title: Comparison of biphasic insulin aspart 30 given three times daily or twice daily in combination with metformin versus oral antidiabetic drugs alone in patients with poorly controlled type 2 diabetes: a 16-week, randomized, open-label, parallel-group trial conducted in russia.
abstract: BACKGROUND
  Modern premixed insulins offer a flexible approach to the initiation of insulin therapy in patients with poorly controlled type 2 diabetes. A disadvantage of twice-daily regimens of biphasic insulin aspart 30 (BIAsp 30) is that lunchtime control (when no insulin is administered) can be suboptimal. Therefore, it is possible that administering BIAsp 30 thrice daily might further optimize glycemic control and offer an option for patients in whom metformin (MET) is contraindicated.
  
  
  OBJECTIVE
  This study evaluated the efficacy and safety profiles of 2 different regimens of BIAsp 30 compared with a regimen consisting of oral antidiabetic drugs (OADs) alone.
  
  
  METHODS
  In this multicenter, randomized, open-label, parallel-group trial, insulin-naive patients with poorly controlled type 2 diabetes (baseline glycosylated hemoglobin [HbA(1c) > or =8.0%) who were taking OADs (a sulfonylurea or meglitinide with/without MET or MET only) were randomized to receive BIAsp 30 TID, BIAsp 30 BID + MET, or continuation of their current OAD therapy for 16 weeks. The primary end point was HbA(1c) at the end of the study. Secondary end points included reductions in HbA(1c), mean blood glucose (BG), prandial increment, mean 7-point self-monitored BG profile, weight changes, tolerability (hypoglycemia, adverse events), and satisfaction/quality of life (derived from 2 questionnaires completed at weeks 0, 8, and 16).
  
  
  RESULTS
  The study enrolled 308 insulin-naive patients with type 2 diabetes (78.9% female; mean age, 58.3 years; body mass index, 29.4 kg/m(2); HbA(1c), 10.3%). Both BIAsp 30 TID and BIAsp 30 BID + MET were associated with significantly greater mean (SD) reductions in HbA(1c) relative to OADs alone (absolute percent reduction: 2.9% [1.5%], 3.0% [1.6%], and 2.1% [1.4%], respectively; P < 0.001, both insulin groups vs OAD group) and improved post-prandial glucose control (reduction in mean post-prandial glucose:-6.32 [4.07], -6.44 [4.70], and -3.59 [4.22] mmol/L; P < 0.001, both insulin groups vs OAD group). The mean decrease in the prandial increment was -1.26 mmol/L for BIAsp 30 TID, -2.15 mmol/L for BIAsp 30 BID + MET, and -0.44 mmol/L for OAD. The differences in reduction in the prandial increment were statistically significant for BIAsp 30 TID versus OAD (P = 0.047), BIAsp 30 BID + MET versus OAD (P < 0.001), and BIAsp 30 TID versus BIAsp 30 BID + MET (P = 0.042). Mean body weight increased significantly from baseline with both BIAsp 30 TID and BIAsp 30 BID + MET (+1.71 and +1.50 kg, respectively; both, P < 0.001), and decreased significantly in the OAD group (-0.75 kg; P = 0.003). There were no major hypoglycemic events, and most hypoglycemic events were recorded as symptoms only (144/158 [91.1%]). There were no significant differences in the mean frequency of overall hypoglycemic episodes between BIAsp 30 TID and BIAsp 30 BID + MET (0.73 and 0.69 episodes per patient-year, respectively).
  
  
  CONCLUSIONS
  In these patients with type 2 diabetes that was poorly controlled by OADs, BIAsp 30 TID and BIAsp 30 BID plus MET were associated with significantly greater reductions in HbA(1c) and postprandial BG compared with OADs alone. The insulin regimens were associated with significantly more weight gain than OADs alone. There were no differences in rates of hypoglycemia between the insulin regimens.
authors.affiliation: Department of Prophylactic Medicine, Post-graduate Medical Education Institute, Khabarovsk, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Ushakova
authors.forename: Vera
authors.initials: V
authors.lastname: Sokolovskaya
authors.forename: Alla
authors.initials: A
authors.lastname: Morozova
authors.forename: Farida
authors.initials: F
authors.lastname: Valeeva
authors.forename: Olga
authors.initials: O
authors.lastname: Zanozina
authors.forename: Olga
authors.initials: O
authors.lastname: Sazonova
authors.forename: Elena
authors.initials: E
authors.lastname: Zhadanova
authors.forename: Maria
authors.initials: M
authors.lastname: Starceva
authors.forename: Elena
authors.initials: E
authors.lastname: Kazakova
authors.forename: Marina
authors.initials: M
authors.lastname: Saifullina
authors.forename: Irina
authors.initials: I
authors.lastname: Shapiro
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarasov
authors.forename: Bassam
authors.initials: B
authors.lastname: Al-Tayar
authors.forename: Ninella
authors.initials: N
authors.lastname: Starkova
mesh_terms: D015415:Biomarkers; D061265:Biphasic Insulins; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011788:Quality of Life; D012426:Russia; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015415:Biomarkers; D061265:Biphasic Insulins; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008687:Metformin; C557564:insulin aspart, insulin aspart protamine drug combination 30:70