Table 1: Summary of paediatric clinical trial results of glucagon-like peptide-1 receptor agonist use in paediatric type 2 diabetes.
| Study | Design | Sample size | Age in years | Main inclusion criteria | Dose | Duration | Efficacy | Safety |
|---|---|---|---|---|---|---|---|---|
| Liraglutide | ||||||||
| Klein et al. (2014)65 | RCT | 21 | 10-17 | HbA1C 6.5-11.0% With lifestyle modifications alone or with metformin, and BMI >85th percentile | 1.8 mg DE: 0.3 mg, 0.6 mg, 1.2 mg, 1.8 mg |
5 weeks | HbA1c change: ETD -0.9%, favouring intervention (p=0.0007) |
Mild AEs in 71.4% of intervention (57.1% with Gl AEs) versus mild AEs in 42.9% of placebo (28.6% with Gl AEs) Transient Gl symptoms = most common AE, during titration No SAEs |
| Tamborlane et al. (2019)6 | RCT | 135 | 10-16 | HbA1c 7.0-11.0% if lifestyle modifications alone or 6.5-11.0% if metformin ± insulin, and BMI >85th percentile | 1.8 mg DE: 0.6 mg, 1.8 mg |
26 weeks + 26 weeks open label | HbA1c change: ETD of -1.06% favouring intervention (p<0.001) Difference increased to -1.30 after 52 weeks Secondary endpoints: HbA1c <7.0%: 63.7% in intervention versus 36.5% in placebo (p<0.001) Intervention group had decrease in fasting plasma glucose level at both time points, compared with increase in placebo |
AEs in 84.8% of intervention versus 80.9% of placebo Rate of AE per 1 patient-year of exposure was higher with intervention than with placebo Gl AEs = most common in intervention, mostly during initial 8 weeks, mild, resolved Mild hypoglycaemia more frequent in intervention (24.2%) versus placebo (10.3%), no severe hypoglycaemia in intervention Lipase levels higher in intervention (treatment ratio 1.20), amylase levels similar SAEs more frequent in intervention (13.6%) versus placebo (5.9%) |
| Exenatide | ||||||||
| Malloy et al. (2009)66 | RCT, crossover | 13 | 10-16 | HbA1c 6.0-11.0%, lifestyle modifications, metformin, or sulphonylurea therapy, and body weight of >50 kg | Three single doses of 2.5 pg or 5 pg, preprandial | Up to 5 weeks | In both dose groups: Reduction in postprandial blood glucose level compared with placebo (p<0.01) Reduction in postprandial glucagon levels compared with placebo (p<0.01) |
AEs in 15% of intervention (2 subjects), AE in one subject was unrelated to study drug No severe or symptomatic hypoglycaemia |
| Tamborlane et al. (2022)5 | RCT | 83 | 10-17 | HbA1c 6.5-11.0% if not taking insulin or sulphonylurea, HbA1c 6.5-12.0% if taking insulin or sulphonylurea | 2 mg extended-release, weekly | 24 weeks + 28 weeks open label | HbA1c change: ETD of -0.85%, favouring intervention group (p=0.012) |
AEs and SAEs less in intervention group: 61.0% of intervention versus 73.9% of placebo; 3.4% of intervention versus 4.3% of placebo, respectively Most Gl AEs were mild or moderate and resolved No major hypoglycaemic events in either group |
| Dulaglutide | ||||||||
| Arslanian et al. (2022)7 | RCT | 154 | 10-17 | HbA1c 6.5-11.0% if taking metformin ± insulin or HbA1c6.5-9.0 if lifestyle modifications alone, and BMI >85th percentile, and body weight >50 kg | 0.75 mg or 1.5 mg | 26 weeks + 26 weeks open label | HbA1c change: -0.6% in the 0.75 mg group and -0.9% in the 1.5 mg group (p<0.001 for both groups versus placebo) ETD of -1.4 for pooled intervention groups versus placebo Secondary endpoints: 51% in intervention with HbA1c of <7.0% versus 14% in placebo (p<0.001) Fasting glucose decreased in the pooled dulaglutide groups by -18.9 mg/dL (p<0.001) Cardiometabolic findings: LDL,TG decreased in intervention |
AEs in 73-75% intervention versus 69% in placebo; SAEs in 2% intervention versus 6% placebo. Gl AEs = most frequent, more in intervention group, mostly mild, mostly transient within 2 weeks of initiation Hypoglycaemia, injection site reaction, hypersensitivity, pancreatic enzyme level, calcitonin level did not differ between groups |
All of the above medications have received United States Food and Drug Administration approval for type 2 diaPetes in age 10 years and above.
AE = adverse event; BMI = body mass index; DE = dose escalation; ETD = estimated treatment difference; Gl = gastrointestinal; HbA 1 c = haemoglobin A1 c; LDL = low-density lipoprotein; RCT= randomized controlled trial; SAE = serious adverse event; T2D = type 2 diabetes; TG = triglycerides.