title: The study of once- and twice-daily biphasic insulin aspart 30 (BIAsp 30) with sitagliptin, and twice-daily BIAsp 30 without sitagliptin, in patients with type 2 diabetes uncontrolled on sitagliptin and metformin-The Sit2Mix trial.
abstract: OBJECTIVE
  Investigate efficacy and tolerability of intensifying diabetes treatment with once- or twice-daily biphasic insulin aspart 30 (BIAsp 30) added to sitagliptin, and twice-daily BIAsp 30 without sitagliptin in patients with type 2 diabetes (T2D) inadequately controlled on sitagliptin.
  
  
  METHODS
  Open-label, three-arm, 24-week trial; 582 insulin-naïve patients were randomized to twice-daily BIAsp 30+sitagliptin (BIAsp BID+Sit), once-daily BIAsp 30+sitagliptin (BIAsp QD+Sit) or twice-daily BIAsp 30 without sitagliptin (BIAsp BID), all with metformin.
  
  
  RESULTS
  After 24 weeks, HbA1c reduction (%) was superior with BIAsp BID+Sit vs. BIAsp QD+Sit (BIAsp BID+Sit minus BIAsp QD+Sit difference: -0.36 [95% CI -0.54; -0.17], P<0.001) and BIAsp BID (BIAsp BID minus BIAsp BID+Sit difference: 0.24 [0.06; 0.43], P=0.01). Observed final HbA1c values were 6.9%, 7.2% and 7.1% (baseline 8.4%), and 59.8%, 46.5% and 49.7% of patients achieved HbA1c <7.0%, respectively. Confirmed hypoglycaemia was lower with BIAsp QD+Sit vs. BIAsp BID (P=0.015); rate: 1.17 (BIAsp QD+Sit), 1.50 (BIAsp BID+Sit) and 2.24 (BIAsp BID) episodes/patient-year. Difference in bodyweight change favoured BIAsp QD+Sit vs. both BID groups (P<0.001).
  
  
  CONCLUSIONS
  Adding BIAsp 30 to patients with T2D poorly controlled with sitagliptin and metformin is efficacious and well tolerated; however, while BIAsp BID+Sit showed superior glycaemic control, BIAsp QD+Sit had a lower rate of hypoglycaemia and showed no weight gain.
authors.affiliation: Coffs Endocrine and Diabetes Services, Coffs Harbour, New South Wales, Australia. Electronic address: solinjawi@hotmail.com.
authors.forename: Sultan
authors.initials: S
authors.lastname: Linjawi
authors.affiliation: Columbia Asia Hospital, Seremban, Malaysia.
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Sothiratnam
authors.affiliation: Akdeniz University, School of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Antalya, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Sari
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Andersen
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Line Conradsen
authors.initials: LC
authors.lastname: Hiort
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Paturi
authors.initials: P
authors.lastname: Rao
mesh_terms: D000368:Aged; D001208:Asia; D001315:Australia; D015415:Biomarkers / Q000097:blood; D061265:Biphasic Insulins / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003362:Cost-Benefit Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics; D004334:Drug Administration Schedule; D016527:Drug Costs; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D013020:South America; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D061265:Biphasic Insulins; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008687:Metformin; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human; C557564:insulin aspart, insulin aspart protamine drug combination 30:70
keywords: Biphasic insulin; Randomized trial; Sitagliptin; Type 2 diabetes