New research shows that that the diabetes/obesity medication tirzepatide can cause clinically meaningful improvements in blood sugar control and weight loss in children and adolescents with type 2 diabetes aged 10-17 years whose diabetes and weight are inadequately controlled with an existing treatment regimen of metformin, insulin, or both.
The study (the SURPASS-PEDS trial), by Dr Tamara Hannon, Division of Pediatric Endocrinology and Diabetology, Indiana University School of Medicine, Indiana University School of Medicine, Indianapolis, USA, and colleagues is presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15-19 September) and published in The Lancet. The study is sponsored by Eli Lilly and company, the manufacturer of tirzepatide.
Youth-onset type 2 diabetes (YT2D) is a rapidly progressing disease with rising incidence in recent years, primarily driven by the increase in the global prevalence of obesity. The overall incidence of type 2 diabetes in children and adolescents in USA has nearly doubled across 15 years, going from 9.0 to 17.9 cases per 100,000 persons per year between 2002-03 and 2017-18.
There are limited treatment options to improve blood sugar (glycaemic) control in YT2D. Existing therapeutics have generally demonstrated lower glycaemic efficacy in YT2D compared to adults with T2D, without clinically meaningful impact on weight as measured by body mass index (BMI). Tirzepatide is a once weekly GIP/GLP-1 receptor agonist approved for the treatment of adults with T2D, obesity, and obstructive sleep apnoea (in the USA, and approved for treating T2D and obesity in many other countries). The safety and efficacy of tirzepatide in YT2D is yet to be reported.
In this phase 3 trial, 99 young people aged 10-17 years with YT2D with inadequate glycaemic control with metformin, basal insulin, or both, were randomized in a 1:1:1 ratio to receive blinded treatment with tirzepatide (5 mg or 10 mg) or placebo (PBO) once weekly for 30 weeks followed by a 22-week open-label extension*. The primary aim was to demonstrate superiority of tirzepatide (looking at the pooled results of both doses combined) versus placebo for change in glycated haemoglobin (HbA1c – a measure of blood sugar control) at 30 weeks. Analyses included all participants who received at least 1 dose of study drug, excluding data after discontinuation of study drug or initiation of glycaemic rescue therapy (this is when a person's blood sugar is so high they need intensive medical treatment to recover).
At baseline, the mean age was 14.7 years, mean duration of diabetes was 2.4 years, and participants were treated with metformin (68.7%), basal insulin (8.1%), or both (23.2%). At 30 weeks, tirzepatide was superior to placebo for improving HbA1c, fasting serum glucose, BMI, and incidence of HbA1c of 6.5% or less (below the range for diabetes) and 5.7% of less (below the range for prediabetes). In the placebo group, these indicators barely changed or did not change across the 30 weeks of the study.
At the start of the study all of the children had HbA1c above 6.5%, classifying them as having type 2 diabetes. At 30 weeks, the pooled tirzepatide results shows that more than three quarters (79%) of children taking tirzepatide had HbA1c of less than 6.5%, and more than half (53%) had and HbA1c of less than 5.7%, compared to 29% and 14% respectively for those taking placebo
And while mean BMI fell just 0.4 points across the 30 weeks in the placebo group, from 34.7 to 34.3 kg/m2, in the pooled tirzepatide group mean BMI fell 9.3 units from 35.6 to 26.3 kg/m2. Fasting glucose levels fell by around 6 times more in the pooled tirzepatide group (2.46 units) than the placebo group (0.44 units)
The estimated mean treatment difference (between tirzepatide pooled results and placebo) for change from baseline were: HbA1c -24.9 mmol/mol (-2.3%), FSG -2.0 mmol/L (-36.3 mg/dL) and BMI -8.9%. At 52 weeks, estimated mean change from baseline in HbA1c was -24.2 mmol/mol (-2.21%) and percent change in BMI from baseline was -12.0%, for TZP pooled.
The most common adverse events on tirzepatide were gastrointestinal, mild to moderate in severity, occurred mostly during dose escalation, and generally decreased over time (consistent with trials in adults). Treatment discontinuation due to adverse events occurred in 6.3% of participants in tirzepatide 5 mg and 0% in tirzepatide 10 mg and placebo. No severe hypoglycaemia episodes were reported during the study. Glycaemic rescue therapy was initiated by 18% of participants in the placebo group and 0 participants in the tirzepatide pooled group.
The authors conclude "Tirzepatide demonstrated significant and clinically meaningful improvements in blood sugar control and BMI in youth with type 2 diabetes. The impact on blood sugar control was sustained over the one year trial period and improvements in BMI continued through the year and did not plateau."
"Tirzepatide is the first drug used for type 2 diabetes in this age group that has shown sustained clinically, meaningful BMI lowering effects…These results support tirzepatide as a potential safe and efficacious treatment option for youth-onset type 2 diabetes."
