Can a fixed-ratio combination of insulin degludec and liraglutide help Type 2 diabetes patients to optimize glycemic control across the day?

Abstract

‘IDegLira’ combines insulin degludec (IDeg) with the glucagon-like peptide-1 analog liraglutide (Lira) at a ratio of 1 unit IDeg to 0.036 mg Lira. The two components have complementary therapeutic actions for the treatment of Type 2 diabetes. Studies have shown that combinations of basal insulin with glucagon-like peptide-1 receptor agonists can be clinically successful, lowering elevated blood glucose with a low risk of hypoglycemia and weight gain. IDegLira is being assessed in a series of studies (two already published), which provide insights into its clinical utility in previously insulin-naive patients and those failing to achieve good glycemic control on a basal-only insulin regimen. This article critically examines the available data to assess the product’s likely clinical profile.

Keywords:

• basal insulin
• combination therapy
• DUAL study
• incretin therapy
• insulin degludec
• liraglutide
• Type 2 diabetes

Financial & competing interests disclosures

For Novo Nordisk R Simpson has been/or is a member of a number of advisory boards, PI for a range of clinical trials, including the DUAL program, and has received funding for investigator-initiated trials. Has also received funding for investigator-initiated research from Merck and AstraZeneca, and conducted industry-sponsored trials for Sanofi, Eli Lilly, GlaxoSmithKline, Takeda, Janssen, Pfizer, Merck, Bristol-Myers Squibb, AstraZeneca and ResMed. Also speaker for AstraZeneca, GlaxoSmithKline, Sanofi and Eli Lilly. A King has acted as a speaker for Sanofi, Lilly, Novo Nordisk, Medtronic, Animas, Takeda, Janssen, Lifescan, Pfizer, GlaxoSmithKline and Amylin. Consultant for Sanofi, Lilly, Novo Nordisk, Medtronic, Animas, Takeda, Janssen and Lifescan. Received research funding from Sanofi, Lilly, Novo Nordisk, Medtronic, Animas, Takeda and Amylin. Participated in the organization of, reviewing and rewriting of this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Murray Edmunds from Watermeadow Medical, UK, for help in the drafting of this manuscript. This assistance was funded by Novo Nordisk.

Key issues

• Effective control of hyperglycemia is recommended for patients with Type 2 diabetes (T2D) to optimize prognosis, but patients struggle to meet their blood glucose targets due to the side effects and complexity of treatment, especially with intensified insulin therapy.

• A potential alternative to a treatment regimen that combines basal and bolus insulin injections is a regimen that combines basal insulin with glucagon-like peptide-1 receptor agonists (GLP-1RAs).

• GLP-1RAs have pharmacological actions that complement those of basal insulin; they stimulate insulin and inhibit glucagon secretion glucose-dependently as well as reducing appetite, whereas a basal insulin continuously supplements the requirement for endogenous insulin secretion.

• The expected benefits of this regimen are dynamic control of both postprandial and fasting blood glucose, with a reduced exogenous insulin dose requirement, a low risk of hypoglycemia and minimal weight gain.

• Studies of regimens combining these agents as separate injections have borne out these expectations.

• IDegLira is a fixed combination of the basal insulin, insulin degludec, and the GLP-1RA, liraglutide, which enables such a regimen to be given as a single daily injection.

• Two studies (one in previously insulin-naive T2D patients, and one in T2D patients not well controlled on basal insulin) have demonstrated the clinical utility of IDegLira as well as the pharmacological synergy of the two components.

• IDegLira is a potentially valuable addition to the T2D therapeutic armamentarium. The fixed-dose ratio presents some clinical challenges, however, but further studies (some already underway) will help determine its optimal role and how best to exploit its potential in clinical practice.