M. J. Davies, D. Russell‐Jones, J.‐L. Selam, T. S. Bailey, Z. Kerényi, J. Luo, J. Bue‐Valleskey, T. Iványi, M. L. Hartman, J. G. Jacobson, S. J. Jacober, for the IMAGINE 2 Study Investigators

Basal insulin peglispro is a long-acting insulin analog with hepato-preferential action. This double-blind, randomized, multi-national study compared 52- or 78-week treatment with basal insulin peglispro or insulin glargine, added to pre-study oral antihyperglycemic medications, in insulin-naïve adults with type 2 diabetes. Primary outcome was noninferiority of peglispro to glargine in HbA1c reduction (margin=0.4%). Six gated secondary objectives with statistical multiplicity adjustments assessed other measures of glycemic control. Liver fat content was measured by MRI, in a subset of patients. Peglispro was noninferior to glargine in HbA1c reduction (least-squares mean difference: -0.29% [95%CI: -0.40, -0.19]), and had a lower nocturnal hypoglycemia rate (relative rate [RR]: 0.74 [0.60, 0.91]; p=0.005), more patients achieving HbA1c<7.0% without nocturnal hypoglycemia (odds ratio [OR]: 2.15 [1.60, 2.89], p<0.001), greater HbA1c reduction (p<0.001), and more patients achieving HbA1c<7.0% (OR: 1.97 [95%CI: 1.57, 2.47], p<0.001). Total hypoglycemia rate and fasting serum glucose did not achieve statistical superiority. At 52 weeks, peglispro-treated patients had higher triglycerides (169 vs 151 mg/dL), ALT (34 vs 27 IU/L), and AST (27 vs 24 IU/L). Least-squares mean liver fat content was unchanged with BIL at 52 weeks but decreased 3.1% with glargine (difference: 2.6% [0.9, 4.2]; p=0.002). More peglispro-treated patients experienced adverse injection site reactions (3.5% vs 0.6%, p<0.001). Compared to glargine at 52 weeks, peglispro showed statistically superior reduction in HbA1c, more patients achieving HbA1c targets, less nocturnal hypoglycemia, no improvement in total hypoglycemia, higher triglycerides, higher aminotransferases, and more injection site reactions.