TY - JOUR

T1 - The effect of insulin analogs in people with type 1 diabetes at increased risk of severe hypoglycemia

AU - Broeng-Mikkelgaard, Sofie

AU - Brøsen, Julie Maria Bøggild

AU - Kristensen, Peter Lommer

AU - Thorsteinsson, Birger

AU - Pedersen-Bjergaard, Ulrik

N1 - Publisher Copyright: Copyright © 2023 Broeng-Mikkelgaard, Brøsen, Kristensen, Thorsteinsson and Pedersen-Bjergaard.

PY - 2023

Y1 - 2023

N2 - Type 1 diabetes is characterized by insulin deficiency, and treatment is to supply insulin mimicking the physiological endogenous insulin secretion. Since its discovery, insulin therapy has evolved, and since the 1990s, an increasing number of insulin analogs with various pharmacokinetic and pharmacodynamic profiles have become available. Despite the improvement of insulin therapy, hypoglycemia remains the main side effect and is a daily concern for many people with diabetes and their families. A proportion of people with type 1 diabetes are at increased risk of hypoglycemia and experience recurring episodes. When designing insulin trials, this group of people is most often excluded in order to reduce the risk of adverse study outcomes, even though it may be the group that may benefit the most from treatment with new insulins. The results of the phase III trials, therefore, underestimate the clinical impact and pharmacoeconomic effect of the implementation of new insulins in the broader type 1 diabetes population. This paper reviews the four insulin trials that include people at increased risk of hypoglycemia. In general, the studies confirm the results from phase III trials in terms of similar reduction and maintenance of HbA1c, as well as relative rate reductions of hypoglycemia. However, the absolute treatment differences in the reduction of hypoglycemia are even greater in the trials, including people at high risk of hypoglycemia. This emphasizes the importance of including people at high risk of hypoglycemia to assess the full clinical and pharmacoeconomic benefit of new insulins.

AB - Type 1 diabetes is characterized by insulin deficiency, and treatment is to supply insulin mimicking the physiological endogenous insulin secretion. Since its discovery, insulin therapy has evolved, and since the 1990s, an increasing number of insulin analogs with various pharmacokinetic and pharmacodynamic profiles have become available. Despite the improvement of insulin therapy, hypoglycemia remains the main side effect and is a daily concern for many people with diabetes and their families. A proportion of people with type 1 diabetes are at increased risk of hypoglycemia and experience recurring episodes. When designing insulin trials, this group of people is most often excluded in order to reduce the risk of adverse study outcomes, even though it may be the group that may benefit the most from treatment with new insulins. The results of the phase III trials, therefore, underestimate the clinical impact and pharmacoeconomic effect of the implementation of new insulins in the broader type 1 diabetes population. This paper reviews the four insulin trials that include people at increased risk of hypoglycemia. In general, the studies confirm the results from phase III trials in terms of similar reduction and maintenance of HbA1c, as well as relative rate reductions of hypoglycemia. However, the absolute treatment differences in the reduction of hypoglycemia are even greater in the trials, including people at high risk of hypoglycemia. This emphasizes the importance of including people at high risk of hypoglycemia to assess the full clinical and pharmacoeconomic benefit of new insulins.

KW - hypoglycemia

KW - insulin analogs

KW - insulin degludec

KW - insulin detemir

KW - insulin glargine

KW - insulin lispro

KW - randomized clinical trials

KW - type 1 diabetes

U2 - 10.3389/fphar.2023.1301931

DO - 10.3389/fphar.2023.1301931

M3 - Review

C2 - 38089060

AN - SCOPUS:85179342114

VL - 14

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 1301931

ER -