Phase 3 · Dulaglutide

AWARD-2 trial results

A Randomized, Open-Label, Parallel-Arm, Noninferiority Comparison of the Effects of Two Doses of LY2189265 and Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Glimepiride

Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) (percentage of glycosylated hemoglobin), Baseline, 52 weeks. LY2189265 1.5 mg: -1.08; LY2189265 0.75 mg: -0.76; Insulin Glargine: -0.63.

Participants: 810
Status: completed
Completed: 2012-11
Sponsor: Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT01075282), updated at source Jan 16, 2015. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What AWARD-2 measured first

Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)percentage of glycosylated hemoglobin · Baseline, 52 weeks · least squares mean

LY2189265 1.5 mgn=263	LY2189265 0.75 mgn=267	Insulin Glarginen=259
-1.08(0.06)	-0.76(0.06)	-0.63(0.06)

Side effects by arm

Side effects in AWARD-2

Percent of participants affected. The most common events the registry lists.

Event	LY2189265 1.5 mg	LY2189265 0.75 mg	Insulin Glargine
Any serious event	11.7%	10.3%	12.6%
Nausea	15.4%	8.1%	1.5%
Diarrhoea	10.6%	9.6%	5.7%
Nasopharyngitis	5.9%	4.4%	9.2%
Headache	8.1%	3.3%	5%
Dyspepsia	7%	3.3%	2.3%
Vomiting	6.6%	3.7%	1.1%
Upper respiratory tract infection	5.5%	4%	6.5%
Urinary tract infection	4.4%	6.3%	5.7%
Bronchitis	3.3%	2.6%	5.3%
Influenza	4.4%	4.8%	5.3%
Abdominal pain upper	5.1%	3.3%	0.8%
Pancreatic enzymes increased	4.8%	3.3%	1.5%
Hypertension	4.4%	4.8%	4.2%
Arthralgia	1.1%	2.9%	4.6%
Abdominal pain	4.4%	1.1%	1.9%
Constipation	4.4%	1.1%	1.1%
Decreased appetite	3.7%	4.4%	0.4%
Pain in extremity	4.4%	3.7%	1.1%
Back pain	1.8%	4%	3.1%
Dyslipidaemia	3.3%	2.9%	1.5%
Dizziness	3.3%	0.7%	1.9%
Cough	3.3%	2.9%	2.3%
Viral infection	1.5%	1.5%	3.1%

Secondary outcomes

What else it measured

Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)percent · Baseline, 26 weeks, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=262
26 weeks (n=263, 266, 258)	-1.16(0.06)	-0.89(0.05)	-0.65(0.06)
78 weeks (n=263, 267, 259)	-0.90(0.07)	-0.62(0.07)	-0.59(0.07)

Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeksparticipants · 26, 52, and 78 weeks · number

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=262
26 weeks (n=263, 266, 258)	153	122	84
52 weeks (n=263, 267, 259)	140	99	80
78 weeks (n=263, 267, 259)	129	91	79

Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeksparticipants · 26, 52, and 78 weeks · number

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=262
26 weeks (n=263, 266, 258)	97	74	40
52 weeks (n=263, 267, 259)	71	60	35
78 weeks (n=263, 267, 259)	74	59	43

Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profilesmillimoles per liter (mmol/L) · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=231	LY2189265 0.75 mgn=242	Insulin Glarginen=228
26 weeks (n=199, 204, 190)	-1.79(0.10)	-1.46(0.10)	-1.58(0.10)
52 weeks (n=180, 185, 176)	-1.69(0.11)	-1.32(0.11)	-1.44(0.11)
78 weeks (n=172, 164, 168)	-1.55(0.13)	-1.15(0.12)	-1.47(0.13)

Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)percentage of HOMA2 · Baseline, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=222	LY2189265 0.75 mgn=230
HOMA2-%B, 52 weeks (n=175, 181)	29.95(4.61)	24.60(4.51)
HOMA2-%B, 78 weeks (n=167, 165)	28.54(4.78)	15.66(4.75)
HOMA2-%S, 52 weeks (n=175,181)	-2.89(1.21)	-2.66(1.19)
HOMA2-%S, 78 weeks (n=167, 165)	-2.64(1.23)	-3.62(1.23)

Change From Baseline to 52 and 78 Weeks in Glucagon Concentrationpicomoles per liter (pmol/L) · Baseline, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=235	LY2189265 0.75 mgn=235	Insulin Glarginen=232
52 weeks (n=232, 231, 228)	-3.91(0.47)	-3.31(0.47)	-3.85(0.47)
78 weeks (n=235, 235, 232)	-3.57(0.47)	-3.37(0.47)	-3.65(0.47)

Change From Baseline to 26, 52 and 78 Weeks for Body Weightkilogram (kg) · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=272	LY2189265 0.75 mgn=270	Insulin Glarginen=259
26 weeks	-1.82(0.20)	-1.47(0.20)	1.01(0.20)
52 weeks	-1.87(0.24)	-1.33(0.24)	1.44(0.24)
78 weeks	-1.96(0.26)	-1.54(0.26)	1.28(0.26)

Change From Baseline to 26, 52 and 78 Weeks for Body Mass Indexkilograms per square meter (kg/m^2) · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=262
26 weeks (n=257, 261, 245)	-0.64(0.07)	-0.50(0.07)	0.44(0.07)
52 weeks (n=250, 252, 238)	-0.64(0.08)	-0.39(0.08)	0.62(0.08)
78 weeks (n=246, 244, 238)	-0.64(0.09)	-0.39(0.09)	0.59(0.10)

Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimensionunits on a scale · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=262
EQ-5D UK, 26 weeks (n=257, 254, 249)	0.01(0.01)	0.00(0.01)	-0.01(0.01)
EQ-5D UK, 52 weeks (n=259, 260, 253)	0.01(0.01)	0.00(0.01)	-0.04(0.01)
EQ-5D UK, 78 weeks (n=259, 260, 253)	0.01(0.01)	0.00(0.01)	0.00(0.01)
VAS, 26 weeks (n=253, 252, 243)	3.3(0.83)	3.4(0.84)	0.8(0.86)
VAS, 52 weeks (n=260, 258, 252)	3.2(0.85)	2.3(0.85)	1.1(0.88)
VAS, 78 weeks (n=260, 258, 252)	3.8(0.85)	3.2(0.85)	2.2(0.89)

Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Livingunits on a scale · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=260
26 weeks (n=256, 256, 248)	0.7(0.30)	0.1(0.30)	-0.3(0.30)
52 weeks (n=260, 261, 249)	0.9(0.31)	0.4(0.31)	-0.6(0.32)
78 weeks (n=260, 261, 249)	1.0(0.31)	0.3(0.31)	-0.3(0.32)

Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perceptionunits on a scale · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=273	LY2189265 0.75 mgn=272	Insulin Glarginen=262
26 weeks (n=258, 258, 251)	0.1(0.16)	0.2(0.16)	-0.1(0.16)
52 weeks (n=260, 261, 252)	0.5(0.16)	0.2(0.16)	0.1(0.16)
78 weeks (n=260, 261, 252)	0.5(0.16)	0.3(0.15)	0.1(0.16)

Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Surveyunits on a scale · Baseline, 26, 52, and 78 weeks · least squares mean

Measure	LY2189265 1.5 mgn=270	LY2189265 0.75 mgn=271	Insulin Glarginen=255
26 weeks (n=255, 255, 244)	-2.8(0.95)	-2.4(0.96)	0.3(0.98)
52 weeks (n=258, 259, 245)	-4.2(0.83)	-4.1(0.83)	-1.0(0.86)
78 weeks (n=258, 259, 245)	-4.6(0.82)	-4.7(0.82)	-2.0(0.85)

The trial

How AWARD-2 was run

The purpose of this study is to determine if LY2189265 is effective in reducing hemoglobin A1c (HbA1c) and safe, as compared to Insulin Glargine in participants with Type 2 Diabetes. Participants must also be taking metformin and glimepiride.

LY2189265 1.5 mg: LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
LY2189265 0.75 mg: LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks
Insulin Glargine: Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks Glimepiride: at least 4 mg/day, oral, for 78 weeks

Who could join the trial

Inclusion Criteria: * Type 2 Diabetes not well controlled on 1, 2, or 3 oral antidiabetic medications (at least one of them must be metformin and/or a sulfonylurea) 1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication 2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications * Accept treatment with metformin and glimepiride throughout the study, as per protocol * Willing to inject subcutaneous medication once weekly for LY2189265 or once daily for Insulin Glargine. * Stable weight for 3 months prior to screening * Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2) * Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test 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 * HbA1c equal to or less than 6.5 at randomization * Chronic insulin use * Taking drugs to promote weight loss by prescription or over the counter * Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled * History of Heart Failure New York Heart Classification III or IV, or acute myocardial infarction, or stroke within 2 months of screening * Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility * Hepatitis or liver disease or ALT (alanine transaminase) greater than 3.0 of upper normal limit * Acute or chronic pancreatitis of any form * Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatinine clearance of less than 60 milliliters per minute (ml/min) * History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer * A serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/ml) at screening * Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis * History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years * Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing * Organ transplant except cornea * Have enrolled in another clinical trial within the last 30 days * Have previously signed an informed consent or participated in a LY2189265 study * Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening

Published papers

Papers from AWARD-2

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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