Clinical Considerations When Initiating and Titrating Insulin Degludec/Liraglutide (IDegLira) in People with Type 2 Diabetes

Abstract

Therapeutic inertia is a substantial obstacle to the initiation of insulin therapy in people with uncontrolled type 2 diabetes (T2D). This effect has in part been perpetuated by concerns over the impact of a burdensome regimen and the increased risk of hypoglycemia and body weight gain often associated with insulin use. An effective, yet simple, less burdensome regimen with a lower risk of body weight gain and hypoglycemia compared with an insulin-only regimen, may help to address these concerns more effectively. We review the available clinical and real-world data on IDegLira, a once-daily, injectable, fixedratio combination of insulin degludec (degludec) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, in people with T2D. Evidence from the comprehensive DUAL clinical trial program suggests an advantage of IDegLira over traditional insulin therapies in a number of clinical outcomes, including maintenance of glycemic control, achievement of glycemic targets, reducing the risk of hypoglycemia, and body weight loss. These findings were demonstrated in participants with T2D irrespective of prior GLP-1RA and insulin use. Furthermore, the individual components of IDegLira have confirmed safety (degludec) or significant benefit in terms of improvement of cardiovascular risk (liraglutide). As an injectable therapy that is simple to titrate, IDegLira has the potential to optimize the ability to achieve relevant glycemic targets, and offers a suitable treatment option for people with T2D requiring insulin therapy who are at risk of hypoglycemia or weight gain.

Technology in the management of type 2 diabetes: Present status and future prospects

“…As weight gain is a commonly reported reason for avoidance of insulin therapy in T2D, this is an important point to reiterate to clinicians and people who have expressed these concerns. 82 Although many people with T2D have difficulty achieving glucose targets and therefore meet criteria for insulin therapy, a major barrier to treatment intensification is the fear of hypoglycaemia. It is known that severe hypoglycaemia in people with T2D is associated with microvascular and macrovascular adverse events and death.…”

“…The results of the larger VIVID 72 and OpT2mise 73 RCTs, and meta-analysis by Pickup et al 66 were reassuring as no significant difference in weight gain was observed. As weight gain is a commonly reported reason for avoidance of insulin therapy in T2D, this is an important point to reiterate to clinicians and people who have expressed these concerns 78 .…”

Deciphering the Roles of Metformin in Alzheimer’s Disease: A Snapshot

“…Researchers have even proposed the term “Type-3-Diabetes” for AD due to the significant association ( Kandimalla et al, 2017 ), which implies the potential of anti-diabetic medicine to prevent or treat AD. Intranasal insulin has been considered as a promising candidate for AD prevention and treatment due to its safety and current encouraging clinical evidence on its effectiveness ( Harris et al, 2020 ; Hallschmid, 2021 ). As for other anti-diabetic drugs, including dipeptidyl peptidase (DPP)-IV inhibitors and Glucagon-like peptide-1 (GLP-1) analogues, they were found to decrease neuroinflammation, Aβ load and tau phosphorylation in experimental studies, while clinical evidence is still lacking ( McClean et al, 2011 ; Yang et al, 2013 ; Kosaraju et al, 2017 ; Boccardi et al, 2019 ).…”

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines

“…These are composed of two antihyperglycaemic drugs that maintain their distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties despite being administered as a co‐formulation 9 and can allow for a comparatively simple insulin regimen, with fewer injections and greater flexibility in dosing time than basal‐plus/basal–bolus therapy 3 . Available fixed‐ratio co‐formulations include insulin degludec/insulin aspart (IDegAsp), 10 insulin degludec/liraglutide 11 and insulin glargine/lixisenatide 12 …”

“…These are composed of two antihyperglycaemic drugs that maintain their distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties despite being administered as a co-formulation 9 and can allow for a comparatively simple insulin regimen, with fewer injections and greater flexibility in dosing time than basal-plus/basal-bolus therapy. 3 Available fixed-ratio coformulations include insulin degludec/insulin aspart (IDegAsp), 10 insulin degludec/liraglutide 11 and insulin glargine/lixisenatide. 12 IDegAsp is the first fixed-ratio co-formulation of two different insulin analogues, comprising insulin degludec (degludec) (70%), a basal insulin analogue with an ultra-long duration of action, and rapid-acting insulin aspart (IAsp) (30%), 10 thereby providing basal and prandial insulin cover when administered with meals.…”