Once-Weekly Exenatide in Youth With Type 2 Diabetes

Abstract

OBJECTIVE Approved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated. RESEARCH DESIGN AND METHODS Participants (aged 10 to <18 years) were randomized (5:2) to once-weekly exenatide 2 mg or placebo, respectively. The primary efficacy end point was change in glycated hemoglobin from baseline to week 24. Secondary efficacy end points were also evaluated, and the frequency of adverse events (AEs) was assessed. RESULTS A total of 83 participants were randomized (exenatide, 59; placebo, 24) and 72 completed 24-week treatment (exenatide, 49; placebo, 23). At 24 weeks, the least squares mean change in glycated hemoglobin was −0.36% for the exenatide and +0.49% for the placebo groups (between-group difference, −0.85%; 95% CI −1.51, −0.19; P = 0.012). Nonsignificant least squares mean differences from baseline to 24 weeks favoring exenatide were observed: fasting glucose −21.6 mg/dL (−49.0, 5.7; P = 0.119), systolic blood pressure −2.8 mmHg (−8.0, 2.4; P = 0.284), and body weight −1.22 kg (−3.59, 1.15; P = 0.307). AEs occurred in 36 (61.0%) and 17 (73.9%) participants in the exenatide and placebo groups, respectively. CONCLUSIONS In youth with type 2 diabetes suboptimally controlled with current treatments, once-weekly exenatide reduced glycated hemoglobin at 24 weeks and was well tolerated.

Real‐world use of glucagon‐like peptide‐1 receptor agonists in youth with type 2 diabetes is associated with short‐term improvements in HbA1c

“…percentage points with dulaglutide 0.75 mg and À0.9 percentage points with dulaglutide 1.5 mg at 26 weeks). 13,14 The findings in this real-world study suggest that results from these clinical trials may be generalizable into academic paediatric clinical practices. However, the lowering effects of GLP-1RAs on HbA1c in paediatric patients were smaller than those generally observed in studies of use of GLP-1RAs in adults with obesity and T2D, 20,21 consistent with the more aggressive nature of T2D in adolescent populations compared with adults.…”

Anti-obesity pharmacotherapy for treatment of pediatric type 2 diabetes: Review of the literature and lessons learned from adults

“…Liraglutide 1.8 mg/day and exenatide ER are not considered AOMs and may not result in clinically significant BMI reduction. Exenatide ER did not significantly reduce weight compared to placebo in 84 adolescents with T2DM, previously treated with diet and exercise alone or with metformin ± a sulfonylurea and/or insulin after 24 and 52 weeks ( 45 , 46 ). In terms of liraglutide, 134 adolescents with T2DM and overweight/obesity treated with doses up to 1.8 mg/day did not have significant BMI reduction after a 26-week double-blind RCT ( 47 , 48 ).…”

Treatment strategy for children and adolescents with type 2 diabetes-based on ISPAD Clinical Practice Consensus Guidelines 2022

“…A second-choice drug should be selected based on the degree of its glucose-lowering effect, mechanism of action, pharmaceutical pricing, approval for use in youth, dosing regimen, adverse events, and influence on comorbidities and complications. A glucagon-like peptide 1 (GLP-1) receptor agonist may be recommended as a second-choice drug if the use is approved in the home country (30,31). With a higher HbA1c value > 9.0% (75 mmol/mol), basal insulin should be started or restated.…”

“…Liraglutide (Victoza 0.6-1.8 mg per day) was subsequently approved by the Food and Drug Administration (FDA) for use in youth aged 12-17 yr; however, it still does not receive approval for use in some areas, including Asian countries. Recently, the long-acting GLP-1 agonist exenatide (Bydureon BCise 2 mg) was approved as a once-weekly injection for children and adolescents aged 10-17 yr based on data from the BCB114 study, which showed superiority to the placebo-control in lowering the HbA1c level, with a mean change of an HbA1c level of -0.85% from the baseline between the groups (p = 0.012) (43). Another weekly GLP-1 receptor agonist (dulaglutide) trial in children is currently underway (NCT02963766).…”