AWARD 11 supports higher dulaglutide doses
medwireNews: Dulaglutide doses of 3.0 and 4.5 mg are significantly more efficacious than the standard doses, with similar safety profiles, report the AWARD 11 investigators.
David Cox (Eli Lilly and Company, Indianapolis, USA) and colleagues note that the originally tested weekly doses of 0.75 and 1.5 mg were selected with safety concerns in mind, such as heart rate increases and gastrointestinal (GI) adverse events.
But in this trial, involving 1842 people with type 2 diabetes, the higher doses tested had similar safety profiles to that of the 1.5 mg/week dose over 52 weeks of treatment.
The overall adverse event rates were 62.1%, 62.3%, and 66.4% among participants randomly assigned to receive the 1.5, 3.0, and 4.5 mg doses, respectively, the researchers report in Diabetes Care.
GI adverse events were the most frequent, particularly nausea, which occurred in 14.2%, 16.1%, and 17.3% of the 1.5, 3.0, and 4.5 mg dose groups, respectively. Diarrhea occurred in a corresponding 7.7%, 12.0%, and 11.6%, and vomiting in 6.4%, 9.1%, and 10.1%.
These GI effects were most severe early in treatment and diminished over time. The proportion of people who discontinued dulaglutide due to GI side effects was low, at 1.5%, 3.4%, and 3.9% for those taking 1.5, 3.0, and 4.5 mg, respectively.
Adjudication-confirmed acute pancreatitis occurred in just six people, including one in the dulaglutide 4.5 mg group with a previously undisclosed history of pancreatitis. Average heart rate increases at 52 weeks were 1.0 bpm with dulaglutide 1.5 mg and 1.9 bpm with both higher doses.
When considering all treated participants regardless of medication-taking consistency or rescue medication, efficacy at 36 weeks was significantly greater for the 4.5 mg dose than the 1.5 mg dose, with an average glycated hemoglobin (HbA1c) reduction of 1.77% versus 1.54%.
This analysis gives “a conservative estimate of overall effectiveness in populations in which patients may not adhere to treatment or may initiate other therapies,” say Cox and team.
They note that the 3.0 mg dose did not produce a significantly greater HbA1c reduction than the 1.5 mg dose, but did result in a clinically relevant improvement, at 1.64% versus 1.54%, which “should have clinical utility in patients requiring treatment intensification.”
When considering on-treatment efficacy without rescue medication, both higher doses were significantly more efficacious than the 1.5 mg dose, giving HbA1c reductions averaging 1.71% and 1.87% for the 3.0 and 4.5 mg doses, respectively, versus 1.53%.
There was a similar dose-dependent pattern for weight loss, which averaged between 3 and 5 kg depending on the dulaglutide dose and timepoint (36 or 52 weeks).
“The availability of four clinically efficacious dulaglutide doses provides additional tools to individualize patient care, helping patients achieve and maintain glycemic and weight-reduction goals and allowing those already taking 1.5 mg to intensify treatment while continuing to receive a familiar therapy,” the researchers conclude.
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