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

Background: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. Methods: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. Results: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%]. Conclusion: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.