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.

Associaçäo do droperidol e morfina por via peridural: avaliaçäo da analgesia e da profilaxia dos efeitos colaterais da morfina / Droperidol and morphine epidural: assessment of analgesia and side effects prophylaxis morphine

JUstificativa e objetivos: a morfina, administrada por via peridural, tem sido eficaz no controle de dor no período pós-operatório imediato, entretanto causa efeitos colaterais. O objetivo deste estudo foi avalir o efeito, no período pós-operatório imediato, do uso do droperidol associado a morfina por via peridural em relaçäo a sonolência, prurido, náuseas, vômitos e a analgesia. Método: trinta pacientes submetidas à cirurgia ginecológica eletiva por via abdominal receberam anestesia geral associada a analgesia peridural. As pacientes foram aleatoriamente distribuídas em dois grupos: no grupo M administrou-se, por via peridural, morfina 3mg (3ml) e soluçäo fisiológica (7ml). No grupo MD administrou-se pela mesma via, morfina 3mg (3ml) e droperidol 2,5 mg (1ml) e soluçäo fisiológica (6ml). A anestesia geral foi induzida com etomidato, alfentanil e pancurônio e mantida com isoflurano e alfentanil. O efeito do droperidol foi avaliado na sexta e vigésima quarta hora após a punçäo peridural, de acordo com a presença ou ausência de dor, sedaçäo, prurido, náuseas e vômitos. Resultados: os resultados näo mostraram diferença significante em relaçäo a idade e ao peso das pacientes nos grupos estudados (p<-0,05). Quando se utilizou o droperidol peridural houve melhora da qualidade e duraçäo da analgesia nas primeiras 6 horas do período pós-operatório. Näo houve diferença significante entre os grupos M e MD em relaçäo a incidência de prurido, náuseas e vômitos. Conclusöes: o droperidol na dose de 2,5mg por via peridural aumenta a sonolência das pacientes nas primeiras 6 horas do período pós-operatório e a presença de analgesia nas primeiras 24 horas. Näo houve reduçäo significante dos efeitos colaterais da morfina por esta via