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:
- A quick guide to the SURPASS and SURMOUNT trials (tirzepatide)
- A quick guide to the STEP trials (semaglutide for obesity)
- A quick guide to the PIONEER trials (oral semaglutide)
- A quick guide to the SUSTAIN trials (semaglutide)
- A quick guide to the GetGoal trials (lixisenatide)
- A quick guide to the LEAD trials (liraglutide)
- A quick guide to the DURATION trials (exenatide)
AWARD-1: Published
Trial population: People with type 2 diabetes taking metformin and pioglitazone | Comparator treatments: Extended-release exenatide, placebo |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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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