Review
A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus

https://doi.org/10.1016/j.clinthera.2017.01.007Get rights and content

Abstract

Purpose

The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300).

Methods

A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM.

Findings

The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated.

Implications

The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile.

Introduction

Diabetes represents a significant proportion of the global burden of disease. There are currently 387 million people affected worldwide, and this number is expected to rise to 592 million by 2035.1 One of the mainstays of treatment for diabetes has been insulin, first discovered >90 years ago. Since then, there have been major advances in the production, purification, formulation, and mode of delivery of insulin that have led to the development of basal insulin analogues; these drugs have characteristics that offer additional benefits over older insulin products.2 Despite these improvements, currently available insulin analogues do not deliver steady, peakless, continuous insulin for at least 24 hours in many individuals, and these agents can be associated with adverse events (AEs) such as severe hypoglycemia and nocturnal hypoglycemia.3, 4, 5, 6 In addition, many individuals with diabetes do not achieve optimal glycemic control. According to the latest National Health and Nutrition Examination Survey estimates, glycemic control is not achieved by ~45% of patients currently taking medications for diabetes.7

There is a need for new basal insulin analogues that more closely mimic the action of endogenous insulin and offer a flatter glucose-lowering profile, a longer duration of action, decreased variability in absorption and glucose-lowering action, an ability to be co-formulated with rapid-acting insulin analogues, and a reduced risk of hypoglycemia.8 Several new, long-acting basal insulins are currently under investigation for the treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), including insulin degludec and insulin glargine 300 U/mL (Gla-300). The aim of the present review was to discuss the key clinical trials assessing the efficacy and safety of these 2 long-acting insulins in patients with T1DM and T2DM.

Section snippets

Materials and Methods

The articles included in this review were selected after a search of the published English-language medical literature. A secondary search was performed via review of the references identified in the initial search. The search was conducted from 1966 to 2015 by using PubMed and Google Scholar, using the search terms “insulin degludec” and “insulin glargine” and searching for randomized controlled trials.

A total of 14 studies were identified for insulin degludec (Tables I and II): 3 studies in

Insulin Degludec

Insulin degludec is a new-generation, ultra-long-acting basal insulin. Its name reflects the 3 chemical features of this modified insulin: “de” refers to the deletion of ThrB30, “glu” refers to the side-chain addition of glutamic acid residue, and “dec” refers to a dicarboxylic acid linked to the α-amino group of the attached glutamic acid residue.9 Although native human insulin naturally dimerizes, and then further associates into hexamers in the presence of zinc, insulin degludec

The Role of insulin degludec and gla-300 in therapy

The new long-acting insulin analogues insulin degludec and Gla-300 are promising therapies for the treatment of T1DM and T2DM. They offer longer and flatter pharmacokinetic profiles than the currently used basal insulin analogues, as well as glycemic control with less hypoglycemia. Insulin degludec has been studied more than Gla-300. Its most attractive feature is its extremely long half-life, which allows for dosing intervals of up to 40 hours. This improved flexibility in time-of-day dosing

Conflicts of Interest

The author declares that he has been on advisory boards for and/or received honoraria for educational activities and/or research grants from AstraZeneca, Merck, Janssen, Novo Nordisk, Lilly, Boehringer Ingelheim, Sanofi, and Abbott. The author has indicated that he has no other conflicts of interest regarding the content of this article.

Acknowledgments

Editorial support was provided by Elsevier Canada.

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