Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4)

NCTNCT01191268Other id11376Other idH9X-MC-GBDD

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 884 participants (actual)
Sponsor: Eli Lilly and Company · Industry
Design: Randomized · Open label (no masking)
Countries: 16 countries
United States, Argentina, Australia, Belgium, Brazil, Canada, Denmark, Greece, Hungary, Mexico, Poland, Puerto Rico, Russia, Spain, Sweden, Taiwan
Start: Nov 2010
Primary completion: Feb 2012
Completion: Sept 2012
First posted: 30 Aug 2010 (estimated)
Last update posted: 8 Oct 2014 (estimated)
Conditions: Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2010201120122013

Ph 3
A Study in Participants With Type 2 Diabetes Mellitus (AWARD-4)
NCT01191268
Nov 2010 to Sept 2012

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study is to assess the efficacy and safety of LY2189265 in comparison to Insulin Glargine, both in combination with Insulin Lispro (plus or minus Metformin), in participants with Type 2 Diabetes treated with 1 or 2 injections of insulin.

Interventions

Insulin GlargineDrug
LY2189265Drug
Insulin LisproDrug

Arms3

Experimental
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Experimental
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks
Active comparator
Insulin Glargine
Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks

Primary outcomes1

Outcomes the sponsor listed as primary.

Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Time frame · Baseline, 26 weeks
Registry description
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.

Secondary outcomes(20)

Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Time frame · Baseline, 52 weeks
Registry description
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52
Time frame · 26 weeks and 52 weeks
Registry description
The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model.
Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
The percentage of participants achieving HbA1c less than 7.0% without nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking) or severe (episodes requiring the assistance of another person to actively administer resuscitative actions) hypoglycemia was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model.
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
The self-monitored plasma glucose (SMPG) data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. The mean of the 8 time points (Daily Mean) was also calculated. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, metformin, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
Fasting serum glucose was measured by the central laboratory. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline fasting blood glucose as a covariate.
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine)
Time frame · Baseline and 26 weeks and 52 weeks
Registry description
Total daily insulin (TDI) dose was reported at baseline, 26 weeks, and 52 weeks. Daily Insulin Lispro and Insulin Glargine doses were reported at 26 and 52 weeks.
Change From Baseline to 26 and 52 Weeks in Body Weight
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline body weight as a covariate.
Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Time frame · Baseline and 52 weeks and 4 weeks after last dose
Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI)
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline BMI as a covariate.
Change From Baseline to 26 and 52 Weeks in the EQ-5D
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
The EQ-5D questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part consists of a visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, metformin use, and baseline.
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL)
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
The Impact of Weight on Activities of Daily Living questionnaire (renamed the Ability to Perform Physical Activities of Daily Living Questionnaire \[APPADL\]) contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = "not at all difficult" and 1 = "unable to do". The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline score as a covariate.
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP)
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline score as a covariate.
Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS)
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
The Low Blood Sugar Survey (LBSS) contains 33 items comprised of 2 subscales (behavior and worry), each of which is rated on a 5-point numeric rating scale from 0 (never) to 4 (almost always). It captures behavioral changes associated with the concerns and experiences of hypoglycemia and the degree to which participants are worried about certain aspects associated with hypoglycemia during the previous 4 weeks. The behavior (or avoidance) subscale has 15 items, and the worry (or affect) subscale has 18 items. Subscale scores are calculated by summing participant responses to items (behavior range 0-60; worry range 0-72). A total score is calculated as the sum of both subscales (range 0-132). Higher scores indicate greater negative impact on subscales and total score. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment and metformin use as fixed effects and baseline score as a covariate.
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured.
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Time frame · Baseline and 52 weeks and 4 weeks after last dose
Registry description
Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured at baseline and at 4 weeks after last dose (ALD).
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin
Time frame · Baseline, 26 weeks, and 52 weeks
Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Time frame · Baseline and 52 weeks and 4 weeks after last dose
Change From Baseline to 26 and 52 Weeks in Blood Pressure
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline blood pressure as a covariate.
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Time frame · Baseline and 52 weeks and 4 weeks after last dose
Registry description
Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured.
Change From Baseline to 26 and 52 Weeks in Pulse Rate
Time frame · Baseline, 26 weeks, and 52 weeks
Registry description
Seated pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline as a covariate

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, 26 weeks

Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)

Group	Value (percentage of glycosylated hemoglobin)	Spread
1.5 mg LY2189265	-1.64	0.07
0.75 mg LY2189265	-1.59	0.07
Insulin Glargine	-1.41	0.07

Secondary and other outcome results(7)

Secondary outcomeLeast squares mean· Baseline, 52 weeks

Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)

Group	Value (percentage of glycosylated hemoglobin)	Spread
1.5 mg LY2189265	-1.48	0.08
0.75 mg LY2189265	-1.42	0.08
Insulin Glargine	-1.23	0.08

Secondary outcomeNumber· 26 weeks and 52 weeks

Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52

Group	Value (percentage of participants)
1.5 mg LY2189265	67.6
0.75 mg LY2189265	69.0
Insulin Glargine	56.8

Secondary outcomeNumber· Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia

Group	Value (percentage of participants)
1.5 mg LY2189265	53.8
0.75 mg LY2189265	54.5
Insulin Glargine	28.2

Secondary outcomeLeast squares mean· Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles

Group	Value (millimoles per liter (mmol/L)])	Spread
1.5 mg LY2189265	-0.36	0.14
0.75 mg LY2189265	-0.06	0.14
Insulin Glargine	-2.01	0.14

Secondary outcomeLeast squares mean· Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose

Group	Value (millimoles per liter (mmol/L))	Spread
1.5 mg LY2189265	-0.27	0.20
0.75 mg LY2189265	0.22	0.20
Insulin Glargine	-1.58	0.20

Secondary outcomeMean· Baseline and 26 weeks and 52 weeks

Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine)

Group	Value (units)	Spread
1.5 mg LY2189265	55.20	32.17
0.75 mg LY2189265	59.11	38.12
Insulin Glargine	53.93	30.67

Secondary outcomeLeast squares mean· Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Body Weight

Group	Value (kilograms (kg))	Spread
1.5 mg LY2189265	-0.87	0.27
0.75 mg LY2189265	0.18	0.27
Insulin Glargine	2.33	0.27

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
1.5 mg LY2189265LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	–	27 / 295	219 / 295
0.75 mg LY2189265LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	–	46 / 293	232 / 293
Insulin GlargineInsulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks	–	53 / 296	203 / 296

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2018

4 results

Dulaglutide 1.5 mg as an add-on option for patients uncontrolled on insulin: Subgroup analysis by age, duration of diabetes and baseline glycated haemoglobin concentration.

Pantalone et al. 2018Diabetes, obesity & metabolismcited by 16

PMID 29430801PMC5969314DOI 10.1111/dom.13252PUB-29430801

Free to read · publisher termsCC BY-NC-ND4 results

Read at source See results (4)

Indexing hint: Randomized controlled trial · 2016

6 results

Patient-reported outcome results in patients with type 2 diabetes treated with once-weekly dulaglutide: data from the AWARD phase III clinical trial programme.

Yu et al. 2016Diabetes, obesity & metabolismcited by 26

PMID 26691396DOI 10.1111/dom.12624PUB-26691396

Full text at the publisher6 results

Publisher page See results (6)

Indexing hint: Randomized controlled trial · 2015

9 results

Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study.

Blonde et al. 2015Lancet (London, England)cited by 185

PMID 26009229DOI 10.1016/s0140-6736(15)60936-9PUB-26009229

Full text at the publisher9 results

Publisher page See results (9)

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedBoustani MA, Pittman I 4th, Yu M, Thieu VT, Varnado OJ, Juneja R. Similar efficacy and safety of once-weekly dulaglutide in patients with type 2 diabetes aged >/=65 and <65 years. Diabetes Obes Metab. 2016 Aug;18(8):820-8. doi: 10.1111/dom.12687. Epub 2016 Jun 7. PMID 27161178

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * Type 2 diabetes * Currently using insulin for at least 3 months with a conventional insulin regimen with or without oral medications * Glycosylated hemoglobin (HbA1c) greater than or equal to 7% and less than or equal to 11% * Willing to inject subcutaneous medication * Willing to monitor blood glucose levels and adjust insulin dose * Willing to maintain a study diary * Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2) * Stable weight for 3 months prior to screening * Females of child bearing potential must test negative for pregnancy at screening and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug Exclusion Criteria: * Type 1 Diabetes * Previous therapy with glucagon-like peptide 1 (GLP-1) agonists within 3 months prior to screening * 1 or more episodes of ketoacidosis within 6 months prior to screening * Have been treated with prescription or over the counter medication to promote weight loss within 3 months prior to screening * Estimated glomerular filtration rate (eGFR) less than or equal to 30 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) at screening * Taking steroids for greater than 14 days except for topical, eye, nasal, or inhaled * History of heart failure, New York Heart Classification III or IV within 2 months prior to screening * Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking medications that directly affect GI motility * Acute or chronic hepatitis or pancreatitis * Self or family history of 2A or type 2B multiple endocrine neoplasia or medullary C-Cell hyperplasia * Serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/mL) at screening * Organ transplant except cornea * Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis * History of or active malignancy except skin or in situ cervical or prostate cancer within the last 5 years * Known drug or alcohol abuse * Have enrolled in another clinical trial within the last 30 days * Have previously signed an informed consent or participated in a LY2189265 study

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