To the best of our knowledge, this is the first meta-analysis focused on the efficacy and safety of GLP-1 RA in pediatric patients with T2DM. Unlike previous meta-analyses that encompassed pediatric patients with obesity, which potentially compromised sample representativeness, our analysis reveals distinctive effect sizes. Although these studies align with adult findings, our examination exposes variations in effect sizes. It is uncertain whether one medication is superior to the other due to the insufficient number of trials with each GLP-1 RA to perform a subgroup or network meta-analysis. Moreover, some studies have a small population, which interferes drastically with confidence intervals in the original studies and with individual analysis. Our findings demonstrate that, on average, GLP-1 RA reduces HbA1c by 1%, fasting blood glucose by 1.88 mmol/L, and body weight by 1.6 kg. Notably, no significant reduction in SBP or DBP was observed. Despite a higher incidence of side effects, including hypoglycemia, vomiting, and diarrhea, associated with GLP-1 RA therapy, withdrawal rates from the studies remained low. Furthermore, the consistently low I² in most analyses indicates data accuracy.

The impact on HbA1c and body weight mirrors that observed in adults; however, these medications exhibit heightened efficacy in lowering fasting blood glucose in children [15, 16]. As anticipated, there is a lack of significance in DBP changes in children, paralleling the pattern observed in adults [17]. Conversely, SBP reductions are evident in adults but not in children, likely due to the low prevalence of hypertension in the latter [18, 19].

According to the findings from obesity meta-analyses, children with T2DM tend to lose weight to a lesser extent [20, 21]. Chadda et al. demonstrated a weight loss of 0.97 kg in children with T2DM, which was not statistically significant. In contrast, patients with obesity but without diabetes significantly lost 2.74 kg [20]. This parallels what is observed in adults with T2DM, potentially due to concurrent insulin use in some trials. Additionally, we observed a high risk for hypoglycemia, which mimics findings in adults, and we hypothesize that this may also be due to insulin use [22].

Lowering glycated hemoglobin stands as a paramount objective in the management of youth-onset T2DM. These young individuals confront an elevated risk of developing target organ damage, including diabetic retinopathy and kidney disease, along with a heightened mortality rate compared to their counterparts with type 1 diabetes [4, 23, 24]. However, attaining glycemic control poses a formidable challenge in children and adolescents with T2DM [25]. The onset of the disease during youth is correlated with higher rates of metformin monotherapy failure and a less favorable glycemic trajectory compared to adult-onset disease [26].

Presently, American guidelines advocate for the use of GLP-1 receptor agonists as second-line treatments for both children and adults for primary prevention of macrovascular disease [9, 27,28,29]. The paucity of evidence has not only curtailed the indication of GLP-1 RA but has also confined it to specific pharmaceuticals within this age group. In the United States, approval has been granted for liraglutide and extended-release exenatide for pediatric patients aged ≥ 10 years with T2DM [30, 31]. Conversely, within the United Kingdom, sole approval is accorded to liraglutide; however, clinicians frequently opt for dulaglutide due to constraints on available alternatives [32]. In this context, our meta-analysis supports the efficacy and safety of GLP-1 receptor agonists, proffering viable therapeutic options for the amelioration and prevention of complications associated with pediatric T2DM.

Our meta-analysis exhibits certain limitations. The dearth of randomized controlled trials involving children, most of which have small sample sizes, may be attributed to the lower prevalence of T2DM in children than in adults, thereby compromising patient recruitment. There are more active randomized clinical trials that could contribute to the current knowledge of our topic; however, they have not published results yet. (NCT04596631, NCT00658021, NCT04873245). Additionally, throughout the data retrieval process, we encountered several challenges pertaining to the manner in which numerical data were reported in the articles encompassed within our study. This issue is particularly disconcerting, as the provision of clear, comprehensible, and reproducible data is imperative for informed clinical decision-making. This challenge is further exacerbated when dealing with small populations, necessitating the maximal utilization of available data. Furthermore, our study predominantly comprises females and Caucasians, whereas the disease predominantly affects indigenous and black populations [2, 33, 34]. To enhance the generalizability of the results, future studies should encompass more diverse populations with clear and accessible data. Such inclusivity is imperative for better informing clinical practice, especially when tending to vulnerable patients with a significant risk of comorbidities. Physicians rely heavily on this information to guide their clinical decisions.

In conclusion, this meta-analysis provides precise data pertaining to the efficacy and safety profile in children with T2DM. Within this specific population, GLP-1 RA exhibits a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and deemed tolerable.