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Glucose clamp studies form an integral part of the early development of insulin therapies. Data generated in these studies are used to establish pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the agents, but methodological differences confound comparison of results from different glucose clamp studies. The first part of this series on glucose clamp studies discussed practical tips for the interpretation of glucose clamp studies. The second part of the series compares the PK/PD profiles of longer-acting basal analogue insulins, insulin degludec (IDeg) and insulin glargine U300 (Gla-300). The patient populations for glucose clamp studies with these analogue insulins differ, and therefore direct comparison of the data is not always possible. The maximum duration of action of IDeg is reported as 42 h and that of Gla-300 as 36 h, translating to 24 h coverage. The plasma insulin concentration of IDeg is 56 times that of Gla-300. Results from phase III clinical trials for these analogue insulins confirm the predictability and low within-subject variability observed in glucose clamp studies. Insight into the PK/PD profiles of longer-acting basal analogue insulins allows the treating physician to utilise these characteristics to optimise the treatment of their patients with diabetes. [ABSTRACT FROM AUTHOR]

Glucose clamp studies are used to determine pharmacokinetics (PK) and pharmacodynamics (PD) of analogue insulins. With the development of longer-acting basal analogue insulins, including glargine 300 (Gla-300) and insulin degludec (IDeg), results from numerous glucose clamp studies are readily available. However, interpreting PK/PD profiles in a scientifically sound manner can be a challenging feat. This is the first in a series of publications that will suggest practical tips for interpreting and comparing results from glucose clamp studies. Variations in the glucose clamp methodology, duration of clamp studies and glucose clamp targets influence the study design and results significantly. Selection of study populations, including healthy patients or patients with Type 1 or 2 diabetes mellitus, has important implications. The dose of study insulin should reflect that of the general treatment population, and ideally steady-state conditions should be used. During the study the plasma insulin concentration and glucose infusion rate describe the pharmacokinetics and pharmacodynamics of the study insulin. With these practical tips in mind, results of glucose clamp studies can be interpreted in a scientifically correct manner. The next article in this series will discuss the interpretation of PK/PD profiles using two newly developed longer-acting basal analogue insulins: Gla-300 and IDeg. [ABSTRACT FROM AUTHOR]

Purpose/Aim: Negative feedback controls in endocrine regulatory systems are well recognized. The incretins and their role in glucose regulation have been of major interest recently. Whether the same negative control system applies to the regulation of incretin secretion is not clear. We sought to examine the hypothesis that exogenous administration of glucagon like peptide-1, GLP-1(7–36) amide or its metabolite GLP-1(9–36) amide, reduces the endogenous basal release of this incretin.Materials and Methods: We evaluated the endogenous basal release of GLP-1 using two separate study designs. In protocol A we examined the GLP-1(7–36) amide levels during the infusion of GLP-1(9–36) amide. In protocol B, we used PYY and GLP-2 as biomarkers for the endogenous basal release of GLP-1(7–36) amide and assessed the endogenous basal release of these two hormones during the GLP-1(7–36) infusion. Twelve lean and 12 obese subjects were enrolled in protocol A and 10 obese volunteers in protocol B.Results: The plasma levels of GLP-1(7–36) amide in protocol A and PYY and GLP-2 in protocol B remained unchanged during the exogenous infusion of GLP-1(9–36) and GLP-1(7–36) amide, respectively.Conclusions: The negative feedback control system as described by inhibition of the release of endogenous hormone while infusing it exogenously was not observed for the basal secretion of GLP-1(7–36) amide. [ABSTRACT FROM PUBLISHER]