Higher-dose dulaglutide reduces HbA1c, body weight in type 2 diabetes
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Adults with poorly controlled type 2 diabetes assigned higher, investigational doses of the GLP-1 receptor agonist dulaglutide experienced greater improvements in glycemic response and body weight compared with those assigned the currently approved dose of 1.5 mg weekly, with no new safety signals observed, according to findings from the AWARD-11 trial published in the Journal of the Endocrine Society.
“For patients treated with dulaglutide and not achieving desired treatment targets, escalating the dose beyond 1.5 mg weekly may help them achieve their goals without initiating additional antihyperglycemic agents,” Juan Pablo Frias, MD, FACE, medical director and principal investigator of the National Research Institute in Los Angeles, told Healio. “It is important to note that the investigational 3 mg and 4.5 mg doses are not currently approved for use by regulatory agencies.”
Frias and colleagues analyzed data from 1,842 adults with type 2 diabetes inadequately controlled with metformin therapy (mean age, 57 years; mean diabetes duration, 7.6 years; mean HbA1c, 8.6%; mean BMI, 34.2 kg/m²), randomly assigned once-weekly dulaglutide 1.5 mg (Trulicity, Eli Lilly; n = 612), dulaglutide 3 mg (n = 616) and dulaglutide 4.5 mg (n = 614) for 36 weeks. All participants initiated once-weekly dulaglutide 0.75 mg for 4 weeks, followed by a stepwise dose escalation every 4 weeks to the randomized dose of 1.5 mg, 3 mg or 4.5 mg.
Researchers defined two estimands for efficacy analyses: an efficacy estimand, defined as data on-treatment without rescue medication, and a treatment-regimen estimand, defined as all data regardless of adherence or initiation of rescue.
Using the efficacy estimand, researchers found that the 3 mg and 4.5 mg doses of dulaglutide were superior to the 1.5 mg dose for change in HbA1c from baseline. Mean reductions from baseline were 1.53% for the 1.5 mg dose, 1.71% for the 3 mg dose (P = .003) and 1.87% for the 4.5 mg dose (P < .001).
The percentage of participants achieving an HbA1c of 7% across study groups was 57% for the 1.5 mg group, 65% for the 3 mg group (P = .006) and 71% for the 4.5 mg group (P < .001). Mean body weight reductionsfrom baseline were 3.1 kg for the 1.5 mg group, 4 kg for the 3 mg group (P = .001) and 4.7 kg for the 4.5 mg group (P < .001).
Using the treatment-regimen estimand, each of the doses led to HbA1c and body weight reductions; however, only the 4.5 mg dose showed superiority compared with the 1.5 mg dose, according to researchers.
“Importantly, use of these higher doses did not result in clinically relevant differences in safety or tolerability,” Frias said.
The most commonly reported adverse events across each of the doses were gastrointestinal. Treatment discontinuation due to adverse events through 36 weeks was low and similar across dose groups, according to researchers.
“We are encouraged by these data and the potential to provide people living with type 2 diabetes who may need to advance their treatment with options that build on their established experience with Trulicity,” Dawn Brooks, PhD, global development leader, Trulicity, Lilly, said in a press release.
In the release, Lilly stated that results at 52 weeks were consistent with the 36-week results and further details will be disclosed at a later date. The AWARD-11 results have been submitted to regulatory authorities in the U.S. and Europe for review. – by Regina Schaffer
For more information:
Juan Pablo Frias, MD, FACE, can be reached at National Research Institute, 2010 Wilshire Blvd. #302, Los Angeles, CA 90057; email: juan.frias@nritrials.com.
Disclosures: Eli Lilly sponsored the AWARD-11 trial. Frias reports he has received research support from AstraZeneca, Eli Lilly, Novo Nordisk and Sanofi, consulting and advisory fees from Eli Lilly, Novo Nordisk and Sanofi, and speaking fees from Sanofi. Five of the study authors report they are employees of Eli Lilly.
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