Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies

While the advantages of the two basal insulin analogues, glargine and detemir, over neutral protamine Hagedorn are well established, the relative merit of the two compared with each other has been a matter of some controversy. The two analogues are popularly perceived to differ from each other in their pharmacodynamic (PD) profiles, in particular with regard to 'flatness' and duration of action. The aim of this review, therefore, is to give a complete overview on the available PD data of both analogues as derived with the glucose clamp technique. In order to improve parity across studies, a common definition for duration of action (time from injection to plasma glucose > 8.3 mmol/l) was applied and study data were recalculated when necessary. Despite differences in methodological details, the results of most clamp studies were very consistent. Glargine and detemir both typically show a gentle rise and fall in glucose-lowering action over time. Duration of action with both analogues is dose dependent, but in the clinically relevant range of 0.35-0.8 U/kg it is close to 24 h in people with type 1 diabetes and in excess of this in people with type 2 diabetes. While both analogues seem to be very similar with regard to the mean shape of their PD profile and duration of action, detemir shows less within-subject variability in its metabolic effect. These findings in experimental glucose clamp studies are consistent with observations in clinical trials and support routine once daily use with either analogue, in particular in people with type 2 diabetes.