The efficacy of automated insulin delivery systems in children and adolescents with type 1 diabetes Mellitus: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Insulin administration is the treatment of choice for people with type 1 diabetes mellitus (T1D). Technological advances have led to the development of automated insulin delivery (AID) systems, aiming to optimize the quality of life of patients with T1D. We present a systematic review and meta-analysis of the current literature about the efficacy of AID systems in children and adolescents with T1D. METHODS: We conducted a systematic literature search for randomized controlled trials (RCTs) until August 8th, 2022, investigating the efficacy of AID systems in the management of patients < 21 years of age with T1D. A priori subgroup and sensitivity analyses based on different settings (free-living settings, type of AID system, parallel group or crossover design) were also conducted. RESULTS: In total, 26 RCTs reporting a total of 915 children and adolescents with T1D were included in the meta-analysis. AID systems revealed statistically significant differences in the main outcomes, such as the proportion of time in the target glucose range (3.9-10 mmol/L) (p < 0.00001), in hypoglycemia (<3.9 mmol/L) (p = 0.003) and mean proportion of HbA1C (p = 0.0007) compared to control group. CONCLUSIONS: According to the present meta-analysis, AID systems are superior to insulin pump therapy, sensor-augmented pumps and multiple daily insulin injections. Most of the included studies have a high risk of bias because of allocation, blinding of patients and blinding of assessment. Our sensitivity analyses showed that patients < 21 years of age with T1D can use AID systems, after proper education, following their daily activities. Further RCTs examining the effect of AID systems on nocturnal hypoglycemia, under free-living settings and studies examining the effect of dual-hormone AID systems are pending.

Antigen-based immunotherapies do not prevent progression of recent-onset autoimmune diabetes: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis to assess the efficacy and safety of antigen-based immunotherapies in tertiary prevention of autoimmune diabetes. We searched for randomised controlled trials testing antigen-based immunotherapies in patients with recent-onset type 1 diabetes or latent autoimmune diabetes of adults in MEDLINE, COCHRANE and EMBASE databases, trial registries, conference proceedings and reference lists of pertinent records. Primary outcomes were fasting and stimulated C-peptide (after glucagon or mixed meal stimulation). Change in glycosylated haemoglobin (HbA1c), daily insulin needs and incidence of any or severe hypoglycaemic events or severe adverse events were secondary outcomes. Fifteen studies were included in the meta-analysis. Overall, there was no difference in fasting [weighted mean difference (WMD) 0.01 nmol/L; 95 % confidence interval (CI) -0.09, 0.11; I 2 = 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI -0.08, 0.12; I 2 = 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I 2 = 0 %) in patients treated with Diapep277. Moreover, there was no change in daily insulin needs (WMD 0.02 IU/kg; 95 % CI -0.04, 0.09; I 2 = 51 %) or HbA1c (WMD -0.06 %; 95 % CI -0.35, 0.23; I 2 = 42 %) vs. placebo. Finally, there was no effect on the incidence of severe hypoglycaemic events or overall serious adverse events [risk ratio 0.94, 95 % CI 0.62, 1.41; I 2 = 0 % and 0.87; 95 % CI 0.53, 1.44; I 2 = 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.