Potentially promising therapy
In their published article, Dr. Arslanian and colleagues write that “considering the progressive increase in [A1c] over time that was observed in the TODAY trial, with 34% of youths having [an A1c] of at least 10% after up to 15 years of follow-up, we believe that the effects of dulaglutide therapy appear to be potentially promising.”
The TODAY trial showed that more than 50% of youth with type 2 diabetes taking metformin failed to maintain glycemic control within a median of 11.5 months, Dr. Arslanian elaborated, and over time their A1c escalated while their beta-cell function deteriorated rapidly, and complications progressed quickly.
“Therefore,” she noted, “considering that dulaglutide and the GLP-1 receptor agonist class of drugs improve A1c, improve beta-cell function, suppress glucagon concentrations, and improve insulin sensitivity, dulaglutide would provide a promising new treatment option for youth with type 2 diabetes.”
Phase 3 superiority trial
The AWARD-PEDS trial included 154 youth with type 2 diabetes and a BMI greater than the 85th percentile for their age and sex at 46 centers in nine countries. Researchers randomized participants 1:1:1 to the two doses of dulaglutide or placebo for 26 weeks, followed by a 26-week open-label study (during which the placebo group received 0.75 mg dulaglutide) and a 4-week safety extension.
Participants were a mean age of 14.5 years and had a mean BMI of 34 kg/m2.
In each of the dulaglutide groups, roughly 66% of patients were female and 58% were White, 18% were Black, and about 57% were Hispanic. They had a mean weight of 91 kg (200 lb) and a mean A1c of about 8%; 62% were taking metformin only, 27% were taking metformin plus basal insulin, 3% were taking basal insulin only, and 10% were on diet and exercise only.
At 26 weeks, mean A1c increased by 0.6% in the placebo group but decreased by 0.6% in the 0.75-mg dulaglutide group and by 0.9% in the 1.5-mg dulaglutide group (P < .001 for both comparisons versus placebo).
Also at 26 weeks, more participants in the pooled dulaglutide groups than in the placebo group had an A1c <7.0% (51% vs. 14%; P < .001).
Fasting glucose concentration increased in the placebo group (+17.1 mg/dL ) and decreased in the pooled dulaglutide groups (–18.9 mg/dL; P < .001).
There were no group differences in BMI or adiposity-related parameters even at 52 weeks.
“I believe adolescents may be somewhat resistant to the weight-reducing effects of GLP-1 agonists in diabetes trials (liraglutide and exenatide youth type 2 diabetes trials showed the same thing) and they may need higher doses,” Dr. Arslanian speculated.
“Only future studies will be able to address this issue,” she concluded.
The study was funded by Eli Lilly. Dr. Arslanian has disclosed being a consultant for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; participating in data safety monitoring for AstraZeneca and Eli Lilly trials; and receiving institutional research funding from Eli Lilly and Novo Nordisk. Dr. Isganaitis has disclosed receiving research funding (paid to her institution) from Dexcom and AstraZeneca.
A version of this article first appeared on Medscape.com.