ESPE Yearbook of Paediatric Endocrinology

N Engl J Med. 2021;385(6):503-15. doi: 10.1056/NEJMoa2107519.PubMed ID: 34170647

Brief summary: this randomized control trial in 1879 adults with type 2 diabetes compared effects of once-weekly Tirzepatide (5, 10 or 15 mg) versus once-weekly Semaglutide (1 mg) on glycemic control. After 40 weeks, all doses of Tirzepatide were superior to Semaglutide on lowering HbA1c.

Glucagon-like peptide-1 (GLP-1) receptor agonists, Liraglutide (given once-daily) and Semaglutide (once-weekly), are increasingly used in adult patients with obesity and impaired glucose tolerance or type 2 diabetes, following consistent trial evidence regarding their effectiveness to reduce body weight and lower glucose levels. Liraglutide is licensed for use in children aged 10 years and older with type 2 diabetes and we are eagerly looking forward to its wider licensing and funding approvals, as well as similar approvals for Semaglutide. However there are other gut derived peptides beyond GLP-1, which may have similar potent effects on body weight and glucose metabolism.

Tirzepatide is a ‘dual agonist’, which combines actions on GLP-1 receptors and also on glucose-dependent insulinotropic polypeptide (GIP) receptors. A major pharmacokinetic advantage is its once weekly administration, although like Semaglutide it is given by subcutaneous injection. The current findings are impressive, showing that the dual agonist Tirzepatide at all doses tested is superior to the single agonist Semaglutide in controlling glycemic levels in type 2 diabetes. Tirzepatide was subsequently approved for this indication by the FDA in May 2022.

However as well as its superior effects on HbA1c, in this trial Tirzepatide was also more effective than Semaglutide in reducing body weight, again at all doses. Further data released in April 2022, confirmed the remarkable effectiveness of Tirzepatide on body weight, which was on average 24 kg lower on the 15 mg dose after 72 weeks (1). We look forward to seeing this evidence in publication, as well as further evidence on the effects of both Tirzepatide and Semaglutide on body weight and HbA1c in children.