A Randomized, Double-Blind Trial Comparing the Effect of Dulaglutide 1.5 mg With Placebo on Glycemic Control in Patients With Type 2 Diabetes on Basal Insulin Glargine
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 300
- Locations
- 20
- Primary Endpoint
- Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)
Study Overview
Brief Summary
The main purpose of this study is to evaluate the use of the study drug known as dulaglutide in participants with type II diabetes who are taking once-daily insulin glargine. The study will last about 31 weeks for each participant.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have type 2 diabetes (based on the World Health Organization's [WHO] diagnostic criteria)
- •Have been treated with basal insulin glargine once daily with or without metformin for at least 3 months prior to screening
- •Doses of once daily insulin glargine and metformin (if taken) must be stable during the 3-month period prior to screening. Doses of metformin are considered stable if all prescribed doses during this period are in the range between the minimum required dose (≥1500 mg/day) and the maximum approved dose per the locally-approved label
- •Have an HbA1c value ≥7.0% and ≤10.5% as assessed by the central laboratory at screening
- •Require further insulin glargine dose increase at week 3 per the treat-to-target (TTT) algorithm based on the SMPG data collected during the prior week
- •Have stable weight (±5%) ≥3 months prior to screening
- •Have body mass index (BMI) ≤45 kilograms per square meter (kg/m^2) at screening
- •Are able and willing to administer once weekly randomized therapy
- •Are females of childbearing potential who must:
- •Test negative for pregnancy at screening, based on a serum pregnancy test
- •Agree to use a reliable method of birth control
- •Not be breastfeeding
Exclusion Criteria
- •Have been treated with ANY other antihyperglycemia regimen, other than basal insulin glargine once daily with or without metformin, within the 3 months prior to screening or between screening and week 3
- •Have a history of ≥1 episode of ketoacidosis or hyperosmolar state/coma
- •Have a history of hypoglycemia unawareness within the 6 months prior to screening
- •Have been treated with drugs that promote weight loss within the 3 months prior to screening or between screening and week 3
- •Are receiving chronic (>14 days) systemic glucocorticoid therapy or have received such therapy within the 4 weeks prior to screening or between screening and week 3
- •Have had any of the following cardiovascular conditions within the 2 months prior to screening: acute myocardial infarction (MI), New York Heart Association (NYHA) Class III or Class IV heart failure, or cerebrovascular accident (stroke)
- •Have a known clinically significant gastric emptying abnormality or have undergone gastric bypass surgery or restrictive bariatric surgery
- •Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory
- •Have a history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis within the 3 months prior to screening
- •Have an estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 square meter (mL/min/m^2), calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory; for participants on metformin, have renal disease or renal dysfunction (for example, a serum creatinine ≥1.5 mg/deciliter [dL] [male] or ≥1.4 mg/dL [female] or eGFR [CKD-EPI] <60 mL/min/1.73 m^2)
- •Have evidence of a significant, uncontrolled endocrine abnormality
- •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
- •Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome)
- •Have serum calcitonin ≥20 picograms/mL, as determined by the central laboratory
- •Have evidence of a significant, active autoimmune abnormality
- •Have any other condition not listed in this section that is a contraindication for use of insulin glargine, or, for participants using metformin, have a condition that is a contraindication for the use of metformin and would require metformin discontinuation per label
- •Have a history of transplanted organ
- •Have a history of active or untreated malignancy, or are in remission from a clinically significant malignancy during the 5 years prior to screening
- •Have a history of any other condition which, in the opinion of the investigator, may preclude the participants from following and completing the protocol
- •Have any hematologic condition that may interfere with HbA1c measurement (eg, hemolytic anemias, sickle-cell disease)
Arms & Interventions
Dulaglutide + Insulin Glargine
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Intervention: Dulaglutide (Drug)
Dulaglutide + Insulin Glargine
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Intervention: Insulin Glargine (Drug)
Dulaglutide + Insulin Glargine
1.5 milligrams (mg) dulaglutide administered subcutaneously (SQ) once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Intervention: Metformin (Drug)
Placebo + Insulin Glargine
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Intervention: Placebo (Drug)
Placebo + Insulin Glargine
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Intervention: Insulin Glargine (Drug)
Placebo + Insulin Glargine
Placebo administered SQ once weekly for 28 weeks. Titrated insulin glargine administered SQ once daily for 28 weeks. Participants who are taking metformin should remain on stable doses.
Intervention: Metformin (Drug)
Outcomes
Primary Outcomes
Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)
Time Frame: Baseline, 28 Weeks
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least-squares (LS) mean and standard error (SE) changes from baseline in HbA1c at 28 weeks were measured using mixed model regression and restricted maximum likelihood (REML) with treatment, pooled country, visit, and treatment-by -visit interaction as fixed effects, baseline as covariate, and participant as a random effect.
Secondary Outcomes
- Change From Baseline to 28 Weeks in Body Weight(Baseline, 28 Weeks)
- Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose(Baseline, 28 Weeks)
- Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)(Baseline, 28 Weeks)
- Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events(Baseline through 28 Weeks)
- Percentage of Participants Discontinuing the Study Due to Severe, Persistent Hyperglycemia(Baseline through 28 Weeks)
- Number of Participants With Dulaglutide Anti-Drug Antibodies(Baseline, Week 12 and Week 28)
- Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%(28 Weeks)
- Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 Kilograms [kg]) at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)(28 Weeks)
- Percentage of Participants Achieving HbA1c Target of <7.0% at 28 Weeks and Without Documented Symptomatic Hypoglycemia During the Maintenance Period (Weeks 12-28)(28 Weeks)
- Percentage of Participants Achieving HbA1c Target of <7.0% and Without Weight Gain (<0.1 kg)(28 Weeks)
- Change From Baseline to 28 Weeks in 7-Point Self Monitored Plasma Glucose (SMPG)(Baseline, 28 Weeks)
- Percentage of Participants With Self-Reported Events of Hypoglycemia(Baseline through 28 Weeks)
- Number of Participants With Adjudicated Acute Pancreatitis Events(Baseline through 28 Weeks)
- Number of Participants With Thyroid Tumors/Neoplasms (Including C-Cell Hyperplasia)(Baseline through 28 Weeks)
- Rate of Hypoglycemic Events up to 28 Weeks(Baseline through 28 Weeks)