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

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Drug: LY2189265
Drug: Insulin glargine
Drug: Sulfonylureas (SU)
Drug: Biguanide (BG)
Registration Number
NCT01584232
Lead Sponsor
Eli Lilly and Company
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
361
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)
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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)
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LY2189265 + OAMLY2189265LY2189265: 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).
Insulin glargine + OAMSulfonylureas (SU)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).
Insulin glargine + OAMBiguanide (BG)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).
LY2189265 + OAMSulfonylureas (SU)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).
LY2189265 + OAMBiguanide (BG)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).
Insulin glargine + OAMInsulin glargineInsulin 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).
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 WeeksBaseline, 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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieved Glycosylated Hemoglobin (HbA1c) <=6.5% or <7% at 26 WeeksUp to 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.

Change From Baseline in Fasting Blood Glucose (FBG) at 26 WeeksBaseline, 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.

Change From Baseline in 8-Point Self-Monitored Blood Glucose (SMBG) at 26 WeeksBaseline, Up to 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.

Change From Baseline in Body Weight at 26 WeeksBaseline, 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.

Percentage of Participants With Hypoglycemic EpisodesBaseline through 26 Weeks

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.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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Yamaguchi, Japan

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