medwireNews: Dulaglutide delivers significant reductions in glucose levels for youths with type 2 diabetes, report the AWARD-PEDS investigators.
However, the glucagon-like peptide (GLP)-1 receptor agonist had no significant effect on bodyweight during 26 weeks of treatment, say Silva Arslanian (UPMC Children’s Hospital of Pittsburgh, Pennsylvania, USA) and colleagues.
The findings are published in The New England Journal of Medicine and were also presented in a late-breaking poster at the 82nd ADA Scientific Sessions in New Orleans, Louisiana.
The 154 trial participants were aged at least 10 years but were younger than 18 years (average 14.5 years). They had an average baseline glycated hemoglobin (HbA1c) level of 8.1% (65 mmol/mol) despite treatment with metformin (63%), basal insulin (3%), or both (25%).
HbA1c continued to rise in the youths randomly assigned to receive weekly placebo injections, by an average of 0.6 percentage points (6.2 mmol/mol).
By contrast, it fell in those assigned to receive dulaglutide, by 0.6 percentage points (6.8 mmol/mol) and 0.9 percentage points (10.3 mmol/mol) for those given doses of 0.75 and 1.5 mg/week, respectively, making both doses significantly better than placebo.
Fasting blood glucose also significantly decreased in participants taking dulaglutide, by 35.9 mg/dL (2.0 mmol/L) for the pooled dulaglutide doses versus placebo. Around half (51%) of participants taking dulaglutide achieved HbA1c below 7.0% (53 mmol/mol) compared with just 14% of the placebo group.
However, BMI changed only minimally in any of the treatment groups, with no significant differences between them.
“Although the findings are consistent with two previous trials of GLP-1 receptor agonists in youths with type 2 diabetes, the reasons behind these discrepant findings, as compared with those in adults, remain unclear,” say Arslanian and team.
However, they note evidence from adult studies that the presence of hyperglycemia may impact the weight-reducing efficacy of GLP-1 receptor agonists, and they point out that type 2 diabetes has a more severe course in youths than adults.
The researchers suggest these factors “could potentially render youths more resistant to the weight-reducing effects of GLP-1 receptor agonists.”
They add: “Whether higher doses of GLP-1 receptor agonists or other incretin mimetic agents with more robust effects on weight loss will be more effective for weight management in youths with type 2 diabetes is unknown.”
After week 26, the AWARD-PEDS participants entered an open-label extension period in which those who had been taking placebo switched to dulaglutide 0.75 mg, resulting in an average 0.9 percentage point reduction in HbA1c by week 52.
Those taking dulaglutide continued on the same dose and their HbA1c levels remained significantly below baseline levels despite a tendency to increase again.
The researchers say this “is likely to be related to the rapid underlying disease progression in these youths, as evidenced by the progressive increase in the glycated hemoglobin level in the placebo group through the first 26 weeks.”
Nevertheless, they observe that dulaglutide’s safety profile in the youths was in line with that in adults and conclude that the medication is “potentially promising” for this younger age group.
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N Engl J Med 2022; doi:10.1056/NEJMoa2204601
ADA Scientific Sessions; New Orleans, Louisiana: 3–7 June 2022