A Study of Dulaglutide (LY2189265) in Participants With Type II Diabetes

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Placebo
Drug: Dulaglutide
Drug: Insulin Glargine
Drug: Metformin

Registration Number: NCT02152371

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 300

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Insulin Glargine	Placebo	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.
Dulaglutide + Insulin Glargine	Dulaglutide	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.
Dulaglutide + Insulin Glargine	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.
Placebo + Insulin Glargine	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.
Placebo + Insulin Glargine	Metformin	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.
Dulaglutide + Insulin Glargine	Metformin	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to 28 Weeks in Hemoglobin A1c (HbA1c)	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 Outcome Measures

Name	Time	Method
Change From Baseline to 28 Weeks in Body Weight	Baseline, 28 Weeks	LS means of the body weight change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline body weight as covariate, via a MMRM analysis.
Change From Baseline to 28 Weeks in Daily Mean Insulin Glargine Dose	Baseline, 28 Weeks	Least Square (LS) Means of the insulin dose change from baseline to primary endpoint at week 28 was adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline insulin dose as covariate, via a MMRM analysis.
Change From Baseline to 28 Weeks in Fasting Serum Glucose (FSG)	Baseline, 28 Weeks	FSG is a test to determine glucose levels after an overnight fast. LS means FSG change from baseline to primary endpoint at week 28 was calculated using a mixed effects model for repeated measures (MMRM) analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline FSG as covariate.
Number of Participants With Investigator Reported and Adjudicated Cardiovascular Events	Baseline through 28 Weeks	Cardiovascular (CV) adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the sponsor. Deaths occurring during the study treatment period and nonfatal CV AEs were to be adjudicated. Nonfatal CV events that were to be adjudicated were myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (CVA/stroke), and transient ischemic attack (TIA).
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	Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 12 and 28. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Percentage of Participants Achieving HbA1c Targets of <7.0% or ≤6.5%	28 Weeks	Percentage of participants who achieved HbA1c levels of \<7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.
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 who achieved a target HbA1c target of \<7%, without weight gain and without documented symptomatic hypoglycemia at 28 weeks were analyzed using regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.
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 target HbA1c of \<7.0% at 28 weeks without documented symptomatic hypoglycemia are presented. Documented symptomatic hypoglycemia is defined as any time a participant experienced symptoms and or signs associated with hypoglycemia and had a plasma glucose of \<=70 mg/dL.
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	The LS means of the 7-point SMPG change from baseline to primary endpoint at week 28 was measured using a MMRM analysis adjusted by treatment, country, metformin use, week, treatment-by-week interaction, and baseline SMPG as covariate.
Percentage of Participants With Self-Reported Events of Hypoglycemia	Baseline through 28 Weeks	Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The percentage of participants with self-reported hypoglycemic events is presented.
Number of Participants With Adjudicated Acute Pancreatitis Events	Baseline through 28 Weeks	The number of cases of acute pancreatitis confirmed by adjudication. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
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	The rate of total hypoglycemic events any type per 30 days is presented. The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period\*30 days.

Trial Locations

Locations (20): Valley Endocrine, Fresno
🇺🇸
Fresno, California, United States
Northwest Endo Diabetes Research, LLC
🇺🇸
Arlington Heights, Illinois, United States
Mills-Peninsula Diabetes Research Insitute
🇺🇸
San Mateo, California, United States
Cotton O'Neil Clinic
🇺🇸
Topeka, Kansas, United States
Bland Clinic, PA
🇺🇸
Greensboro, North Carolina, United States
Rainier Clinical Research Center
🇺🇸
Renton, Washington, United States
Centro de Endocrinologia y Nutricion del Turabo
🇵🇷
Caguas, Puerto Rico
Ponce School of Medicine CAIMED Center
🇵🇷
Ponce, Puerto Rico
University Clinical Investigators, Inc.
🇺🇸
Tustin, California, United States
AB Clinical Trials
🇺🇸
Las Vegas, Nevada, United States
Polyclinic
🇺🇸
Seattle, Washington, United States
GCM Medical Group PSC
🇵🇷
San Juan, Puerto Rico
American Telemedicine Center
🇵🇷
San Juan, Puerto Rico
SHS Clinical Research Group
🇺🇸
Toms River, New Jersey, United States
Endocrine Lipid Diabetes Research Institute
🇵🇷
Ponce, Puerto Rico
Manati Center for Clinical Research Inc
🇵🇷
Manati, Puerto Rico
PMG Research of Knoxville
🇺🇸
Knoxville, Tennessee, United States
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸
Idaho Falls, Idaho, United States
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.
🇬🇧
Swansea, Wales, United Kingdom
Kentucky Diabetes Endocrinology Center
🇺🇸
Lexington, Kentucky, United States