BEGIN Flex T1.

Study characteristics
Methods	Design: parallel‐group RCT; non‐inferiority design; randomisation ratio: 1:1
Participants	Inclusion criteria: informed consent; males or females 18 years or more; T1DM for ≥ 12 months, the last 3 months with injection‐based therapies; current treatment with any basal insulin using one or two daily injections and no fewer than three injections with bolus insulin as mealtime bolus insulin therapy; HbA1c ≤ 10.0% by central laboratory analysis; BMI ≤ 35.0 kg/m2; ability to self‐manage insulin therapy as assessed by confirmation (verbal confirmation at screening visit) of a changed bolus insulin dose the preceding 2 months prior to screening; ability and willingness to adhere to the protocol, including performance of SMPG readings and self‐adjustment of insulin doses according to protocol Exclusion criteria: use within the last 3 months of any glucose‐lowering drug other than insulin; initiation or significant change of any systemic treatment which, in the investigator’s opinion, could interfere with glucose metabolism, such as systemic corticosteroids, beta‐blockers or monoamine oxidase inhibitors (inhaled corticosteroids were allowed); cardiovascular disease, within the last 6 months (defined as: stroke; decompensated heart failure NYHA class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty); uncontrolled treated/untreated severe hypertension (systolic BP ≥ 180 mmHg and/or diastolic BP ≥ 100 mmHg); impaired liver function, defined as ALAT ≥ 2.5 times upper limit of normal; impaired renal function defined as serum‐creatinine ≥ 180 µmol/L or 2.0 mg/dL; recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the investigator or hospitalisations for diabetic ketoacidosis during the previous 6 months; proliferative retinopathy or maculopathy requiring treatment, according to the investigator; pregnancy, breastfeeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements; cancer and medical history of cancer (except basal cell skin cancer or squamous cell skin cancer); any clinically significant disease or disorder, except for conditions associated with T1DM, which in the investigator’s opinion could interfere with the results of the study; mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding or co‐operation, including participants not able to read or write; previous participation in this study; known or suspected allergy to any of the study products or related products; receipt of any investigational drug within 1 month; donation of blood or participation in other trials within 1 month prior; known or suspected abuse of alcohol, narcotics, or illicit drugs Diagnostic criteria: clinically diagnosed (from CSR) Number of study centres: 71
Interventions	Intervention(s): degludec Comparator(s): glargine Duration of intervention: 26 weeks (52 weeks) Duration of follow‐up: 26 weeks (26 weeks) Run‐in period: none
Outcomes	Reported outcome(s) in full text of publication: adverse events, hypoglycaemia, glycaemic variables
Study registration	Trial identifier: NCT01079234, NN1250‐3770, WHO U1111‐1112‐8813, EudraCT Number 2009‐012923‐27 Study terminated early: no
Publication details	Language of publication: English Funding: commercial funding (Novo Nordisk) Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The aim of this trial is to investigate the efficacy and safety of NN1250 (insulin degludec) in participants with type 1 diabetes".
Notes	The participants were randomised to three intervention arms ‐ insulin degludec forced‐Flex, insulin degludec and insulin glargine. We have only included data from the insulin degludec and insulin glargine groups as they had identical titration regimens. The study consisted of a 26‐week main period and 26‐week extension period. Only data from the main period were included, as the two degludec groups were combined into one group in the extension period. Abstract revealed no additional data CSR and synopsis available. Data provided for all‐cause mortality, cardiovascular mortality, myocardial infarction, stroke, ketoacidosis, severe hypo/HbA1c combined Study also reported in FDA 2015 (FDA 2015) ‐ no additional data. No additional data from EMA 2012 (EMA 2012)