Efficacy and Safety of Ultra-rapid Lispro Insulin in Managing Type-1 and Type-2 Diabetes: A Systematic Review and Meta-Analysis.

Abstract

Mechanistically, subcutaneous ultra-rapid lispro (URLi) is faster than lispro. Whether this translates into a better post-prandial glucose (PPG) and glycemic control in type-1 diabetes (T1DM) and type-2 diabetes (T2DM) is unclear. Hence, we undertook this meta-analysis. Databases were searched for randomized controlled trials (RCTs) involving patients with T1DM/T2DM receiving URLi in intervention-arm, and placebo/prandial insulin as control. The primary outcome was a change in PPG. Secondary outcomes were alterations in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), time in range (TIR), and adverse events. Data from six RCTs (3687 patients) were analyzed. Lispro was the control arm in all RCTs. T1DM patients receiving mealtime URLi had lower HbA1c [mean difference (MD) -0.07%; 95% confidence interval (CI): -0.12 to - 0.01; P = 0.02; I2 = 42%] and 1-h PPG [MD - 1.18 mmol/L; 95% CI: -1.91 to - 0.44; P = 0.002; I2 = 100%]. T1DM patients receiving post-meal URLi had comparable HbA1c [MD 0.07%; 95% CI: -0.01 to 0.15; P = 0.07; I2 = 55%] and 1-h PPG [MD 0.22 mmol/L; 95% CI: -0.80 to 1.24; P = 0.67; I2 = 100%). T1DM patients on pumps receiving URLi had comparable TIR [MD 1.70; 95% CI: -0.29 to 3.69; P = 0.09; I2 = 98%], lower time in blood glucose <3 mmol/L with increased infusion-set reactions. T2DM patients receiving mealtime URLi had lower 1-h PPG [MD - 0.66 mmol/L; 95% CI: -0.69 to - 0.63; P < 0.00001; I2 = 0%(LH), 2-h-PPG [MD - 0.96 mmol/L; 95% CI: -1.00 to - 0.92; P < 0.00001; I2 = 0%], higher FPG [MD 0.18 mmol/L; 95% CI: 0.11-0.24; P < 0.00001; I2 = 20%], and higher HbA1c [MD 0.07%; 95% CI: -0.06 to 0.08; P < 0.00001; I2 = 0%]. Pre-meal URLi is better than lispro with regard to PPG control. Post-meal URLi is as good as lispro for PPG control. Post-meal URLi is inferior to pre-meal URLi for PPG control.