Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycemic control in T1D and T2D
Objectives: The basal insulin analog LY2605541 (LY) is a PEGylated insulin lispro with a large hydrodynamic size which delays insulin absorption and reduces clearance, resulting in prolonged duration of action. Improved glycemic control with insulin generally results in weight gain. The present studies investigated how once-daily LY that showed glycemic control comparable with or superior to insulin glargine (GL), relates to weight gain in patients with type 1 or type 2 diabetes.
Methods: Data on body weight were investigated from two studies with LY versus GL. In the first open label, randomized, parallel study, T2D patients (n = 288) received LY or GL over 12 weeks. In the second randomized, open-label, 2 × 2 crossover study patients with T1D received LY or GL (N = 137) over 8 weeks.
Results: Subjects with T2D lost 0.6 kg with LY and gained 0.3 kg with GL (resulting in a treatment difference of -0.84 kg, p < 0.01). Weight loss was more common with LY than GL (57% v 40%, p =.01) and loss of ≥5% body weight was more frequent with LY than GL (5% vs. 0%; respectively, p =.03) with no correlation between baseline BMI and mean weight change. Higher insulin doses correlated with less weight loss with LY (p < 0.01) and greater weight gain with GL (p < 0.01). There was no correlation between hypoglycemia rate and weight change with LY (p =.28).
Subjects with T1D lost 1.2 kg with LY and gained 0.7 kg with GL (resulting in a treatment difference of -1.9 kg, p < 0.01). Weight loss was more common during LY treatment (66% v 40%, p < 0.01) as was loss of ≥5% body weight (12% vs. 1%; p < 0.01) with no correlation between weight and baseline BMI or dose for either insulin. Prandial insulin dose decreased (0.23 U/kg/d to 0.19 U/kg/d) with LY and increased to 0.24 U/kg/d with GL (between-treatment p < 0.01). More mild gastrointestinal (GI) adverse events were reported with LY, but LY-treated subjects with GI events had less weight loss (0.84 kg) than those without (1.33 kg). There was no correlation between hypoglycemia rate and weight change with LY (p =.65).
Conclusions: Improved glycemic control with long acting basal insulin analog LY is associated with weight loss that is not dependent on baseline BMI or rate of hypoglycemic events.
Reference of the Encore Abstract:
* Jacober SJ, Rosenstock J, Bergenstal RM, Prince MJ, Qu Y, Beals JM. Contrasting Weight Changes With LY2605541, a Novel Long-Acting Insulin, and Insulin Glargine Despite Similar Improved Glycemic Control in T1D and T2D [abstract]. Diabetes. 2012;61(Suppl 1):A262 [1023-P].