ReviewA Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus
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.
References (45)
- et al.
Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial
Lancet
(2012) - et al.
Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial
Lancet
(2011) - et al.
Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial
Lancet
(2012) - et al.
Efficacy and safety of insulin degludec three times a week versus insulin glargine once a day in insulin-naive patients with type 2 diabetes: results of two phase 3, 26 week, randomised, open-label, treat-to-target, non-inferiority trials
Lancet Diabetes Endocrinol
(2013) - et al.
Design of DEVOTE (Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events)—DEVOTE 1
Am Heart J
(2016) - et al.
Insulin glargine: a systematic review of a long-acting insulin analogue
Clin Ther
(2003) - International Diabetes Federation (IDF). IDF Diabetes Atlas Sixth Edition Poster Update 2014....
- et al.
Basal insulin analogues in the management of diabetes mellitus: What progress have we made?
Diabetes Metab Res Rev
(2014) - et al.
Twice-daily compared with once-daily insulin glargine in people with type 1 diabetes using meal-time insulin aspart
Diabet Med
(2006) - et al.
Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population-based study
Diabet Med
(2005)
Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes
Diabetes
Observational, open-label study of type 1 and type 2 diabetes patients switching from human insulin to insulin analogue basal-bolus regimens: insights from the PREDICTIVE study
Curr Med Res Opin
Trends in prevalence and control of diabetes in the United States, 1988-1994 and 1999-2010
Ann Intern Med
The development of new basal insulins: is there any clinical advantage with their use in type 2 diabetes?
Expert Opin Biol Ther
Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes
Diabetes Obes Metab
Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin
Pharm Res
Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes
Diabetes Obes Metab
Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine
Diabetes Care
Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN((R)) Basal-Bolus Type 1): 2-year results of a randomized clinical trial
Diabet Med
Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension
J Clin Endocrinol Metab
Treating to target in type 2 diabetes: the BEGIN trial programme
J Assoc Physicians India
Cited by (17)
Insulin glargine Gla-300 (Toujeo®): From formulation to clinical practice
2019, Medecine des Maladies MetaboliquesEfficacy and safety of the second generation basal insulin analogs in type 2 diabetes mellitus: A critical appraisal
2019, Diabetes and Metabolic Syndrome: Clinical Research and ReviewsCitation Excerpt :The total number of all AEs was similar for patients receiving IDeg vs. Glar-100 and Glar-300 vs. Glar-100. The most common AEs were headache, upper respiratory infections, and pharyngitis, and they were similar between the treatment groups [45,46] (Table 1). The average 24h SMPG reduction from BL to study end was significantly better for Glar-100 only for BEGIN Basal-Bolus Type 2 (in the BEGIN trials); in the EDITION trials there were no significant differences in this parameter (Fig. 1).
Efficacy and safety of the second generation basal insulin analogs in type 2 diabetes mellitus: A critical appraisal
2019, Diabetes and Metabolic Syndrome: Clinical Research and ReviewsCitation Excerpt :Moreover, there were no significant differences in the pre-breakfast SMPG with IDeg and Glar-100 (for BEGIN trials). While in EDITION 1 and 3, reduction in pre-breakfast SMPG was significantly better for Glar-100 vs. Glar-300 [44–50]. No significant weight differences were observed In the BEGIN trials; in the BEGIN Flex, the difference in weight between IDeg and Glar-100 was 0.3 kg, but statistical significance was not reported.
Diagnosis and insulin therapy of type 1 diabetes mellitus (Update 2023)
2023, Wiener Klinische WochenschriftEffects of Ultra-Long-Acting Insulin Compared to Long-Acting Insulin on Diabetic Ketoacidosis Incidence in Type 1 Diabetes Mellitus Patients
2022, Diabetes, Metabolic Syndrome and Obesity