## 4 Discussion  
People with T1 DM require lifelong glucose monitoring and insulin replacement therapy, and several technological devices have been developed over the last decades to help them in the self-management of this disease, such as insulin pumps or continuous glucose monitoring devices [1; 12]. The AP is the latest evolution of these technologies, with the main aim of enabling a fully closed-loop system to provide a completely automatized insulin administration, mimicking the biological pancreas [12]. However, current closed-loop systems still require that users enter the carbohydrate content of upcoming meals to determine the adequate dosing of pre-prandial insulin [6]. The incorporation of pramlintide within the AP system could help to delay mealtime insulin requirements by delaying gastric emptying, suppressing nutrient-stimulated glucagon secretion and increasing [18]. This may be of particular interest to those patients who do not achieve the expected clinical results with conventional insulin therapy. The results of this review show that the scientific evidence on the efficacy and safety of this device is still very scarce, consisting of four small studies carried out in a 24-h inpatient setting (except one of them, with an outpatient follow up of 12 days but only 4 patients) by the same research group. [PERSON] et al. (2020) [8] found that the dual system \begin{table}
\begin{tabular}{l l} \hline \hline \multicolumn{2}{c}{**Adverse Events**} \\ \hline \hline  & RAI: 11 hypoglycemic episodes (HE) requiring oral treatment (1 HE every 2.5 d); gastrointestinal symptoms (GIS) 0\% after (0 of 112) meals). \\  & RAI + PR: 12 HE (1 HE every 2.3 d); GIS: 6\% (6 out of 108 meals); 3 mild \\  & and 3 moderate, all were transient. \\  & REGI + PR: 18 HE (1 HE every 1.4 d); GIS: 11\% (11 of 104 meals); 2 mild, \\  & 6 moderate and 3 moderate to severe. \\  & There were no elevated ketones (>18 mg/dl) in any administration of \\  & the artificial pancreas; non-inferiority contrast \\ \hline \hline  & 8 participants (33\%) had at least one hypoglycemia event (<60 mg/dL) \\  & with the closed artificial pancreas vs. 14 (58\%) participants with the \\  & hybrid system; \\  & 3 participants (13\%) reported non-mild nausea and 1 participant (4\%) \\  & with non-mild bloating with the artificial pancreas closed; no \\  & participant presented these events in the hybrid system. \\ \hline \hline  & Feasibility study: \\  & RAI + PR with SMA: 3 participants experienced gastrointestinal symptoms. \\  & Pilot study: Frequency and severity of gastrointestinal symptoms \\  & measured with a Likert scale from 1 to 6: \\  & FIASP + placebo (CC) \\  & Frequency: 1.1 \(\pm\) 0.4 \\  & Severity: 1.0 \(\pm\) 0.2 \\  & FIASP + PR (SMA): \\  & Frequency: 1.3 \(\pm\) 0.7 \\  & Severity: 1.3 \(\pm\) 0.6 \\  & 1 participant reported moderate abdominal pain \\  & FIASP + placebo con (SMA): \\  & Frequency: 1.3 \(\pm\) 0.5 \\  & Severity: 1.3 \(\pm\) 0.6 \\  & 1 participant reported moderate abdominal pain and moderate nausea. \\ \hline \hline \end{tabular} HE: hypoglycemic episodes; GIS: gastrointestinal symptoms; CC: carbohydrate counting; SMA: simple meal announcement; PR: pramlintide; d: days; FiASP: faster-acting insulin aspart.  
\end{table} 
Table 4: Adverse events observed among the included studies. outperformed the insulin-alone system when both were applied along CC, while the results of [PERSON] et al. (2021b) [25] showed that the fully closed-loop dual system (without CC or SMA), although showed non-inferiority in time in therapeutic glucose range compared to the insulin-alone system with CC, obtained significantly worse outcomes during the daytime (relative increase of 57% of time above 180 mg/dL). When the dual system was accompanied by SMA in the two studies of [PERSON] et al. (2021) [24], results were very similar to that obtained by the insulin-alone system with CC. Regarding safety, the three studies showed gastrointestinal adverse effects associated with the dual system, although they were non-serious in all cases.