The investigational long-acting basal insulin LY2605541 is associated with a lower rate of nocturnal hypoglycemia compared with insulin glargine, while also promoting weight loss. LY2605541 consists of insulin lispro modified with a 20-kDa polyethylene glycol moiety. The large hydrodynamic size of LY2605541 slows insulin absorption and reduces its clearance, resulting in a prolonged duration of action. Exposure is unaffected by renal impairment.
Studies comparing LY2605541 with insulin glargine in patients with type 2 diabetes were presented by Richard M. Bergenstal, MD, Executive Director of the International Diabetes Center at Park Nicollet, MN. LY2605541 and insulin glargine had similar effects on lowering hemoglobin (Hb) A1c and average daily self-monitored fasting glucose levels over 12 weeks.
In an open-label study, 289 adults with type 2 diabetes who were receiving neutral protamine Hagedorn or insulin glargine were randomized in a 2:1 ratio to morning administration of LY2605541 or to insulin glargine.
The primary end point was the reduction in fasting plasma glucose (FPG) measured by self-monitoring of blood glucose. In the LY2605541 group, mean FPG at week 12 was 118 mg/dL, and in patients assigned to insulin glargine it was 117 mg/dL, a difference that was not significant. The mean HbA1c level declined from 7.8% to 7.2% with glargine, and from 7.7% to 7.0% with LY2605541, a nonsignificant difference, said Dr Bergenstal.
The mean body weight declined by 0.58 kg from baseline to week 12 in the LY2605541 group and increased by 0.31 kg in the glargine group, a 0.84-kg difference.
Patients assigned to LY2605541 had a 48% reduction in the rate of nocturnal hypoglycemic events compared with glargine (0.25 events vs 0.39 events per patient for 30 days).
LY2605541 was associated with mean increases in levels of alanine aminotransferase and aspartate aminotransferase of 9 U/L and 4 U/L, respectively, compared with insulin glargine, but these levels remained within the normal range.
A substudy assessed hypoglycemia and glucose variability using continuous glucose monitoring of interstitial glucose in 76 of the 289 patients.
At 12 weeks, patients treated with LY2605541 spent less time with interstitial glucose <70 mg/dL than glargine-treated patients during the nocturnal period (11 minutes vs 38 minutes, respectively) and during the 24-hour period. Fewer LY2605541-treated patients experienced hypoglycemia (50.0% vs 78.3%, respectively), including nocturnal hypoglycemia (20.5% vs 47.8%, respectively).
The 2 treatments resulted in similar mean glucose values during a 24-hour period at 12 weeks.