A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes.
OBJECTIVE
To evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL).


METHODS
This 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A(1c) [A1C] ≤ 10.5%), taking metformin and/or sulfonylurea with GL or NPH insulin once daily. Patients converted to morning insulin administration during lead-in were randomized 2:1 from GL (n = 248) or NPH insulin (n = 39) to LY2605541 (n = 195) or GL (n = 95) once daily in the morning.


RESULTS
At 12 weeks, FBG (mean ± SE) was similar with LY2605541 and GL (118.2 ± 2.0 mg/dL [6.6 ± 0.1 mmol/L] vs. 116.9 ± 2.7 mg/dL [6.5 ± 0.2 mmol/L], P = 0.433) as was A1C (7.0 ± 0.1 vs. 7.2 ± 0.1%, P = 0.279). Intraday blood glucose variability was reduced with LY2605541 (34.4 vs. 39.1 mg/dL [1.9 vs. 2.2 mmol/L], P = 0.031). LY2605541 patients had weight loss (-0.6 ± 0.2 kg, P = 0.007), whereas GL patients gained weight (0.3 ± 0.2 kg, P = 0.662; treatment difference: -0.8 kg, P = 0.001). The incidence and rate of both total hypoglycemia and nocturnal hypoglycemia were comparable between LY2605541 and GL, although, LY2605541 had a 48% reduction in nocturnal hypoglycemia after adjusting for baseline hypoglycemia (P = 0.021). Adverse events were similar across treatments. Alanine aminotransferase and aspartate aminotransferase remained within normal range but were significantly higher with LY2605541 (P ≤ 0.001).


CONCLUSIONS
In patients with type 2 diabetes, LY2605541 and GL had comparable glucose control and total hypoglycemia rates, but LY2605541 showed reduced intraday variability, lower nocturnal hypoglycemia, and weight loss relative to GL.
International Diabetes Center at Park Nicollet, Minneapolis, MN, USA.
Richard M
RM
Bergenstal
Julio
J
Rosenstock
Richard F
RF
Arakaki
Melvin J
MJ
Prince
Yongming
Y
Qu
Vikram P
VP
Sinha
Daniel C
DC
Howey
Scott J
SJ
Jacober
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D011092:Polyethylene Glycols; C587357:LY2605541