Phase 3 · Dulaglutide

AWARD-CHN2 trial results

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

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks (percentage of HbA1c), Baseline, 26 Weeks. 1.5 mg Dulaglutide: -1.73; 0.75 mg Dulaglutide: -1.33; Insulin Glargine: -1.16.

Participants: 774
Status: completed
Completed: 2014-12
Sponsor: Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT01648582), updated at source Sep 18, 2019. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What AWARD-CHN2 measured first

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weekspercentage of HbA1c · Baseline, 26 Weeks · least squares mean

1.5 mg Dulaglutiden=253	0.75 mg Dulaglutiden=252	Insulin Glarginen=250
-1.73(0.067)	-1.33(0.067)	-1.16(0.067)

Side effects by arm

Side effects in AWARD-CHN2

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

Event	1.5 mg Dulaglutide	0.75 mg Dulaglutide	Insulin Glargine
Any serious event	9.3%	5.8%	3.6%
Hyperlipidaemia	17.8%	19.5%	18.6%
Diarrhoea	16.7%	10.9%	2.8%
Hypertension	7.8%	10.9%	7.5%
Nausea	10.5%	5.4%	0.8%
Lipase increased	10.5%	7%	0.8%
Nasopharyngitis	7%	6.6%	8.7%
Decreased appetite	7.4%	5.4%	0%
Abdominal distension	7%	5.1%	0%
Vomiting	6.2%	2.3%	0.8%
Urinary tract infection	5%	5.4%	4.3%
Upper respiratory tract infection	2.7%	3.9%	5.1%
Dyslipidaemia	3.5%	2.3%	3.6%
Constipation	3.5%	3.1%	0%
Dyspepsia	1.9%	3.1%	0.8%
Headache	3.1%	3.1%	1.2%
Cough	1.2%	0.4%	2.8%
Non-alcoholic fatty liver	1.2%	2.7%	0.8%
Amylase increased	2.7%	1.9%	0.4%
Hyperuricaemia	2.3%	2.7%	1.6%
Abdominal pain upper	2.3%	0.4%	1.2%
Blood cholesterol increased	2.3%	2.3%	0.4%
Blood triglycerides increased	1.6%	2.3%	1.2%
Pharyngitis	0.8%	0.4%	2%
Arthralgia	0.4%	0.8%	2%
Hypoaesthesia	1.2%	0.4%	2%

Secondary outcomes

What else it measured

Change From Baseline in HbA1c at 52 Weekspercentage of HbA1c · Baseline, 52 Weeks · least squares mean

1.5 mg Dulaglutiden=253	0.75 mg Dulaglutiden=252	Insulin Glarginen=250
-1.47(0.076)	-1.03(0.076)	-0.89(0.075)

Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weekspercentage of participants · Up to 26 and 52 weeks · number

Measure	1.5 mg Dulaglutiden=253	0.75 mg Dulaglutiden=252	Insulin Glarginen=250
HbA1c <7%, Week 26	64.8	52.8	40.0
HbA1c ≤6.5%, Week 26	51.4	38.9	21.6
HbA1c <7%, Week 52	51.8	45.6	32.0
HbA1c ≤6.5%, Week 52	37.2	31.3	17.2

Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeksmillimoles per liter (mmol/L) · Baseline, 26 Weeks, 52 Weeks · least squares mean

Measure	1.5 mg Dulaglutiden=253	0.75 mg Dulaglutiden=252	Insulin Glarginen=250
Change from baseline in FBG, 26 Weeks	-2.35(0.162)	-1.71(0.161)	-2.59(0.161)
Change from baseline in FBG, 52 Weeks	-2.23(0.166)	-1.53(0.165)	-2.35(0.164)

Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeksmmol/L · Baseline, 26 Weeks, 52 Weeks · least squares mean

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
Morning pre-meal, Week 26	-2.18(0.104)	-1.89(0.103)	-2.83(0.103)
Morning 2 hours post-meal, Week 26	-3.81(0.190)	-3.43(0.188)	-3.32(0.188)
Mid-day pre-meal, Week 26	-2.45(0.159)	-2.07(0.157)	-2.10(0.157)
Mid-day 2 hours post-meal, Week 26	-3.16(0.182)	-2.71(0.179)	-2.11(0.179)
Evening pre-meal, Week 26	-2.25(0.150)	-1.74(0.147)	-1.62(0.148)
Evening 2 hours post-meal, Week 26	-3.00(0.180)	-2.58(0.178)	-2.11(0.178)
Bed time, Week 26	-2.95(0.170)	-2.51(0.167)	-2.16(0.167)
Morning pre-meal, Week 52	-2.06(0.108)	-1.76(0.108)	-2.83(0.107)
Morning 2 hours post-meal, Week 52	-3.58(0.201)	-3.25(0.200)	-3.05(0.197)
Mid-day pre-meal, Week 52	-2.37(0.162)	-1.89(0.162)	-1.94(0.160)
Mid-day 2 hours post-meal, Week 52	-2.75(0.187)	-2.61(0.186)	-2.12(0.184)
Evening pre-meal, Week 52	-2.15(0.159)	-1.61(0.158)	-1.51(0.156)

Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weekspercentage of HOMA2-%B · Baseline, 26 weeks, 52 weeks · least squares mean

Measure	1.5 mg Dulaglutiden=253	0.75 mg Dulaglutiden=252
Insulin-Based HOMA2-%B, 26 Weeks	34.41(3.831)	31.17(3.761)
Insulin-Based HOMA2-%B, 52 Weeks	45.12(4.147)	36.64(4.061)

Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weekspercentage of HOMA2-%S · Baseline, 26 Weeks, 52 Weeks · least squares mean

Measure	1.5 mg Dulaglutiden=253	0.75 mg Dulaglutiden=252
Insulin-Based HOMA2-%S, Week 26	-6.86(3.649)	-10.03(3.591)
Insulin-Based HOMA2-%S, Week 52	-10.19(3.677)	-12.32(3.609)

Rate of Hypoglycemic Eventsevents per participant per year · Baseline through 26 weeks and 52 weeks · mean

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
1-year Rate of HE, Week 26	1.27(4.485)	0.98(4.202)	2.13(6.724)
Severe HE Week 26	NA(NA)	NA(NA)	NA(NA)
Nocturnal HE Week 26	0.19(0.904)	0.13(0.762)	0.38(1.444)
1-year Rate of HE, Week 52	0.89(3.777)	0.80(3.914)	1.92(6.983)
Severe HE Week 52	NA(NA)	NA(NA)	NA(NA)
Nocturnal HE Week 52	0.11(0.488)	0.10(0.551)	0.31(1.261)

Number of Self-reported Hypoglycemic Eventspercentage of participants · Baseline through 26 Weeks and 52 Weeks · number

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
Total HE Week 26	19.4	16.7	29.6
Severe HE Week 26	0.0	0.0	0.0
Nocturnal HE Week 26	6.2	3.9	11.1
Documented Symptomatic Week 26	11.2	7.8	17.0
Asymptomatic HE Week 26	10.1	8.2	14.2
Probable HE Week 26	4.3	5.1	7.5
Total HE Week 52	22.5	19.8	34.8
Severe HE Week 52	0.0	0.0	0.0
Nocturnal HE Week 52	7.0	4.3	13.8
Documented Symptomatic HE Week 52	12.4	9.7	20.6
Asymptomatic HE Week 52	12.0	10.1	19.4
Probable HE Week 52	4.7	5.4	8.3

Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP)millimeters of mercury (mmHg)] · Baseline, 26 Weeks, 52 Weeks · least squares mean

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
SBP 26 Weeks	-5.53(12.037)	-2.77(11.920)	-2.22(12.743)
DBP 26 Weeks	-1.58(7.842)	-0.92(7.898)	-1.61(8.417)
SBP 52 Weeks	-2.18(11.134)	-0.61(12.081)	-0.25(11.717)
DBP 52 Weeks	-0.19(7.542)	0.44(7.582)	-1.13(8.810)

Change From Baseline at 26 Weeks and 52 Weeks on Pulse Ratebeats per minute (bpm) · Baseline, 26 Weeks, 52 Weeks · least squares mean

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
Change From Baseline on Pulse rate at Week 26	4.63(8.681)	0.65(8.631)	-0.86(9.546)
Change From Baseline on Pulse rate at Week 52	4.18(8.336)	3.18(8.917)	0.07(8.205)

Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Intervalmillisecond (msec) · Baseline, 26 Weeks, 52 Weeks · mean

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
QTcF Interval 26 Weeks	-1.65(13.157)	0.76(11.643)	2.56(11.911)
PR Interval 26 Weeks	3.09(1.700)	2.88(10.801)	-0.86(10.272)
QTcF Interval 52 Weeks	0.55(11.209)	1.19(12.165)	4.03(11.446)
PR Interval 52 Weeks	3.60(12.425)	3.55(11.526)	0.63(11.861)

Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR)beats per minute (bpm) · Baseline, 26 Weeks, 52 Weeks · mean

Measure	1.5 mg Dulaglutiden=258	0.75 mg Dulaglutiden=257	Insulin Glarginen=253
Week 26	6.13(8.924)	3.77(9.002)	-0.46(9.329)
Week 52	5.04(8.223)	3.40(7.986)	0.43(8.060)

The trial

How AWARD-CHN2 was run

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.

1.5 mg Dulaglutide: 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.
0.75 mg Dulaglutide: 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.
Insulin Glargine: 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.

Who could join the trial

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)

Published papers

Papers from AWARD-CHN2

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

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.