Dulaglutide improves HbA1c for youths with type 2 diabetes without rise in BMI
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NEW ORLEANS — Young people with type 2 diabetes taking the once-weekly GLP-1 receptor agonist dulaglutide had a decrease in HbA1c at 26 weeks without a significant change in BMI, according to findings from a phase 3 trial.
“This is a breakthrough in the management of youth type 2 diabetes,” Silva Arslanian, MD, the Richard L. Day professor of pediatrics in the department of pediatric endocrinology, metabolism and diabetes at the University of Pittsburgh School of Medicine, director of the Pediatric Clinical and Translational Research Center, and scientific director for the Center for Pediatric Research in Obesity and Metabolism at Children’s Hospital of Pittsburgh, told Healio. “Dulaglutide is a weekly injection, which simplifies the regimen compared with daily injections, and the pen is easy to use. Further, the improvement in HbA1c and fasting glucose at 26 weeks were significant in each dulaglutide group compared with placebo.”
Arslanian and colleagues conducted a double-blind, placebo-controlled trial of youths aged 10 to 17 years with type 2 diabetes and a BMI in the 85th percentile or higher who were being treated with lifestyle modifications alone or with metformin, with or without basal insulin (mean age, 14.5 years; median BMI, 34.1 kg/m2). Participants were randomly assigned to 0.75 mg dulaglutide (Trulicity, Eli Lilly) once weekly, 1.5 mg dulaglutide once weekly or placebo for 26 weeks. Researchers analyzed the change in HbA1c from baseline to 26 weeks as well as changes in fasting glucose and BMI.
The findings were presented at the American Diabetes Association Scientific Sessions and simultaneously published in The New England Journal of Medicine.
There were 154 participants in the study, with 51 each randomly assigned to the placebo and 0.75 mg dulaglutide groups, and 52 randomly assigned to the 1.5 mg dulaglutide group. At 26 weeks, HbA1c decreased 0.6 percentage points in the 0.75 mg dulaglutide group and 0.9 percentage points in the 1.5 mg dulaglutide group, whereas there was a 0.6 percentage point increase in the placebo group. Of the pooled dulaglutide participants, 51% achieved an HbA1c of less than 7% at 26 weeks compared with 14% of the placebo participants (P < .001). Fasting glucose decreased by 18.9 mg/dL in the pooled dulaglutide participants compared with a 17.1 mg/dL increase in the placebo group (P < .001). There was no significant difference in BMI between participants receiving dulaglutide vs. placebo.
“The findings were somewhat expected based on the adult trials, but the surprising aspect was the degree of improvement, which was greater than other GLP-1 receptor agonist trials in youth,” Arslanian said.
In safety data, a higher percentage of dulaglutide participants reported nausea (14.6% vs. 7.8%), vomiting (15.5% vs. 3.9%) and diarrhea (18.4% vs. 13.7%) compared with placebo. The rates of gastrointestinal adverse events in youths receiving dulaglutide were similar to what was observed in previous trials with adults.
“Pharmacotherapeutic options are very limited in youth with type 2 diabetes,” Arslanian said. “Metformin is the recommended first-line therapy, but failure rates are very high. Dulaglutide offers a therapy that targets the pathophysiological impairments in youth with type 2 diabetes and improves glycemic control.”
Arslanian said more research is needed to uncover why no change in BMI was observed in youth compared with adult trials with dulaglutide.
Reference:
- Arslanian SA, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2204601.
Perspective
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Youth-onset type 2 diabetes is a critical problem, with faster progression and poorer response to several pediatric FDA-approved medications, such as insulin and metformin, than in adults and aggressive development of complications. Newer GLP-1 receptor agonist studies in youth-onset type 2 diabetes include daily liraglutide and once-weekly exenatide.
AWARD-PEDS presents a double-blind, placebo-controlled, 46-center, multi-country, 26-week trial in 154 children with youth-onset of type 2 diabetes using once-weekly dulaglutide (0.75 mg or 1.5 mg) added to lifestyle, metformin and/or basal insulin. While BMI was unchanged, exciting results indicated that both dulaglutide doses improve HbA1c, fasting glucose and percentage of participants achieving HbA1c of less than 7% vs. placebo, and overall dulaglutide had a 0.8% HbA1c reduction at week 26 vs. a 0.6% increase with placebo. Moreover, retention (95%), adherence (98.7%) and medication tolerance (92% of those assigned 1.5 mg tolerated the full dose) at 26 weeks was high. Gastrointestinal side effects were higher with dulaglutide (primarily mild), but injection-site reactions, hypoglycemia (even if on insulin), amylase, lipase and calcitonin were similar to placebo, with no severe hypoglycemia.
Dulaglutide thus appears promising in youth-onset type 2 diabetes, as it was well tolerated and potentially superior to exenatide regarding glycemic impacts in youth-onset type 2 diabetes, which did not lower fasting glucose and produced a smaller HbA1c treatment difference vs. placebo (−0.85%). Moreover, dulaglutide’s and exenatide’s once weekly formulations offer advantages for youths over liraglutide’s need for daily injections. More data are now required on GLP-1 receptor agonist impacts on beta cell function, BMI and diabetes-related complications in youth-onset type 2 diabetes, as well as on the class of SGLT2 inhibitor medications.
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Arslanian SA, et al. 5-LB. Presented at: American Diabetes Association Scientific Sessions; June 3-7, 2022; New Orleans (hybrid meeting).
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