Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: a randomized, crossover study

Julio Rosenstock, Richard M Bergenstal, Thomas C Blevins, Linda A Morrow, Melvin J Prince, Yongming Qu, Vikram P Sinha, Daniel C Howey, Scott J Jacober, Julio Rosenstock, Richard M Bergenstal, Thomas C Blevins, Linda A Morrow, Melvin J Prince, Yongming Qu, Vikram P Sinha, Daniel C Howey, Scott J Jacober

Abstract

OBJECTIVE To compare effects of LY2605541 versus insulin glargine on daily mean blood glucose as part of a basal-bolus regimen for type 1 diabetes. RESEARCH DESIGN AND METHODS In this randomized, Phase 2, open-label, 2 × 2 crossover study, 137 patients received once-daily basal insulin (LY2605541 or glargine) plus mealtime insulin for 8 weeks, followed by crossover treatment for 8 weeks. Daily mean blood glucose was obtained from 8-point self-monitored blood glucose profiles. The noninferiority margin was 10.8 mg/dL. RESULTS LY2605541 met noninferiority and superiority criteria compared with insulin glargine in daily mean blood glucose (144.2 vs. 151.7 mg/dL, least squares mean difference = -9.9 mg/dL [90% CI -14.6 to -5.2], P < 0.001). Fasting blood glucose variability and A1C were reduced with LY2605541 compared with insulin glargine (both P < 0.001). Mealtime insulin dose decreased with LY2605541 and increased with insulin glargine. Mean weight decreased 1.2 kg with LY2605541 and increased 0.7 kg with insulin glargine (P < 0.001). The total hypoglycemia rate was higher for LY2605541 (P = 0.04) and the nocturnal hypoglycemia rate was lower (P = 0.01), compared with insulin glargine. Adverse events (including severe hypoglycemia) were similar, although more gastrointestinal-related events occurred with LY2605541 (15% vs. 4%, P < 0.001). Mean changes (all within normal range) were higher for alanine aminotransferase, aspartate aminotransferase, triglycerides, and LDL-cholesterol and lower for HDL-cholesterol with LY2605541 compared with insulin glargine (all P < 0.02). CONCLUSIONS In type 1 diabetes, compared with insulin glargine, LY2605541, a novel, long-acting basal insulin, demonstrated greater improvements in glycemic control, increased total hypoglycemia, and reduced nocturnal hypoglycemia, as well as reduced weight and lowered mealtime insulin doses.

Trial registration: ClinicalTrials.gov NCT01049412.

Figures

Figure 1
Figure 1
Daily mean (± SE) BG at baseline and at 8 weeks for LY2605541 (LY) and insulin GL. Baseline for both treatments, ▨; insulin GL, □; LY2605541, ■. Inset graph shows mean (± SE) 8-point SMBG profile at baseline and after 8 weeks of treatment for LY2605541 and GL. Baseline for both treatments, △; insulin GL, ○; LY2605541, ■. *Times at which BG was significantly lower (P < 0.01) after 8 weeks of LY2605541 treatment compared with GL.
Figure 2
Figure 2
Mean A1C and weight during treatment with LY2605541 and insulin GL. Patients received treatment with one basal insulin for the first 8-week treatment period and were switched to the other basal insulin for the second treatment period. Insulin GL, ○; LY2605541, ■. A: Mean (± SE) A1C throughout the two treatment periods. B: Mean (± SE) weight throughout the two treatment periods.

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