title: Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with Type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin.
  
  
  METHODS
  In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l.
  
  
  RESULTS
  The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed.
  
  
  CONCLUSIONS
  Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.
authors.affiliation: Mossakowski Medical Research Centre, Polish Academy of Sciences and Department of Internal Diseases, Endocrinology and Diabetology, Central Clinical Hospital MSW, Warsaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Franek
authors.affiliation: Third Department of Medicine, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Haluzík
authors.affiliation: Clinical Hospital Center Osijek, Osijek, Croatia.
authors.forename: S
authors.initials: S
authors.lastname: Canecki Varžić
authors.affiliation: Kartal Training and Research Hospital, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Sargin
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Macura
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Zacho
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
mesh_terms: D000368:Aged; D061265:Biphasic Insulins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D015190:Blood Glucose Self-Monitoring; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D016903:Drug Monitoring; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D062407:Meals; D008875:Middle Aged; D012306:Risk; D012720:Severity of Illness Index; D012995:Solubility
chemical_list: D061265:Biphasic Insulins; D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C557564:insulin aspart, insulin aspart protamine drug combination 30:70; C578220:insulin degludec, insulin aspart drug combination