Once-weekly Exenatide in youth with Type-2 diabetes

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Type 2 diabetes mellitus (T2DM) among younger individuals, which is typically more aggressive than in adults, is treated with metformin, liraglutide, and/or insulin. However, the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study showed that around 50% of youth with T2DM fail metformin monotherapy within 11.5 months of initiation, while liraglutide is a once-daily injection, making it challenging to maintain adherence. Exenatide is a glucagon-like peptide 1 receptor agonist and can be administered to adults with T2DM on a once-weekly basis. In this international, multicenter (27 sites in six countries), randomized, Phase III study, Dr. Dalia Al-Abdulrazzaq and her collaborators evaluated the efficacy and safety of exenatide injections administered once weekly in children and adolescents, aged 10 to 18 years, with T2DM. This study led to the recent approval of exenatide by the US FDA for treating pediatric patients (10 to 18 years old) with T2DM as an adjunct to diet and exercise.

Eligible patients were either treated with diet or exercise alone, or in combination with an oral glucose-lowering drug, such as metformin or sulfonylurea, and/or insulin. Primary and secondary efficacy endpoints included changes in values from week 24 to baseline of glycated hemoglobin levels, fasting plasma glucose and insulin levels, body weight, and systolic blood pressure, while the safety endpoints included adverse and hypoglycemic events.

The research group found that when exenatide was administered once weekly as an add-on therapy, it outperformed placebo in patients with ineffective treatment for their T2DM, with/without metformin and with/without insulin. Furthermore, once-weekly exenatide injections outperformed placebo in terms of mean change in glycated hemoglobin from baseline (p = 0.012).

Although not statistically significant, participants receiving exenatide had improved glucose control, increased insulin secretion, and lost weight.

Finally, when the placebo group was transferred to the 28-week extension period, during which they were given once-weekly doses of exenatide, they had lower glycated hemoglobin levels. Exenatide’s safety profile was similar to that seen in adults, with no major adverse or hypoglycemic events.

The modest changes in glycated hemoglobin levels observed from baseline were most likely due to the relentlessly progressive nature of T2DM in younger patients, highlighting the need for effective and tolerable therapies aimed at maintaining glycated hemoglobin levels in this population. Current medications for children and adolescents with T2DM do not provide optimal control of glycated hemoglobin; to tackle this, once-weekly exenatide injections may be an effective and safe option.

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