Explorative Study of Pharmacokinetics and Pharmacodynamics after Change in Basal Insulin Infusion Rate

Asymmetric changes in circulating insulin levels after an increase compared with a reduction in insulin pump basal rate in people with Type 1 diabetes

“…Although bolus pharmacokinetics are often used to inform insulin pump basal profiles in clinical practice, our findings show bolus data have limited applicability to routine clinical pump adjustments. Effects of rapidacting insulin analogue subcutaneous basal delivery changes ≥50% have been reported [12][13][14][15]; however, such rate changes are larger than those typically programmed within basal profiles in routine clinical care. After large basal rate increases, times to steady-state insulin have been reported of between 2.5 and 8 h, with larger increments taking longer to reach steady state [12,13,21].…”

“…Effects of rapidacting insulin analogue subcutaneous basal delivery changes ≥50% have been reported [12][13][14][15]; however, such rate changes are larger than those typically programmed within basal profiles in routine clinical care. After large basal rate increases, times to steady-state insulin have been reported of between 2.5 and 8 h, with larger increments taking longer to reach steady state [12,13,21]. The present finding of a 197min delay until 90% steady-state insulin after a 0.2-unit/h rate increase is longer than the report of~2 h after the 0.5unit/h increase, and shorter than 4-8-h reported postincreases of 0.8-1.0 units/h [12,13].…”

“…After large basal rate increases, times to steady-state insulin have been reported of between 2.5 and 8 h, with larger increments taking longer to reach steady state [12,13,21]. The present finding of a 197min delay until 90% steady-state insulin after a 0.2-unit/h rate increase is longer than the report of~2 h after the 0.5unit/h increase, and shorter than 4-8-h reported postincreases of 0.8-1.0 units/h [12,13]. To our knowledge, there are no published studies demonstrating time to steadystate insulin after small clinically relevant basal rate reductions.…”

“…Detailed pharmacokinetic information is available regarding subcutaneous bolus delivery of rapid‐acting insulin analogues ; however, scientific evidence for insulin pump basal rate changes is limited, predominantly pertaining to changes ≥50% . Yet, basal rate changes in clinical care are typically substantially less than 50%.…”

“…Limited evidence regarding increases in basal insulin delivery indicates that, after large increases (e.g. 100%), it takes longer until changes in circulating insulin are observed than after bolus insulin delivery, and time to steady‐state increases with the magnitude of basal increase . In addition, although circadian changes in insulin sensitivity probably influence the impact of insulin on glycaemia, there is a lack of published information about this to guide clinical basal insulin dosing adjustment.…”