A Study Comparing the Effects and Safety of Dulaglutide With Insulin Glargine in Type 2 Diabetes Mellitus

NCT01648582 | Completed Phase 3 Results DMC

• 2 other identifiers: 13439H9X-CR-GBDK
• Study Type: interventional
• Target: 774
• Locations: 4 countries
• Sites: 30

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks

  HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) means of change from baseline in HbA1c were calculated using a mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, baseline HbA1c, country, oral antihyperglycemic medication (OAM) , visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect.

  Baseline, 26 Weeks

Secondary Outcomes (21)

• Change From Baseline in HbA1c at 52 Weeks

  Baseline, 52 Weeks

• Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks

  Up to 26 and 52 weeks

• Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks

  Baseline, 26 Weeks, 52 Weeks

• Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks

  Baseline, 26 Weeks, 52 Weeks

• Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks

  Baseline, 26 weeks, 52 weeks

Study Arms (3)

1.5 mg Dulaglutide

EXPERIMENTAL

1.5 milligrams (mg) dulaglutide administered as one subcutaneous (SC) injection once-weekly added to participant's pre-study prescribed dose of metformin and/or a sulfonylurea for up to 52 weeks. Participants are blinded to the dulaglutide dose.

Drug: Dulaglutide; Drug: Metformin; Drug: Sulfonylureas

0.75 mg Dulaglutide

EXPERIMENTAL

0.75 mg Dulaglutide administered as one SC injection once-weekly added to participant's pre-study prescribed dose of metformin and/or a sulfonylurea for up to 52 weeks. Participants are blinded to the dulaglutide dose.

Drug: Dulaglutide; Drug: Metformin; Drug: Sulfonylureas

Insulin Glargine

ACTIVE COMPARATOR

Insulin glargine administered based on fasting blood glucose concentrations per the dosing titration schedule as once daily SC injection at bedtime added to participant's pre-study prescribed dose of metformin and /or a sulfonylurea for up to 52 weeks.

Drug: Insulin glargine; Drug: Metformin; Drug: Sulfonylureas

Interventions

Dulaglutide DRUG

Administered SC

Also known as: LY2189265

0.75 mg Dulaglutide; 1.5 mg Dulaglutide

Insulin glargine DRUG

Administered SC per dosing titration schedule

Insulin Glargine

Metformin DRUG

Administered orally at pre-study prescribed dose, and is not being provided as part of the trial.

0.75 mg Dulaglutide; 1.5 mg Dulaglutide; Insulin Glargine

Sulfonylureas DRUG

Administered orally at pre-study prescribed dose, and is not being provided as part of the trial.

0.75 mg Dulaglutide; 1.5 mg Dulaglutide; Insulin Glargine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (30)

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.

Beijing, 100730, China

Location

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.

Changsha, 410011, China

Location

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Chengdu, 610041, China

Location

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Chongqing, 400030, China

Location

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Dalian, 116011, China

Location

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Guangzhou, 510120, China

Location

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Guiyang, 550004, China

Location

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Hangzhou, 310009, China

Location

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Harbin, 150001, China

Location

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Hefei, 230022, China

Location

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Nanchang, 330006, China

Location

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Nanjing, 210006, China

Location

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Nanning, 530021, China

Location

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Shanghai, 200080, China

Location

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Shenyang, 110004, China

Location

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Shijiazhuang, 050051, China

Location

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Wuhan, 430022, China

Location

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Xi'an, 710032, China

Location

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Yangzhou, 225001, China

Location

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Zhenjiang, 212000, China

Location

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Chihuahua City, 31238, Mexico

Location

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.

Monterrey, 64460, Mexico

Location

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Chelyabinsk, 454047, Russia

Location

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Moscow, 127018, Russia

Location

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Saint Petersburg, 190000, Russia

Location

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.

Saint Petersburg, 192012, Russia

Location

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Bucheon-si, 420-717, South Korea

Location

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Kyunggi-Do, 425-020, South Korea

Location

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.

Seoul, 137-701, South Korea

Location

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Wŏnju, 220-701, South Korea

Location

Related Publications (8)

• 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.

  PMID: 34580638 DERIVED

• 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.

  PMID: 34453682 DERIVED

• 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.

  PMID: 33161492 DERIVED

• 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.

  PMID: 32857293 DERIVED

• 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.

  PMID: 32621083 DERIVED

• 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.

  PMID: 32277401 DERIVED

• 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.

  PMID: 31950036 DERIVED

• 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.

  PMID: 31228090 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dulaglutide; Insulin Glargine; Metformin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: July 24, 2012
• Study Start: July 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 18, 2019
• Results First Posted: July 24, 2015

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

ME (2); RU (4); KR (4); CN (20)