Clinical trial NCT01648582: A Study Comparing the Effects and Safety of Dulaglutide With Insulin Glargine in Type 2 Diabetes Mellitus
Official title: The Efficacy and Safety of Once-Weekly, Subcutaneous Dulaglutide Compared to Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Mellitus on Metformin and/or a Sulfonylurea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-07-24
Enrollment: 774
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine if once-weekly dulaglutide is efficient and safe compared to once-daily insulin glargine in participants with type 2 diabetes mellitus who have inadequate glycemic control with 1 or 2 oral antihyperglycemic medications (OAM) (metformin and/or a sulfonylurea), in addition to any healthy lifestyle changes recommended by their healthcare providers.


Eligibility criteria: Inclusion Criteria:

* Have type 2 diabetes mellitus for at least 6 months
* Have been taking metformin and/or a sulfonylurea for at least 3 months before screening and have been on a stable therapeutic dose for at least 8 weeks
* Glycosylated hemoglobin (HbA1c) value of ≥7.0% to ≤11.0%
* Adult men or adult non-pregnant, non-breastfeeding women
* Body Mass Index (BMI) of ≥19.0 to ≤35.0 kilograms/square meter (kg/m\^2)
* Stable weight (±5%) ≥3 months prior to screening

Exclusion Criteria:

* Have type 1 diabetes mellitus
* Have previous treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, GLP-1 analog, or any other incretin mimetic
* Have treatment with dipeptidyl peptidase-IV (DPP-IV) inhibitor, an alpha-glucosidase inhibitor (AGI), thiazolidinedione (TZD), or glinide
* Have gastric emptying abnormality
* Have cardiac disorder defined as unstable angina, myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, heart failure, arrhythmia, transient ischemic attack, or stroke
* Have poorly controlled hypertension (systolic blood pressure above 160 millimeter of mercury\[mmHg\] or diastolic blood pressure above 95 mmHg)
* Have impaired liver function
* Have impaired kidney function
* Have history of chronic pancreatitis or acute pancreatitis
* Have a serum calcitonin ≥20 picograms per milliliter (pg/mL)
* Have a personal or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma, or multiple endocrine neoplasia type 2 (MEN 2)

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks
timeFrame: Baseline, 26 Weeks
Secondary outcomes:
measure: Change From Baseline in HbA1c at 52 Weeks
timeFrame: Baseline, 52 Weeks
measure: Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks
timeFrame: Up to 26 and 52 weeks
measure: Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 weeks, 52 weeks
measure: Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weeks
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Rate of Hypoglycemic Events
timeFrame: Baseline through 26 weeks and 52 weeks
measure: Number of Self-reported Hypoglycemic Events
timeFrame: Baseline through 26 Weeks and 52 Weeks
measure: Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP)
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR)
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in Pancreatic Enzymes
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in Serum Calcitonin
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Number of Participants With Adjudicated Cardiovascular (CV) Events
timeFrame: Baseline through 52 weeks
measure: Number of Participants With Adjudicated Pancreatitis
timeFrame: Baseline through 52 Weeks
measure: Change From Baseline in Body Weight
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change in Body Mass Index
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA)
timeFrame: Baseline through 52 Weeks
measure: EQ-5D Health State Score Responses
timeFrame: Baseline, 26 Weeks, 52 Weeks
measure: Change From Baseline in EQ-5D Visual Analog Scale Score
timeFrame: Baseline, 26 weeks, 52 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: 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.
city: Changsha
country: China
facility: 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.
city: Chengdu
country: China
facility: 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.
city: Chongqing
country: China
facility: 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.
city: Dalian
country: China
facility: 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.
city: Guang Zhou
country: China
facility: 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.
city: Guiyang
country: China
facility: 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.
city: Hangzhou
country: China
facility: 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.
city: Harbin
country: China
facility: 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.
city: Hefei
country: China
facility: 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.
city: Nanchang
country: China
facility: 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.
city: Nanjing
country: China
facility: 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.
city: Nanning
country: China
facility: 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.
city: Shanghai
country: China
facility: 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.
city: Shenyang
country: China
facility: 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.
city: Shijiazhuang
country: China
facility: 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.
city: Wu Han
country: China
facility: 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.
city: Xi'An
country: China
facility: 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.
city: Yangzhou
country: China
facility: 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.
city: Zhenjiang
country: China
facility: 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.
city: Bucheon,
country: Korea, Republic of
facility: 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.
city: Kyunggi-Do
country: Korea, Republic of
facility: 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.
city: Seoul
country: Korea, Republic of
facility: 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.
city: Wonju-Si
country: Korea, Republic of
facility: 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.
city: Chihuahua
country: Mexico
facility: 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.
city: Monterrey
country: Mexico
facility: 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.
city: Chelyabinsk
country: Russian Federation
facility: 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.
city: Moscow
country: Russian Federation
facility: 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.
city: Saint Petersburg
country: Russian Federation
facility: 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.
city: Sankt-Petersburg
country: Russian Federation
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Cai TT, Li HQ, Jiang LL, Wang HY, Luo MH, Su XF, Ma JH. Effects of GLP-1 Receptor Agonists on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: A 52-Week Clinical Study. Biomed Res Int. 2021 Sep 17;2021:3361309. doi: 10.1155/2021/3361309. eCollection 2021.
citation: Zhou Y, Zhu J, Wu H, Deng Y, Ji Q. Pancreatic Safety of Once-Weekly Dulaglutide in Chinese Patients with Type 2 Diabetes Mellitus: Subgroup Analysis by Potential Influencing Factors. Diabetes Ther. 2021 Oct;12(10):2677-2690. doi: 10.1007/s13300-021-01139-2. Epub 2021 Aug 28.
citation: Ma J, Zhang B, Hou J, Peng Y. Efficacy and Safety of Once Weekly Dulaglutide in East Asian Patients with Type 2 Diabetes: Subgroup Analysis by Potential Influential Factors. Diabetes Ther. 2021 Jan;12(1):211-222. doi: 10.1007/s13300-020-00955-2. Epub 2020 Nov 8.
citation: Kuang J, Zhu J, Liu S, Li Q. Efficacy and Safety of Once-Weekly Dulaglutide in Elderly Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN Studies. Diabetes Ther. 2020 Oct;11(10):2329-2339. doi: 10.1007/s13300-020-00910-1. Epub 2020 Aug 28.
citation: Guo L, Zhang B, Hou J, Zhou Z. Evaluation of Characteristics of Gastrointestinal Adverse Events with Once-Weekly Dulaglutide Treatment in Chinese Patients with Type 2 Diabetes: A Post Hoc Pooled Analysis of Two Randomized Trials. Diabetes Ther. 2020 Aug;11(8):1821-1833. doi: 10.1007/s13300-020-00869-z. Epub 2020 Jul 4.
citation: Yu M, Yuan GY, Zhang B, Wu HY, Lv XF. Efficacy and Safety of Dulaglutide by Baseline HbA1c in Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis. Diabetes Ther. 2020 May;11(5):1147-1159. doi: 10.1007/s13300-020-00804-2. Epub 2020 Apr 10.
citation: Wang J, Li HQ, Xu XH, Kong XC, Sun R, Jing T, Ye L, Su XF, Ma JH. The Effects of Once-Weekly Dulaglutide and Insulin Glargine on Glucose Fluctuation in Poorly Oral-Antidiabetic Controlled Patients with Type 2 Diabetes Mellitus. Biomed Res Int. 2019 Dec 24;2019:2682657. doi: 10.1155/2019/2682657. eCollection 2019.
citation: Li Y, Li L, De Peng Y, Song GY, Ye SD, Du LY, Hou JN, Ji QH. Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2). Diabetes Ther. 2019 Aug;10(4):1435-1452. doi: 10.1007/s13300-019-0646-y. Epub 2019 Jun 21.