Superior efficacy of insulin degludec/liraglutide versus insulin glargine U100 as add‐on to sodium‐glucose co‐transporter‐2 inhibitor therapy: A randomized clinical trial in people with uncontrolled type 2 diabetes

Aims To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with its individual components in Japanese people with type 2 diabetes (T2D) uncontrolled on an oral antidiabetic drug (OAD). Materials and methods This 52‐week, open‐label, multicentre, treat‐to‐target trial randomized participants (n = 819) 1:1:1 to IDegLira, liraglutide 1.8 mg or degludec, as add‐on to their pre‐trial OAD. The maximum IDegLira dose was 50 dose steps (50 U degludec/1.8 mg liraglutide), there was no maximum dose for degludec, and both were titrated based on individual blood glucose measurements. Results After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were −6.91 mmol/mol (95% confidence interval [CI] –8.18; −5.64) and −5.30 mmol/mol (95% CI −6.58; −4.03), confirming non‐inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]). Mean body weight changes were 2.9 kg, 4.1 kg and −1.0 kg with IDegLira, degludec and liraglutide, respectively, showing superiority of IDegLira versus degludec (P = .0001), but a significant difference in favour of liraglutide (P < .0001). Rates of severe or blood glucose‐confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001). Mean daily total insulin dose was lower with IDegLira (27.7 U) versus degludec (34.8 U; P < .0001). Overall adverse event (AE) rates were similar. In total, 34.9%, 22.9% and 41.8% of IDegLira‐, degludec‐ and liraglutide‐treated participants experienced gastrointestinal AEs. Conclusion IDegLira was superior to degludec and liraglutide in terms of HbA1c reduction and superior to degludec in terms of body weight change and rates of hypoglycaemia in Japanese people with T2D.

Section: Introductionmentioning

confidence: 78%

Superior efficacy with a fixed‐ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin‐naïve Japanese patients with type 2 diabetes in a phase 3, open‐label, randomized trial

Kaku

Araki

Tanizawa

et al. 2019

“…IDegLira is a fixed‐ratio combination of basal insulin degludec 100 units/mL (degludec) and the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) liraglutide (3.6 mg/mL) that is administered as a simple once‐daily injection . The safety and efficacy of IDegLira were investigated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) clinical trial programme …”

Section: Introductionmentioning

confidence: 99%

“…The DUAL II and DUAL IX trials assessed the safety and efficacy of IDegLira in patients with T2D treated with oral antidiabetic drug (OAD) therapy or basal insulin (DUAL II). The DUAL II trial established the distinct contribution of the liraglutide component of IDegLira by comparing IDegLira with degludec, both capped at 50 U, and the DUAL IX trial investigated IDegLira versus insulin glargine 100 units/mL (IGlar U100) added on to sodium‐glucose co‐transport protein‐2 inhibitors (SGLT2is) . Patients discontinued SUs in DUAL II or dipeptidyl peptidase‐4 inhibitors (DPP4is) in DUAL IX before starting IDegLira.…”

Section: Introductionmentioning

confidence: 99%

Benefits of insulin degludec/liraglutide are maintained even in patients discontinuing sulphonylureas or dipeptidyl peptidase‐4 inhibitors upon initiation of degludec/liraglutide therapy: A post hoc analysis of the DUAL II and DUAL IX trials

Őrsy

Stachlewska

Salvesen-Sykes

et al. 2020

Self Cite

Aim To investigate the efficacy and safety of initiating insulin degludec/liraglutide (IDegLira) in patients with type 2 diabetes (T2D) who had discontinued pretrial sulphonylureas (SUs) or dipeptidyl peptidase‐4 inhibitors (DPP4is) versus patients not previously treated with these regimens. Materials and Methods In DUAL II, patients with T2D uncontrolled on basal insulin and metformin ± SU/glinides were randomized to insulin degludec or IDegLira (both capped at 50 U). In DUAL IX, patients were randomized to insulin glargine U100 (no maximum dose) or IDegLira, as add‐on to sodium‐glucose co‐transporter‐2 inhibitors ± oral antidiabetic drugs. In this post hoc analysis, patients were grouped according to pretrial use of SU (DUAL II) or DPP4i (DUAL IX). Results Regardless of pretrial SU/DPP4i use, IDegLira was favourable versus insulin comparators with respect to change in HbA1c and body weight. Lower hypoglycaemia rates and comparable end‐of‐trial daily insulin dose were achieved with IDegLira, regardless of pretrial regimen. There was no clinically relevant increase in mean self‐measured blood glucose in the early weeks after IDegLira initiation. There was no statistically significant interaction between the randomized treatments and previous SU/DPP4i use. Conclusions IDegLira was more favourable compared with degludec or glargine U100 in terms of change in HbA1c and body weight, regardless of antecedent treatment. Clinicians should be aware of a potential transient rise in self‐measured blood glucose when transitioning therapy in patients. This shows that SUs/DPP4is can be safely discontinued, without deterioration in glycaemic control when initiating IDegLira, allowing a simplified treatment regimen.

“…The availability of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), injectable incretin mimetics that lower fasting and post‐prandial blood glucose in a glucose‐dependent manner, provides patients who have uncontrolled T2D with basal insulin an effective intensification option that offers a lower treatment burden, a reduced risk of hypoglycaemia, and weight loss or weight maintenance as opposed to weight gain, compared with intensifying therapy with prandial insulin . Fixed ratio combination (FRC) injectable therapies with basal insulin/GLP1‐RA therapy provide these advantages and further reduce treatment burden …”

Section: Introductionmentioning

confidence: 99%

“…Results from the DUAL clinical trial programme demonstrated that the FRC IDegLira combines the benefits of the basal insulin degludec (degludec) and the GLP‐1RA, liraglutide, in a single daily injection, with a stepwise titration algorithm that contributes to attenuating the primary side effects associated with each component . The DUAL VII trial compared the efficacy and safety of IDegLira with basal–bolus therapy (insulin glargine 100 units/mL [IGlar U100] + insulin aspart [IAsp] ≤4 times daily) in patients with T2D who were inadequately controlled with basal insulin and metformin .…”

Section: Introductionmentioning

confidence: 99%

IDegLira improves patient‐reported outcomes while using a simple regimen with fewer injections and dose adjustments compared with basal–bolus therapy

Miller¹,

Doshi²,

Grøn

et al. 2019

Self Cite

Aims Basal–bolus therapy is associated with greater treatment burden and lower adherence compared with more simplified regimens. This post hoc analysis studied the difference between insulin degludec/liraglutide (IDegLira) and basal–bolus therapy on number of injections, dose adjustments and patient outcomes in the DUAL VII trial. Materials and methods DUAL VII was a 26‐week, open‐label trial in which patients with uncontrolled type 2 diabetes who were using metformin and insulin glargine 100 units/mL (20–50 U) were randomized 1:1 to IDegLira (N = 252) or basal–bolus (insulin glargine U100 + insulin aspart ≤4 times/day) (N = 254). This post hoc analysis reports the observed mean number of injections and cumulative dose adjustments during 26 weeks of treatment. Patient‐reported outcomes (Treatment‐Related Impact Measure – Diabetes [TRIM‐D] and Short Form‐36 Health Survey version 2 [SF‐36v2]) were collected at scheduled visits and change from baseline scores calculated. Results The clinical benefits (non‐inferior HbA1c reductions, weight benefit, less hypoglycaemia) of IDegLira vs basal–bolus therapy were achieved with fewer cumulative dose adjustments (16.6 vs 217.2, respectively) and fewer injections (1 vs ≥3 per day, respectively). Patients treated with IDegLira experienced significant improvements across all TRIM‐D domains compared with those undergoing basal–bolus therapy. The SF‐36v2 showed improvements in both treatment arms with no significant difference between arms in the physical component summary, but there was a significant improvement in patients treated with IDegLira in the mental component summary (P = .0228). Conclusions These findings, combined with the DUAL VII results, suggest that IDegLira, through a more simplified regimen versus basal–bolus therapy, may help improve patient adherence and improve patient outcomes related to diabetes management, treatment burden and mental health, which in turn may assist in the timely achievement of glycaemic control in clinical practice.