Sultan Linjawi

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, fixed-ratio 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.

This 32-week, open-label, randomized, parallel-group, multinational trial aimed to compare the efficacy and safety of stepwise insulin intensification of biphasic insulin aspart 30 (BIAsp 30) relative to stepwise intensification of a basal–bolus regimen in insulin-naïve adults with type 2 diabetes (T2D) who continued pretrial treatment with metformin and sulfonylurea.

Introduction The progressive nature of type 2 diabetes necessitates treatment intensification. This often involves intensification with oral antidiabetic drugs (OADs) initially, followed by other agents, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), with the majority of patients eventually requiring insulin therapy. Therefore, this trial aimed to investigate the efficacy of IDegLira (combination of insulin degludec and liraglutide) in controlling glycemia in adults with type 2 diabetes who were inadequately controlled on a GLP-1RA and OADs. Methods In this 26-week open-label phase 3b trial, patients on maximum-dose GLP-1RA therapy (liraglutide once daily or exenatide twice daily) with metformin alone or with pioglitazone and/or sulfonylurea were randomized 2:1 to IDegLira once daily (n = 292) or to unchanged GLP-1RA therapy (n = 146), continuing OADs at the pre-trial dose. Results After 26 weeks, HbA_1c reductions were superior with IDegLira versus unchanged GLP-1RA; estimated treatment difference −0.94% (−10.3 mmol/mol), p < 0.001. Mean HbA_1c reduced from 7.8% to 6.4% (61.5 to 46.9 mmol/mol) with IDegLira and from 7.7 to 7.4% (60.8 to 57.1 mmol/mol) with unchanged GLP-1RA. With IDegLira, 75% and 63% of patients achieved HbA_1c <7% and ≤6.5%, compared with 36% and 23% on unchanged GLP-1RA, respectively. Fasting plasma glucose and 9-point self-monitored blood glucose profiles improved significantly more with IDegLira versus unchanged GLP-1RA. The mean change in weight was +2.0 kg with IDegLira, versus −0.8 kg with unchanged GLP-1RA. Rates of confirmed hypoglycemia were low, but higher with IDegLira versus unchanged GLP-1RA. The safety profile of IDegLira was consistent with previous findings; both treatments were well tolerated and the rate of nausea was low in both groups. IDegLira improved patient-reported outcomes versus unchanged GLP-1RA. Conclusions IDegLira provided superior glycemic control versus unchanged GLP-1RA and represents an efficacious intensification approach in patients inadequately controlled on GLP-1RAs. Trial registration ClinicalTrials.gov #NCT01676116. Funding Novo Nordisk.

Objective: IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes. Methods: In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed. Results: At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC_0-4h) than insulin degludec (estimated treatment difference [ETD] −12.79 mg/dl [95% CI: −21.08; −4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD −1.62 mg/dl [95% CI: −10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC_0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD −6.13 mg/dl [95% CI: −10.27, −1.98], P = .0047) and similar reductions versus liraglutide (ETD −1.80 mg/dl [95% CI: −2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec ( P = .048 and P = .006, respectively) and similar to liraglutide ( P = .45 and P = .895, respectively). Conclusions: Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination.