Glucose clamp studies assessing the time–action profile of long-acting insulin analogues have reported conflicting results.
In an attempt to reconcile the data, we organised an expert meeting of four leading European clamp groups, during which consensus
was reached on some but not all points discussed. In this paper, which reflects our personal views only, we aim to provide
guidance for readers and reviewers on the interpretation of this type of clamp study and to clarify its inherent limitations.
Glucose clamp studies are either performed manually or using an automated procedure, but differences in clamp methodology
hardly seem a satisfactory explanation for the conflicting results. (Un)conscious investigator-related bias, especially during
manual studies, cannot be ruled out, despite attempts at blinding the study insulin during the clamp.
The duration of action of study insulins is influenced by many factors, such as glucose and insulin levels prior to injection,
endogenous insulin secretion, insulin dose, definitions used for onset and end of action, and insulin sensitivity (which is
influenced by the necessity of fasting during the clamp). These factors limit the translation of clamp study results into
daily practice.
Because of the inherent limitations of the glucose clamp technique and the lack of reproducibility of the outcomes, its results
should be regarded as no more than an indication of the clinical action profile of long-acting insulin preparations.
Keywords Insulin time–action profiles - Isoglycaemic clamp studies - Long-acting insulin analogues - Pharmacodynamics