title: Therapy after single oral agent failure: adding a second oral agent or an insulin mixture?
abstract: OBJECTIVE
  to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily plus metformin (Mix25+M) with glibenclamide plus metformin (G+M), in patients with type 2 diabetes inadequately controlled with a single oral agent.
  
  
  METHODS
  597 patients treated in a randomized, open-label, 16-week parallel study. Variables evaluated: hemoglobin A1C (A1C), patient symptoms, hypoglycemia rate (episodes/patient/30 days), and incidence (% patients experiencing > or =1 episode). For a subset of patients (N=120), fasting, 1-h, and 2-h postprandial plasma glucose (FPG, 1-h ppPG, 2-h ppPG) in response to a standardized test meal (STM) and self-monitored blood glucose (BG) profiles were measured.
  
  
  RESULTS
  improved A1C at endpoint for both groups, and A1C changes from baseline to endpoint were not significantly different between treatments (Mix25+M, -1.87+/-1.35% vs. G+M, -1.98+/-1.28%; p=0.288). Among patients completing STM; endpoint 2-h ppPG was significantly lower with Mix25+M (9.05+/-3.32 mmol/l vs. 12.31+/-3.65 mmol/l; p<0.001), as was 2-h ppPG excursion (2-h ppPGex)(0.38+/-3.23 mmol/l vs. 2.88+/-1.98 mmol/l; p<0.001). Percentage of patients achieving postprandial BG targets (<10 mmol/l) at endpoint was significantly greater with Mix25+M (80% vs. 48%; p<0.001). Although, overall hypoglycemia rates were similar, percentage of patients experiencing and rate of nocturnal hypoglycemia was less with Mix25+M (1% vs. 5%; p<0.01, and 0.01 vs. 0.08 episodes/pt/30 d; p=0.007). Patients reported less polyuria with Mix25+M (p<0.001).
  
  
  CONCLUSIONS
  in patients with type 2 diabetes failing on metformin or a sulfonylurea, Mix25+M provided similar overall glycemic control, lower ppPG, reduced nocturnal hypoglycemia, and fewer hyperglycemic symptoms compared to G+M.
authors: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. jkmalone@lilly.com
authors: James K
authors: JK
authors: Malone
authors: Scott D
authors: SD
authors: Beattie
authors: Barbara N
authors: BN
authors: Campaigne
authors: Patricia A
authors: PA
authors: Johnson
authors: Andrew S
authors: AS
authors: Howard
authors: Zvonko
authors: Z
authors: Milicevic
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D017060:Patient Satisfaction; D044469:Racial Groups; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds