Pharmacotherapy in paediatric type 2 diabetes mellitus: a protocol for a systematic review and network meta-analysis of randomised trials

Introduction The rates of type 2 diabetes mellitus (T2DM) in children and adolescents have risen globally over the past few years. While a few diabetes pharmacotherapies have been used in this population, their comparative benefits and harms are unclear. Thus, we will conduct a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) to compare the efficacy and safety of pharmacotherapies for managing paediatric T2DM. Methods and analysis We will include RCTs that enrolled T2DM patients <= 18 years of age and who were randomised to monotherapy or combination pharmacotherapies with or without lifestyle interventions. Comparator groups will include placebo or non-pharmacological treatments including lifestyle interventions. Treatment outcomes will include change from baseline in glycated haemoglobin A1c, body mass index z-score, weight, systolic/diastolic blood pressure, fasting plasma glucose, fasting insulin and lipid profiles, T2DM-related complications, as well as the incidence of treatment-related adverse events. Literature searches will be conducted in Medline, Embase, CINAHL, CENTRAL and Web of Science. We will also search the grey literature and the reference list of included trials and relevant reviews. Two reviewers will assess the eligibility of articles identified through our searches and will extract data from eligible studies independently. We will use a modified Cochrane instrument to evaluate the risk of bias. Disagreements will be resolved through consensus or arbitration by a third reviewer. A frequentist random-effects model will be used for conducting NMA. The quality of evidence will be assessed using the Confidence in Network Meta-Analysis platform. We will assess the effect modification through network meta-regression and subgroup analyses for sex, age at study inclusion, duration of T2DM, follow-up duration and risk of bias ratings. Ethics and dissemination This study will not require ethics approval. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations. PROSPERO registration number CRD42022310100.

Automated summary

This study aims to compare the efficacy and safety of different pharmacotherapies in managing pediatric T2DM. The study will include T2DM patients under the age of 18 and evaluate the changes in diabetes control, weight, blood pressure, lipid profiles, as well as the incidence of related complications and adverse events.