title: Insulin degludec/insulin aspart once daily in Type 2 diabetes: a comparison of simple or stepwise titration algorithms (BOOST®: SIMPLE USE).
abstract: To compare the efficacy and safety of two titration algorithms for insulin degludec/insulin aspart (IDegAsp) administered once daily with metformin in participants with insulin-naïve Type 2 diabetes mellitus.
  
  
  
  This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA1c(%) after 26 weeks.
  
  
  
  Change in HbA1cat Week 26 was IDegAspSimple-14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAspStepwise-11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAspSimpleto IDegAspStepwise(non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAspStepwise[2.1 per patient years of exposure (PYE)] vs. IDegAspSimple(3.3 PYE) (estimated rate ratio IDegAspSimple/IDegAspStepwise1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported.
  
  
  
  In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAspSimpletitration algorithm improved HbA1clevels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm.
authors.affiliation: Kangbuk Samsung Hospital, Seoul, Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Park
authors.affiliation: Universiti Sains Malaysia Health Campus USM, Kelantan, Malaysia.
authors.forename: W M W
authors.initials: WM
authors.lastname: Bebakar
authors.affiliation: Endocrinology Service, Hospital Universitario 'Dr José E. González', Monterrey, México.
authors.forename: P G
authors.initials: PG
authors.lastname: Hernandez
authors.affiliation: Medical Affairs, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Macura
authors.affiliation: Medical & Science, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: M L
authors.initials: ML
authors.lastname: Hersløv
authors.affiliation: Four Rivers Clinical Research, Paducah, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: de la Rosa
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D008687:Metformin; C517652:hemoglobin A1c protein, human; C578220:insulin degludec, insulin aspart drug combination