Current Status of Weekly Insulin Analogs and Their Pharmacokinetic/Pharmacodynamic Evaluation by the Euglycemic Clamp Technique

Clin Pharmacol Drug Dev. 2023 Sep;12(9):849-855. doi: 10.1002/cpdd.1296. Epub 2023 Jul 13.

Abstract

Diabetes mellitus represents a significant global health threat characterized by hyperglycemia caused by inadequate insulin secretion and/or insulin resistance. Exogenous insulin supplements had been recognized as a crucial treatment for achieving successful glycemic control in patients with Type 1 and most patients with Type 2 diabetes. Over the past century, substantial progress has been made in the development of novel insulin formulations, including the super-fast-acting and long-acting basal insulin analogs, of which the latter is indispensable for the management of nocturnal fasting and intraprandial blood glucose within the normal physiological range. Recently, combining chemical and genetic engineering with drug optimization have resulted in a formidable evolution in ultra-long-acting weekly insulin. Here, the current state of once-weekly insulin analogs and the euglycemic clamp technique used in the early clinical development to elucidate the pharmacokinetics and pharmacodynamics of this type of novel weekly insulin analogs were systematically overviewed.

Keywords: diabetes mellitus; euglycemic clamp; insulin analogs; once-weekly insulin; pharmacokinetics/pharmacodynamics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / pharmacokinetics
  • Insulin
  • Insulin, Long-Acting / pharmacokinetics
  • Insulin, Long-Acting / therapeutic use

Substances

  • Insulin
  • Hypoglycemic Agents
  • Insulin, Long-Acting