Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial.

AIMS/HYPOTHESIS: This study compared the frequency of hypoglycaemia, time to hypoglycaemia and recovery from hypoglycaemia after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100. Furthermore, the symptomatic and counterregulatory responses to hypoglycaemia were compared between icodec and glargine U100 treatment. METHODS: In a randomised, single-centre (Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria), open-label, two-period crossover trial, individuals with type 2 diabetes (age 18-72 years, BMI 18.5-37.9 kg/m2, HbA1c ≤75 mmol/mol [≤9.0%]) treated with basal insulin with or without oral glucose-lowering drugs received once-weekly icodec (for 6 weeks) and once-daily glargine U100 (for 11 days). Total weekly doses were equimolar based on individual titration of daily glargine U100 during the run-in period (target fasting plasma glucose [PG]: 4.4-7.2 mmol/l). Randomisation was carried out by assigning a randomisation number to each participant in ascending order, which encoded to one of two treatment sequences via a randomisation list prepared prior to the start of the trial. At steady state, double and triple doses of icodec and glargine U100 were administered followed by hypoglycaemia induction: first, euglycaemia was maintained at 5.5 mmol/l by variable i.v. infusion of glucose; glucose infusion was then terminated, allowing PG to decrease to no less than 2.5 mmol/l (target PGnadir). The PGnadir was maintained for 15 min. Euglycaemia was restored by constant i.v. glucose (5.5 mg kg-1 min-1). Hypoglycaemic symptoms score (HSS), counterregulatory hormones, vital signs and cognitive function were assessed at predefined PG levels towards the PGnadir. RESULTS: Hypoglycaemia induction was initiated in 43 and 42 participants after double dose of icodec and glargine U100, respectively, and in 38 and 40 participants after triple doses, respectively. Clinically significant hypoglycaemia, defined as PGnadir <3.0 mmol/l, occurred in comparable proportions of individuals treated with icodec vs glargine U100 after double (17 [39.5%] vs 15 [35.7%]; p=0.63) and triple (20 [52.6%] vs 28 [70.0%]; p=0.14) doses. No statistically significant treatment differences were observed in the time to decline from PG values of 5.5 mmol/l to 3.0 mmol/l (2.9-4.5 h after double dose and 2.2-2.4 h after triple dose of the insulin products). The proportion of participants with PGnadir ≤2.5 mmol/l was comparable between treatments after double dose (2 [4.7%] for icodec vs 3 [7.1%] for glargine U100; p=0.63) but higher for glargine U100 after triple dose (1 [2.6%] vs 10 [25.0%]; p=0.03). Recovery from hypoglycaemia by constant i.v. glucose infusion took <30 min for all treatments. Analyses of the physiological response to hypoglycaemia only included data from participants with PGnadir <3.0 mmol/l and/or the presence of hypoglycaemic symptoms; in total 20 (46.5%) and 19 (45.2%) individuals were included after a double dose of icodec and glargine U100, respectively, and 20 (52.6%) and 29 (72.5%) individuals were included after a triple dose of icodec and glargine U100, respectively. All counterregulatory hormones (glucagon, adrenaline [epinephrine], noradrenaline [norepinephrine], cortisol and growth hormone) increased during hypoglycaemia induction with both insulin products at both doses. Following triple doses, the hormone response was greater with icodec vs glargine U100 for adrenaline at PG3.0 mmol/l (treatment ratio 2.54 [95% CI 1.69, 3.82]; p<0.001), and cortisol at PG3.0 mmol/l (treatment ratio 1.64 [95% CI 1.13, 2.38]; p=0.01) and PGnadir (treatment ratio 1.80 [95% CI 1.09, 2.97]; p=0.02). There were no statistically significant treatment differences in the HSS, vital signs and cognitive function. CONCLUSIONS/INTERPRETATION: Double or triple doses of once-weekly icodec lead to a similar risk of hypoglycaemia compared with double or triple doses of once-daily glargine U100. During hypoglycaemia, comparable symptomatic and moderately greater endocrine responses are elicited by icodec vs glargine U100. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945656. FUNDING: This study was funded by Novo Nordisk A/S.

Quality of teamwork in multidisciplinary cancer team meetings: A feasibility study.

BACKGROUND: Tumor boards (TB) play an important role to formulate a management plan for the treatment of patients with a malignancy. Recent evidence suggests that optimally functioning teams (teamwork, communication and decision making) are major prerequisites to conduct efficient TB meetings. The aims of this study were i) to use a readily published tool as a template for the development of a teamwork perspective extended assessment tool and ii) to evaluate the tool in a feasibility study by clinical and non-clinical observers. METHODS: A systematic literature search in four databases revealed the "Metric for the Observation of Decision-making (MODe)" to be consistently used. MODe served as a template for the clinical evaluation, additional, notably teamwork items were integrated, and the resulting tool was tested in a feasibility study in TBs by clinical and non-clinical observers. The percentage of agreement between observers was assessed in a two-step approach: first, agreement of raters on discussion of items by TB members, and second, agreement of raters based on ordinal scale. RESULTS: In total, 244 patients were discussed in 27 TB sessions, thereof 136 (56%) fast track cases and 108 (44%) complex cases. In 228 (93%) of all cases an agreement for recommendation of a treatment plan was reached. Observers showed in general high agreement on discussion of the items. For the majority of items, the percentage of agreement between the different pairs of rater was similar and mostly high. CONCLUSION: A newly developed TB team performance tool using MODe as a template was piloted in a German-speaking country and enabled the assessment of specialized multidisciplinary teams with a special focus on teamwork patterns. The developed assessment tool requires evaluation in a larger collective for validation, and additional assessment whether it can be applied equally by non-clinicians and clinicians.