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Aim To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions. Materials and Methods For this single‐centre, double‐blind, randomized, placebo‐controlled, cross‐over trial, non‐obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9‐10 mmol/L). For safety evaluation, ß‐hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured. Results Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 ± 0.7 vs. 7.3 ± 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% ± 6.0% vs 3.1% ± 5.2%; P = .75). Urinary glucose excretion was increased 3‐fold using dapagliflozin (149 ± 42 vs. 49 ± 23 g/24 hours) with a total insulin reduction of 22% (39.7 ± 12.7 vs. 30.6 ± 10.4 U; P = .004). No abnormal elevated BHB values were observed. Conclusions In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.

Background Dasiglucagon, a next‐generation, ready‐to‐use aqueous glucagon analog formulation, has been developed to treat severe hypoglycemia in individuals with diabetes. Objective The aim of this trial was to evaluate the safety and efficacy of dasiglucagon in pediatric individuals with type 1 diabetes (T1DM). Participants were children and adolescents (6–17 years) with T1DM. Methods In this randomized double‐blind trial, 42 participants were randomly allocated (2:1:1) to a single subcutaneous (SC) injection of dasiglucagon (0.6 mg), placebo, or reconstituted glucagon (GlucaGen; dosed per label) during insulin‐induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery (first PG increase ≥20 mg/dL after treatment initiation without rescue intravenous glucose). The primary comparison was dasiglucagon vs. placebo; glucagon acted as a reference. Results The median time (95% confidence interval) to PG recovery following SC injection was 10 min (8–12) for dasiglucagon vs. 30 min (20 to –) for placebo ( P < .001); the median time for glucagon was 10 min (8–12), which did not include the time taken to reconstitute the lyophilized powder. PG recovery was achieved in all participants in the dasiglucagon and glucagon groups within 20 min of dosing compared to 2 out of 11 patients (18%) with placebo. The most frequent adverse events were nausea and vomiting, as expected with glucagon treatment. Conclusions Consistent with adult phase 3 trials, dasiglucagon rapidly and effectively restored PG levels following insulin‐induced hypoglycemia in children and adolescents with T1DM, with an overall safety profile similar to glucagon.

Primary prevention of type 1 diabetes (T1D) requires intervention in genetically at‐risk infants. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD‐02, that identifies infants with a genetic high risk of T1D, enrolls these into primary prevention trials, and follows the children for beta‐cell autoantibodies and diabetes. Genetic testing is offered either at delivery, together with the regular newborn testing, or at a newborn health care visits before the age of 5 months in regions of Germany (Bavaria, Saxony, Lower Saxony), UK (Oxford), Poland (Warsaw), Belgium (Leuven), and Sweden (Region Skåne). Seven clinical centers will screen around 330 000 infants. Using a genetic score based on 46 T1D susceptibility single‐nucleotide polymorphisms (SNPs) or three SNPS and a first‐degree family history for T1D, infants with a high (>10%) genetic risk for developing multiple beta‐cell autoantibodies by the age of 6 years are identified. Screening from October 2017 to December 2018 was performed in 50 669 infants. The prevalence of high genetic risk for T1D in these infants was 1.1%. Infants with high genetic risk for T1D are followed up and offered to participate in a randomized controlled trial aiming to prevent beta‐cell autoimmunity and T1D by tolerance induction with oral insulin. The GPPAD‐02 study provides a unique path to primary prevention of beta‐cell autoimmunity in the general population. The eventual benefit to the community, if successful, will be a reduction in the number of children developing beta‐cell autoimmunity and T1D.