Another glucagonlike peptide-1 (GLP1) agonist, dulaglutide (Trulicity, Lilly), is poised to be a new option for glycemic control in youth aged 10-18 years with type 2 diabetes, given as a weekly injection, based on the AWARD-PEDS clinical trial.
The U.S. Food and Drug Administration has already approved daily injection liraglutide (Victoza, Novo Nordisk) in 2019 and weekly exenatide (Bydureon/Bydureon BCise, AstraZeneca) in 2021 for glycemic control in young patients with type 2 diabetes, both of which are also GLP-1 agonists.
AWARD-PEDS showed that youth with type 2 diabetes and obesity treated with or without metformin or basal insulin who received weekly injections of 0.75 mg or 1.5 mg of dulaglutide had lower hemoglobin A1c at 26 weeks than patients who received placebo.
Eli Lilly is now submitting these trial results to the FDA for this indication.
Dulaglutide was cleared for use in adults with type 2 diabetes in the United States in 2014 and was additionally approved for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes at high risk of such events in 2020.
The most common adverse symptoms were gastrointestinal, and the safety profile was consistent with that in adults. However, the drug had no effect on body mass index.
The study was simultaneously published in the New England Journal of Medicine and presented as a late-breaking poster at the annual scientific sessions of the American Diabetes Association in New Orleans.
Might dulaglutide target pathophysiologic impairments in youth?
Dulaglutide would “offer a new treatment that targets the pathophysiologic impairments of type 2 diabetes in youth,” Silva A. Arslanian, MD, lead investigator, told this news organization.
Exenatide is also given as a weekly injection but is associated with a smaller decrease in A1c and does not improve fasting glucose concentrations, plus it requires more steps compared with the dulaglutide single-use pen, said Dr. Arslanian, who is scientific director at the Center for Pediatric Research in Obesity & Metabolism, UPMC Children’s Hospital of Pittsburgh.
“Liraglutide is a daily injection, and I believe most patients, particularly adolescents, would prefer a weekly injection,” she added.
Dr. Elvira Isganaitis
Invited to comment, Elvira Isganaitis, MD, MPH, said “the significance of this paper lies in the fact that options for treating type 2 diabetes in children are currently much more limited than in adults – which is a major problem given recent studies that show that type 2 diabetes in youth is much more aggressive and more likely to cause complications early in the disease course.”
Dr. Isganaitis was not involved with the trial but is an investigator for the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.
“With supply chain shortages and health insurance coverage issues that are common in the U.S., it would be helpful to have more than one FDA-approved option for a weekly GLP-1 receptor agonist in children [and] access to other classes of medications,” added Dr. Isganaitis, a pediatric endocrinologist at the Joslin Diabetes Center, Boston.
Phase 3 trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in youth with type 2 diabetes are also ongoing, Dr. Arslanian noted, “but as always, recruitment is slow with adolescents.”
“I am not optimistic that DPP4 inhibitors will have a place in the treatment of youth with type 2 diabetes,” she said. A recent study showed the addition of sitagliptin to metformin in youth with type 2 diabetes did not provide durable improvement in glycemic control.