeks | 
| Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks | Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline FBG as a covariate, and participant as a random effect. | Baseline, 26 weeks | 
| Change From Baseline in 8-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks | Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal, at bedtime, and before breakfast the next morning (second pre-morning meal). Least squares (LS) means were calculated using analysis of covariance (ANCOVA) model with treatment, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects and baseline SMBG as a covariate. | Baseline, Up to 26 weeks | 
| Change From Baseline in Body Weight at 26 Weeks | Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, oral antihyperglycemic medication regimen (sulfonylureas only, biguanides only, or both), and baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline body weight as a covariate, and participant as a random effect. | Baseline, 26 weeks | 
| Percentage of Participants With Hypoglycemic Episodes | The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least one hypoglycemic episode over the 26-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Baseline through 26 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucagon-like peptide-1 (GLP-1)