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

Abstract

OBJECTIVETo evaluate whether LY2605541 results in lower fasting blood glucose (FBG) versus insulin glargine (GL).RESEARCH DESIGN AND METHODSThis 12-week, randomized, open-label, Phase 2 study enrolled patients with type 2 diabetes (hemoglobin A1c [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.RESULTSAt 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).CONCLUSIONSIn 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.

New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Oral Agents and Basal Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 2)

“…Differences of study design and populations preclude direct comparison of the present findings with other studies of longer-acting insulin. Nevertheless, these data resemble reported differences in hypoglycemia between degludec and glargine 100 units/mL (14) and those comparing PEGylated insulin lispro (LY2605541) and glargine 100 units/mL (15). Despite differences in treatment regimens, the results of EDITION 1 (basal and mealtime insulin) and EDITION 2 (basal insulin plus OADs) were consistent.…”

Lower Glucose Variability and Hypoglycemia Measured by Continuous Glucose Monitoring With Novel Long-Acting Insulin LY2605541 Versus Insulin Glargine

“…The observations of reduced glycemic variability with the CGM data are also consistent with the SMBG profiles of the clinical trial (15). The reduced glycemic variability may be hypothesized to result from the prolonged duration of action and flat profile previously demonstrated with LY2605541 compared with GL (13).…”

“…The between-day daytime SD was calculated for the SD of daily mean glucose between 0600 and 2400 h for each patient visit, and the within-day daytime SD was calculated between 0600 and 2400 h for each day and for each patient visit and then averaged across the available days for each patient. The term "between-day variability" as used in the present article and previously (15) corresponds to what has previously been designated as "standard deviation between daily means" (18,19). The area under the glucose curve (AUC) for the 24-h period was calculated as a measure of overall glycemic exposure.…”

“…A detailed description of the study design and results has been previously published (15). In brief, this randomized, open-label, multinational, parallel three-arm, phase II study was conducted to determine if LY2605541 treatment once daily in the morning reduced fasting blood glucose (FBG) by self-monitoring of blood glucose (SMBG) more than similarly administered GL.…”

LY2605541—A Preferential Hepato-Specific Insulin Analogue

“…Efficacy and safety of LY2605541 has been tested in two phase II studies (6,7). In a randomized 12-week open-label study in type 2 diabetic patients, once-daily basal insulin LY2605541 and insulin glargine were both administered in the morning (6).…”