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02-07-2022 | Dulaglutide | At a glance | Article

A quick guide to the AWARD trials

Author: Eleanor McDermid

medwireNews: Dulaglutide is a weekly injectable glucagon-like peptide (GLP)-1 receptor agonist currently approved for the treatment of people with type 2 diabetes at a dose of 1.5 mg/week.

Here we round up the efficacy findings from the AWARD clinical trial series, which includes completed and ongoing trials of dulaglutide in a range of adult populations and a study in children.

As with the other GLP-1 receptor agonists, gastrointestinal issues were the predominant adverse events in all the trials.

The REWIND trial tested the cardioprotective ability of dulaglutide, and is covered in our Round-up of the GLP-1 receptor agonist CV outcome trials.

See also:

AWARD-1: Published

Trial population: People with type 2 diabetes taking metformin and pioglitazone

Comparator treatments: Extended-release exenatide, placebo

NCT01064687

The 976 AWARD-1 participants were stabilized on metformin and pioglitazone and then randomly assigned to receive dulaglutide at 1.5 or 0.75 mg/week, exenatide, or placebo.

After 26 weeks, the average reductions in glycated hemoglobin (HbA1c) for these groups were 1.51%, 1.30%, 0.99%, and 0.46%, respectively. Both dulaglutide doses achieved statistically larger HbA1c reductions than exenatide did.

Participants lost an average of 1.30 kg bodyweight with dulaglutide 1.5 mg, and 1.07 kg with exenatide, but gained an average of 0.20 kg with dulaglutide 0.75 mg and 1.24 kg with placebo.

The trial results were published in Diabetes Care in 2014.

AWARD-2: Published

Trial population: People with type 2 diabetes talking metformin and glimepiride

Comparator treatment: Insulin glargine

NCT01075282  

In AWARD-2, also published in Diabetes Care, 807 people with type 2 diabetes were randomly assigned to receive dulaglutide at 1.5 or 0.75 mg/week or insulin glargine.

The lower dulaglutide dose gave comparable results to glargine, at respective 0.76% and 0.63% reductions in HbA1c after 52 weeks, but the high dose was significantly better, producing a 1.08% reduction.

Both dulaglutide doses resulted in weight loss, averaging 1.87 and 1.33 kg with the 1.5 and 0.75 mg doses, respectively. Both were significantly better for weight loss than glargine, which produced an average gain of 1.44 kg.

AWARD-3: Published

Trial population: People with type 2 diabetes taking no more than one oral medication for no more than 3 months

Comparator treatment: Metformin

NCT01126580

When tested as a monotherapy in 807 participants, both the 1.5 and 0.75 mg/week doses of dulaglutide produced significantly better glucose control than the standard first-line treatment of metformin. The average HbA1c reductions over 26 weeks of treatment were 0.78% and 0.71% with 1.5 and 0.75 mg dulaglutide, respectively, compared with 0.56% with metformin.

As reported in Diabetes Care, the corresponding average weight reductions were 2.29, 1.36, and 2.22 kg, with the highest dulaglutide dose being noninferior to metformin.

AWARD-4: Published

Trial population: People with insulin-treated type 2 diabetes

Comparator treatment: Insulin glargine

NCT01191268

All 884 participants of the AWARD-4 trial used a prandial insulin (lispro) but were randomly assigned to either continue basal insulin (glargine; treat to target) or replace it with dulaglutide.

The results published in The Lancet showed that dulaglutide at both the 1.5 and 0.75 mg doses gave significantly better glycemic control than glargine, with HbA1c reductions at week 26 averaging 1.64%, 1.59%, and 1.41%, respectively. The differences persisted to week 52.

After initial weight loss during the first few months of the trial, the dulaglutide-treated participants regained weight. However, bodyweight at week 52 did not significantly exceed that at baseline in the dulaglutide 1.5 mg group, and the weight gain in the 0.75 mg group was significantly less than that in the glargine group.

AWARD-5: Published

Trial population: People with type 2 diabetes taking metformin

Comparator treatments: Sitagliptin, placebo

NCT00734474

The first part of AWARD-5 was published in Diabetes, Obesity and Metabolism in April 2014. It was an adaptive dose-finding trial, which determined an optimal dulaglutide dose of 1.5 mg versus sitagliptin and placebo, with 0.75 mg as a lower-dose option in case of unforeseen safety issues.

The full 104-week trial, published in the same journal a year later, revealed average HbA1c reductions of 0.99% and 0.71% with dulaglutide 1.5 and  0.75 mg, respectively, which were both significantly greater than the 0.32% reduction achieved with sitagliptin.

Average weight reductions were a corresponding 2.88, 2.39, and 1.75 kg. The weight reduction achieved with dulaglutide 1.5 mg was significantly greater than that achieved with sitagliptin.

AWARD-6: Published

Trial population: People with type 2 diabetes taking metformin

Comparator treatment: Liraglutide

NCT01624259

The AWARD-6 trial, involving 599 participants and published in The Lancet, demonstrated noninferiority of dulaglutide 1.5 mg to daily injections of liraglutide 1.8 mg in people already taking metformin.

Dulaglutide and liraglutide treatment resulted in average HbA1c reductions of 1.42% and 1.36%, respectively, and weight loss averaging 2.90 and 3.61 kg.

AWARD-7: Published

Trial population: People with type 2 diabetes and moderate-to-severe chronic kidney disease taking metformin

Comparator treatment: Insulin glargine

NCT01621178

In this trial, published in The Lancet Diabetes & Endocrinology, participants taking either dose of dulaglutide achieved similar glycemic control to those taking insulin glargine, but had significantly less decline in kidney function.

HbA1c decreased by an average 1.2% with the 1.5 mg dose compared with 1.1% with glargine across 26 weeks, and across 52 weeks estimated glomerular filtration rate declined by a corresponding 0.7 and 3.3 mL/min per 1.73 m2.

Bodyweight again decreased in people taking dulaglutide but rose in those taking glargine.

AWARD-8: Published

Trial population: People with type 2 diabetes on glimepiride monotherapy

Comparator treatment: Placebo

NCT01769378

In AWARD-8, the 239 participants given dulaglutide 1.5 mg had an average 1.4% reduction in HbA1c during 24 weeks of treatment, which was significantly greater than the 0.1% reduction achieved by the 60 given placebo.

The corresponding average weight reductions were 0.91 and 0.24 kg, but the difference between the groups was not statistically significant.

The results are published in Diabetes, Obesity and Metabolism.

AWARD-9: Published

Trial population: People with type 2 diabetes taking basal insulin with/without metformin

Comparator treatment: Placebo

NCT02152371

This trial tested dulaglutide as an add-on to insulin glargine, rather than as a replacement for it as in AWARD-4. The 150 participants assigned to take dulaglutide had an average 1.44% reduction in HbA1c, compared with a 0.67% reduction in the 150 taking placebo. The between-group difference of 0.77% was statistically significant.

As reported in Diabetes, Obesity and Metabolism, dulaglutide treatment reduced bodyweight by an average of 1.91 kg, whereas this increased by 0.50 kg in the placebo group.

AWARD-10: Published

Trial population: People with type 2 diabetes taking an SGLT2 inhibitor with/without metformin

Comparator treatment: Placebo

NCT02597049

As reported in The Lancet Diabetes & Endocrinology, this trial showed that dulaglutide treatment could improve glucose control in people who had poor control despite taking an SGLT (sodium-glucose cotransporter)2 inhibitor.

During 24 weeks’ treatment of 424 trial participants, HbA1c fell by an average of 1.34% and 1.21% in those given dulaglutide 1.5 and 0.75 mg, respectively. Both reductions were significantly greater than the 0.54% decrease achieved in the placebo group.

Bodyweight fell by an average of 3.1, 2.6, and 2.1 kg in the three groups, respectively. Only the difference between the highest dulaglutide dose and placebo was statistically significant.

Related news story: AWARD-10 supports GLP-1 receptor agonist–SGLT2 inhibitor combination 

AWARD-11: Published

Trial population: People with type 2 diabetes taking metformin

Comparator treatment: Dulaglutide 1.5 mg

NCT03495102

With the original 0.75 and 1.5 mg doses having been selected with safety in mind, this trial, published in Diabetes Care, aimed to test the efficacy of 3.0 and 4.5 mg/week doses.

The investigators found these higher doses to have similar safety profiles to the established 1.5 mg dose. Nausea, for example, occurred in 17.3%, 16.1%, and 14.2% of participants (n=1842) taking the 4.5, 3.0, and 1.5 mg doses, respectively.

The average HbA1c reductions were 1.77%, 1.64%, and 1.54%, respectively. The reduction achieved with the 4.5 mg dose was significantly greater than that achieved with 1.5 mg, whereas 3.0 mg resulted in a nonsignificant decrease that the researchers nonetheless described as clinically relevant.

Related news story: AWARD 11 supports higher dulaglutide doses


Studies in East Asian people

AWARD-CHN1: Published

Trial population: East Asian people with type 2 diabetes – medication naïve or taking monotherapy (not incretin-based)

Comparator treatment: Glimepiride

NCT01644500

Across 26 weeks’ treatment of 720 study participants, the average HbA1c reductions were 1.48%, 1.22%, and 0.90% with dulaglutide 1.5 and 0.75 mg, and glimepiride, respectively. Both doses of dulaglutide were significantly superior to glimepiride.

The average weight changes were a 1.46 and 0.77 kg reduction with dulaglutide 1.5 and 0.75 mg, respectively, versus a 0.89 kg increase with glimepiride.

The findings were published in Diabetes, Obesity and Metabolism.

AWARD-CHN2: Published

Trial population: Predominantly East Asian people with type 2 diabetes taking metformin or a sulfonylurea

Comparator treatment: Insulin glargine

NCT01648582

This study, published in Diabetes, Obesity and Metabolism, demonstrated the superiority of dulaglutide to glargine for glucose control and weight reduction in 755 participants, most of whom (>80%) were of East Asian origin.

The average HbA1c reductions at week 26 were 1.73% and 1.33% for dulaglutide 1.5 and 0.75 mg, respectively, compared with 1.16% for glargine. The corresponding bodyweight changes were 1.47 and 0.88 kg reductions versus a 0.97 kg increase.

AWARD-CHN3: Active, not recruiting

Trial population: Predominantly East Asian people with type 2 diabetes taking insulin plus metformin with or without acarbose

Comparator treatment: Placebo

NCT04591626

This trial, expected to complete in April 2022, is testing dulaglutide versus placebo in an estimated 290 Chinese people.


A study in children

AWARD-PEDS: Published

Trial population: Children aged 10–17 years with type 2 diabetes taking metformin and/or insulin

Comparator treatment: Placebo

NCT02963766

This pediatric type 2 diabetes trial, published in The New England Journal of Medicine, recruited 154 participants aged at least 10 years but younger than 18 years.

During 26 weeks of treatment, those given dulaglutide had HbA1c reductions averaging 0.6 percentage points (6.8 mmol/mol) and 0.9 percentage points (10.3 mmol/mol) with the 0.75 and 1.5 mg/week doses, respectively.

By contrast, HbA1c continued to rise in the placebo group, resulting in a significant difference favoring dulaglutide. The were no treatment-related differences in BMI, however.

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