Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open­label, multinational, randomised, controlled, non-inferiority trial.

BACKGROUND: Insulin degludec (degludec) is a second-generation basal insulin with an improved pharmacokinetic-pharmacodynamic profile compared with first-generation basal insulins, but there are few data regarding its use during pregnancy. In this non-inferiority trial, we aimed to compare the efficacy and safety of degludec with insulin detemir (detemir), both in combination with insulin aspart (aspart), in pregnant women with type 1 diabetes. METHODS: This open-label, multinational, randomised, controlled, non-inferiority trial (EXPECT) was conducted at 56 sites (hospitals and medical centres) in 14 countries. Women aged at least 18 years with type 1 diabetes who were between gestational age 8 weeks (+0 days) and 13 weeks (+6 days) or planned to become pregnant were randomly assigned (1:1), via an interactive web response system, to degludec (100 U/mL) once daily or detemir (100 U/mL) once or twice daily, both with mealtime insulin aspart (100 U/mL), all via subcutaneous injection. Participants who were pregnant received the trial drug at randomisation, throughout pregnancy and until 28 days post-delivery (end of treatment). Participants not pregnant at randomisation initiated the trial drug before conception. The primary endpoint was the last planned HbA1c measurement before delivery (non-inferiority margin of 0·4% for degludec vs detemir). Secondary endpoints included efficacy, maternal safety, and pregnancy outcomes. The primary endpoint was assessed in all randomly assigned participants who were pregnant during the trial. Safety was assessed in all randomly assigned participants who were pregnant during the trial and exposed to at least one dose of trial drug. This study is registered with ClinicalTrials.gov, NCT03377699, and is now completed. FINDINGS: Between Nov 22, 2017, and Nov 8, 2019, from 296 women screened, 225 women were randomly assigned to degludec (n=111) or detemir (n=114). Mean HbA1c at pregnancy baseline was 6·6% (SD 0·6%; approximately 49 mmol/mol; SD 7 mmol/mol) in the degludec group and 6·5% (0·8%; approximately 48 mmol/mol; 9 mmol/mol) in the detemir group. Mean last planned HbA1c measurement before delivery was 6·2% (SE 0·07%; approximately 45 mmol/mol; SE 0·8 mmol/mol) in the degludec group and 6·3% (SE 0·07%; approximately 46 mmol/mol; SE 0·8 mmol/mol) in the detemir group (estimated treatment difference -0·11% [95% CI -0·31 to 0·08]; -1·2 mmol/mol [95% CI: -3·4 to 0·9]; pnon-inferiority<0·0001), confirming non-inferiority. Compared with detemir, no additional safety issues were observed with degludec. INTERPRETATION: In pregnant women with type 1 diabetes, degludec was found to be non-inferior to detemir. FUNDING: Novo Nordisk.

Inpatient hypoglycaemia: understanding who is at risk.

AIMS/HYPOTHESIS: We analysed data obtained from the electronic patient records of inpatients with diabetes admitted to a large university hospital to understand the prevalence and distribution of inpatient hypoglycaemia. METHODS: The study was conducted using electronic patient record data from Oxford University Hospitals NHS Foundation Trust. The dataset contains hospital admission data for patients coded for diabetes. We used the recently agreed definition for a level 1 hypoglycaemia episode as any blood glucose measurement <4 mmol/l and a level 2 hypoglycaemia episode as any blood glucose measurement <3 mmol/l. Any two or more consecutive low blood glucose measurements within a 2 h time window were considered as one single hypoglycaemic episode. RESULTS: We analysed data obtained from 17,658 inpatients with diabetes (1696 with type 1 diabetes, 14,006 with type 2 diabetes, and 1956 with other forms of diabetes; 9277 men; mean ± SD age, 66 ± 18 years) who underwent 32,758 hospital admissions between July 2014 and August 2018. The incidence of level 1 hypoglycaemia was 21.5% and the incidence of level 2 hypoglycaemia was 9.6%. Recurrent level 1 and level 2 hypoglycaemia occurred, respectively, in 51% and 39% of hospital admissions in people with type 2 diabetes with at least one hypoglycaemic episode, and in 55% and 45% in those with type 1 diabetes. The incidence of level 2 hypoglycaemia in people with type 2 diabetes, when corrected for the number of people who remained in hospital, remained constant for the first 100 h at approximately 0.15 events per h per admission. With regards to the hypoglycaemia distribution during the day, after correcting for the number of blood glucose tests per h, there were two clear spikes in the rate of hypoglycaemia approximately 3 h after lunch and after dinner. The highest rate of hypoglycaemia per glucose test was seen between 01:00 hours and 05:00 hours. Medication had a significant impact on the incidence of level 2 hypoglycaemia, ranging from 1.5% in people with type 2 diabetes on metformin alone to 33% in people treated with a combination of rapid-acting insulin analogue, long-acting insulin analogue and i.v.-administered insulin. CONCLUSIONS/INTERPRETATION: Retrospective analysis of data from electronic patient records enables clinicians to gain a greater understanding of the incidence and distribution of inpatient hypoglycaemia. This information should be used to drive evidence-based improvements in the glycaemic control of inpatients through targeted medication adjustment for specific populations at high risk of hypoglycaemia.