Differentiating Basal Insulin Preparations: Understanding How They Work Explains Why They Are Different

Abstract

Since the introduction of insulin as a life-saving agent for patients with type 1 diabetes, insulin preparations have evolved to approximate physiologic insulin delivery profiles to meet prandial and basal insulin needs. While prandial insulins are designed to have quick time-action profiles that minimize postprandial glucose excursions, basal insulins are designed to have a protracted time-action profile to facilitate basal glucose control over 24 h. Given that all insulins have the same mechanism of action at the target tissue level, the differences in time-action profiles are achieved through different mechanisms of protraction, resulting in different behaviors in the subcutaneous space and different rates of absorption into the circulation. Herein, we evaluate the differences in basal insulin preparations based on their differential mechanisms of protraction, and the resulting clinical action profiles. Multiple randomized control trials and real-world evidence studies have demonstrated that the newer second-generation basal insulin analogs, insulin glargine 300 units/mL and insulin degludec 100 or 200 units/mL, provide stable glycemic control with once-daily dosing and are associated with a reduced risk of hypoglycemia compared with previous-generation basal insulin analogs insulin glargine 100 units/mL and insulin detemir. These advantages can lead to decreased healthcare resource utilization and cost. With this collective knowledge, healthcare providers and payers can make educated and well-informed decisions when determining which treatment regimen best meets the needs of each individual patient.Funding: Sanofi US, Inc.

Keywords: Basal insulin; Hypoglycemia; Pharmacodynamics; Pharmacokinetics; Protraction; Second-generation long-acting insulin.

Fig. 1

Advances in insulin development. Gla-100 insulin glargine 100 units/mL, Gla-300 insulin glargine 300 units/mL, IDeg insulin degludec, IDet insulin detemir

Fig. 2

Compact depot formation with Gla-300 results in more gradual insulin release as compared with Gla-100 [1, 27, 48, 49]. Gla-100 insulin glargine 100 units/mL, Gla-300 insulin glargine 300 units/mL, SC subcutaneous

Fig. 3

Mode of protraction of IDeg. IDeg insulin degludec, Zn zinc. Reproduced from Jonassen et al. [50]

Fig. 4

Glucose-lowering effect of different insulin preparations based on data from published PD studies of patients with T2D. Gla-100 insulin glargine 100 units/mL, IDet insulin detemir, NPH neutral protamine Hagedorn, PD pharmacodynamic, T2D type 2 diabetes. Adapted from Evans, 2011 [7] © 2011, Blackwell Publishing Ltd.

Fig. 5

Glucose infusion rate profile of a Gla-300 and b IDeg compared with Gla-100. Gla-100 insulin glargine 100 units/mL, Gla-300 insulin glargine 300 units/mL, IDeg insulin degludec. Reproduced with permission from Becker et al. [27] © 2015, American Diabetes Association

Fig. 6

a Mean glucose infusion rate profile, b mean free serum insulin concentration of Gla-300, and c mean total serum concentration of IDeg-100 in patients with T1D. Gla-300 insulin glargine 300 units/mL, IDeg insulin degludec, LLOQ lower limit of quantification, SD standard deviation. Reproduced from Bailey et al. [10] © 2017, The Authors

Fig. 7

Titration of Gla-300 and IDeg using different algorithms. *Not specified in algorithm; **Dose adjustment > 126 mg/dL not specified in algorithm; Gla-300 insulin glargine 300 units/mL, IDeg insulin degludec. Adapted from Riddle et al. [20]; Bolli et al. [21]; Rosenstock et al. [22]; Yki-Järvinen et al. [23]; Davies et al. [24]; Philis-Tsimikas et al. [25]; Strojek et al. [26]