A Review of Interventional Trials in Youth-Onset Type 2 Diabetes: Challenges and Opportunities

Abstract

Introduction: In recent decades, the dramatic rise of obesity among youth in the US has been accompanied by a rise in the prevalence of type 2 diabetes (T2D) in this population. This alarming trend underscores the importance of conducting trials to evaluate new therapies in children with T2D. Methods: A targeted review of peer-reviewed literature and trials registered on www. clinicaltrials.gov was conducted in January 2021 to identify pharmaceutical interventional studies in youth with T2D. Information regarding enrollment data, study design elements, subjects' baseline characteristics, and key treatment outcomes was documented. Results: Among the 16 clinical studies included in this review, only five appeared to meet projected enrollment targets in \ 4 years. Although three other studies met recruitment targets, two took approximately 5 years to complete and the third took nearly 10 years. Conclusions: Despite legislation requiring evaluation of pharmaceutical treatments in pediatric populations, surprisingly few interventional studies have been conducted in children with T2D. This review highlights that recruitment challenges may be impeding the conduct and completion of interventional studies. Consequently, few pharmaceutical treatments have been proven to be effective and approved for children with T2D. Metformin and liraglutide remain the only non-insulin treatments formally approved in the US for use in this population. More clinical research is needed to support regulatory decision-making as well as treatment decisions for children with T2D in clinical settings. Sponsors and investigators will need to implement strategies for improving trial enrollment as well as work with regulatory agencies to develop novel study designs that may require fewer patients.

Unmet Needs in the Treatment of Childhood Type 2 Diabetes: A Narrative Review

“…We then reviewed the titles and abstracts of the search results to identify any clinical trials that focused on treating T2D in youth. Additionally, we selected relevant trials from the ClinicalTrials.gov database ( https://www.clinicaltrials.gov/ ) and assessed eligible recommendations and treatment guidelines from any relevant associations [for e.g., American Diabetes Association (ADA) [ 22 ], European Association for the Study of Diabetes (EASD) [ 23 ], and International Society for Pediatric and Adolescent Diabetes (ISPAD)] [ 24 ]. We also consulted the reference lists of the selected articles to include all relevant studies.…”

“…Despite the significant increase in the prevalence of youth-onset T2D, the number of therapeutic options is limited, in part by the challenges associated with undertaking clinical studies in this patient population [ 22 ]. These challenges include low numbers of participants, restrictive study eligibility criteria, and a small number of research sites worldwide with dedicated resources for youth T2D trials [ 23 , 24 ].…”

Physiologically based pharmacokinetic modelling of semaglutide in children and adolescents with healthy and obese body weights

“…Nevertheless, liraglutide is the glucagon‐like peptide‐1 (GLP‐1) receptor agonist approved for paediatric therapy, 12 although a long‐acting agent would be a better option for treatment adhesion. The recruitment of young people with DM2 for clinical trials is relatively recent and has presented limited success 13,14 . Indeed, a major challenge for academics and the pharmaceutical industry is to achieve a safe and effective dose in paediatric patients 15 …”

“…The recruitment of young people with DM2 for clinical trials is relatively recent and has presented limited success. 13,14 Indeed, a major challenge for academics and the pharmaceutical industry is to achieve a safe and effective dose in paediatric patients. 15 Physiologically based pharmacokinetic (PBPK) models are a valuable approach for integrating known physiological changes that alter drug disposition in children with drug-specific parameters in an untested scenario.…”