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

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.

Ultra-stable insulin-glucagon fusion protein exploits an endogenous hepatic switch to mitigate hypoglycemic risk

“…The former embodiment was herein modeled via continuous IV infusion. Although appropriate for basal-bolus therapy of patients with T1D (with the prandial component provided by a current rapid-acting formulation), it is likely that this biotechnology would also find translational application in basal-only treatment of patients with Type 2 DM (T2D), especially in a once-a-week form (for review, see (57)). The molecular simplicity of a bihormonal FP and its ultra-stability also promise real-world cost advantages (in manufacture, delivery and storage) relative to more complex glucose-responsive technologies (Fig.…”

Efficacy and safety of once-weekly insulin icodec compared to once-daily insulin g U-100 in patients with type II diabetes: a systematic review and meta-analysis

“…In the past century, notable progress has been made in developing innovative Insulin formulations, including highly fast-acting and prolonged-release basal Insulin analogs. The latter is particularly vital for managing overnight fasting and keeping blood glucose levels within the normal physiological range during meals [ 21 ]. As mentioned by Bajaj et al [ 22 ] basal Insulin is typically recommended for T2D when non-Insulin therapies prove insufficient to reach glycemic targets.…”