Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018–2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. Overall, 156 patients (mean age 68 years, 64.1

Young age onset and long-life expectancy of type 1 diabetes mellitus (T1DM) people make it essential to achieve an early, stable and optimal glycemic control to prevent chronic complications and ensure good quality of life. These goals can only be achieved by having a healthcare organization that guarantees patient equity of access, quality and continuity of care, with an appropriate use of resources. To make the treatment organization efficient and appropriate, various health systems have implemented Diagnostic Therapeutic Assistance Paths (DTAP). DTAPs aim to share decision-making processes and healthcare organization for specific groups of patients on the basis of existing guidelines and in relation to the available resources, during a well-defined period of time. In Italy, the Italian Association of Diabetologists (AMD) scientific society, in association with Association of Pediatric Endocrinologists and Diabetologists (SIEDP), and voluntary diabetes associations (i.e. Diabetes Italia) developed a national DTAP for T1DM. Five DTAP models were defined, focusing on 5 different disease stages or treatment process: onset of illness or first referral from another diabetes clinic, routine visit in good metabolic control, uncontrolled hyperglycemia, advanced technologies, transition from pediatric to adult diabetes clinic. Objectives, healthcare professionals involved, visits organization, and educational contents for each of these PDTAs are detailed in the core document. This DTAP will be disseminated through the AMD regional referents to the Regional Healthcare Systems. Each Region will be asked to implement the DTAP through multi-professional working groups, with the participation of regional AMD referents and representatives of Patient Associations. The DTAP effectiveness will be evaluated using an indicators’ system every year.

AIM OF THE STUDY Sodium-glucose cotransport inhibitors (SGLT-i) improve glycemic control in patients with type 1 diabetes (T1DM). However, their use is associated with an increased risk of diabetic ketoacidosis (DKA). Aim of this study was to evaluate the off-label prescription of these drugs to patients with T1DM. MATERIALS AND METHODS From 2018/08/21 to 2019/04/03 AMD invited members to complete a survey on the off-label prescription of SGLT2 inhibitors (SGLT2i) to patients with T1DM. RESULTS N = 161 specialists completed the survey; 72 (44.7%) had prescribed SGLT2i for T1DM patients. Prescribing and non-prescribing specialists were similar for years in practice and type of outpatient facility. Specialists from Northern Italy or caring for ≥50 T1DM patients were more likely to prescribe SGLT2i to their patients. Specialists prescribed SGLT2i mainly to T1DM patients on multiple daily insulin injection. The most frequent reasons for SGLT2i prescription were to improve suboptimal glycemic control, facilitate weight loss and reduce insulin requirement. Only 48% of specialists required patients to sign an informed consent for the off-label prescription.Twenty-five percent of specialists omitted to prescribe strips for ketonuria/ketonemia and only 26% recommended to measure ketones when glucose levels exceeded 200 mg/dl. All specialists recommended avoiding dehydration and prolonged fasting when using SGLT2i, but only 23% reviewed the symptoms of ketosis and only 9.7% offered patients the six expert recommendations for mitigating the risk of DKA. Nearly 20% of specialists who prescribed SGLT2i to T1DM women of childbearing age omitted to inform them of the risks for conception, and only 12.5% provided patients with the four recommendations that should be given when prescribing drugs not authorized in pregnancy. CONCLUSIONS The results of this survey document the need to improve the awareness of professionals and patients about the risks of DKA and risk mitigation when SGLT2i are prescribed to T1DM patients. KEY WORDS SGLT inhibitors; type 1 diabetes; diabetic ketosis/ketoacidosis; off-label prescription.

SummaryReview of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear.It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively.TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P=0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P=0.0156 and P=0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis.Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.