Date: 2016-09-16
Type of information: Presentation of results at a congress
phase: 3b
Announcement: presentation of results at the 52nd Annual Meeting of the European Association for the Study of Diabetes (EASD)
Company: Novo Nordisk (Denmark)
Product: Xultophy®/IDegLira (combination of insulin degludec (Tresiba®) and liraglutide (Victoza®))
Action
mechanism: insulin analog/glucagon-like Peptide 1 (GLP-1) analogue. Insulin degludec (Tresiba®) is a once-daily new-generation basal insulin analogue, with an ultra-long duration of action. Liraglutide (Victoza®) is a once-daily human GLP-1 analogue. Insulin degludec binds specifically to the human insulin receptor and results in the same pharmacological effects as human insulin. Liraglutide acts via enhancing glucose-dependent insulin secretion and reducing glucagon release.
Disease: type 2 diabetes
Therapeutic area: Metabolic diseases
Country: Argentina, Australia, Greece, Hungary, Mexico, Russian Federation, Slovakia, South Africa, Spain, USA
Trial
details: DUAL™ V was a phase 3b, 26-week, treat-to-target, randomised, open-label, multicentre trial conducted in 10 countries with 557 patients. The trial was designed to show noninferiority in HbA1c and to subsequently demonstrate superiority in HbA1c, body weight and hypoglycaemia. The trial compared the efficacy and safety of Xultophy® versus insulin glargine, both added on to metformin, in adults with type 2 diabetes uncontrolled on insulin glargine (20–50 units). The pre-trial mean dose of insulin glargine was 32 units. Patients could be titrated to the maximum dose of Xultophy® (equivalent to 50 units of insulin degludec and 1.8 mg of liraglutide) and there was no maximum daily dose of insulin glargine. This trial compares the efficacy and safety of insulin degludec/liraglutide versus insulin glargine in subjects with type 2 diabetes mellitus (DUAL™ V - Basal Insulin Switch).(NCT01952145) DUAL VI was a 32-week, open-label, non-inferiority trial to investigate the safety and efficacy of Xultophy® in insulin-naïve adults with type 2 diabetes uncontrolled on metformin ± pioglitazone. In the trial, 420 participants were randomised 1:1 to receive Xultophy®, titrated either once weekly based on the mean of two pre-breakfast plasma glucose (PG) readings (n=210) or twice weekly based on the mean of three pre-breakfast PG readings (i.e. six readings/week, as for DUAL I-V trials; n=210). (NCT02298192)
Latest
news: * On September 13, 2016, Novo Nordisk presented data showing the odds of reaching fasting plasma glucose (FPG) targets without hypoglycaemia and weight gain were significantly greater for Xultophy® (IDegLira) compared to up-titration with insulin glargine U100 in adults with type 2 diabetes uncontrolled on insulin glargine U100 (20-50 units). Xultophy® is the first once-daily combination of a long-acting insulin (insulin degludec) and a glucagon-like peptide-1 (GLP-1) receptor agonist (liraglutide) in Europe. Results were presented at the 52nd Annual Meeting of the European Association for the Study of Diabetes (EASD) 2016. The post-hoc analysis of the DUAL V phase 3b trial was evaluated using a FPG target of 7.2 mmol/L, selected to better reflect targets used in clinical practice. Data showed that adults treated with Xultophy® were 4.55 times more likely to reach FPG targets without confirmed hypoglycaemia and weight gain vs up-titration with insulin glargine U100 (41.4% vs 14.3%, p<0.0001). The data also demonstrated that significantly more adults achieved HbA1c target of <7% with no hypoglycaemia and no weight gain across baseline HbA1c groups (?7.5, >7.5– * On June 7, 2015, Novo Nordisk announced new phase 3b findings showed adults with type 2 diabetes treated with Xultophy® (IDegLira), a once-daily, single-injection combination of insulin degludec and liraglutide, demonstrated statistically significant reduction in HbA1c (average blood glucose over the previous three months), change in body weight and a lower rate of hypoglycaemia compared with patients treated with insulin glargine. Findings from the phase 3b DUAL™ V 26-week trial that compared the efficacy and safety of Xultophy® versus insulin glargine, both added on to metformin, in patients with type 2 diabetes uncontrolled on insulin glargine (20–50 units/day), were presented at the 75th Annual Scientific Sessions of the American Diabetes Association (ADA) in Boston, Massachusetts, United States. At 26 weeks, patients randomised to Xultophy® treatment achieved a statistically significant mean reduction in HbA1c of 1.8% from baseline (8.4% to 6.6%) compared with a 1.1% reduction (8.2% to 7.1%) achieved by patients who further increased their dose of insulin glargine (p<0.001). In the Xultophy® group, 72% of patients achieved an HbA1c of <7% at the end of the trial, compared with 47% of patients in the insulin glargine group (p?0.001). Furthermore, 39% of patients treated with Xultophy® achieved an HbA1c <7% without hypoglycaemia and weight gain versus 12% treated with insulin glargine (p<0.001).
?8.5 and >8.5%) with Xultophy® vs up-titration with insulin glargine U100 (51% vs 25%; 39% vs 11%; 32% vs 5%; p<0.005 for all).
In addition, FPG and HbA1c were already significantly reduced at weeks 4, 8 and 12 in adults switching to Xultophy® vs up-titration with insulin glargine U100, demonstrating better glycaemic control shortly after transferring to Xultophy® compared to insulin glargine U100.
Also presented at EASD, Novo Nordisk announced results from DUAL VI demonstrating that using a simpler titration algorithm of once-weekly dose adjustments compared to the twice-weekly adjustments used in previous DUAL trials, results in a non-inferior safety and glycaemic efficacy profile for Xultophy® in insulin-naïve adults with type 2
diabetes.
* On September 15, 2015, Novo Nordisk announced that new findings from the DUAL™ V phase 3b clinical trial showed greater improvements in treatment-related satisfaction and patient reported physical health in people treated with Xultophy® versus insulin glargine U100. The DUAL™ V trial evaluated the efficacy and safety of Xultophy® (IDegLira), compared to further intensification with insulin glargine U100 in adults with type 2 diabetes uncontrolled on insulin glargine U100. The findings based on validated patient reported outcomes (PRO) questionnaires
completed by participants in the DUAL™ V trial were announced at the 51st European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.
PRO data provide patients’ perspective on quality of life (QoL) and treatment satisfaction. This type of data is valuable because it reflects patients’ thoughts, complaints and opinions that researchers couldn't otherwise measure or observe.2 PRO from the DUAL™ V trial were assessed by two questionnaires, the Treatment Related Impact Measure for Diabetes (TRIM-D) and Short Form-36 Health Survey (SF-36). The collected data are scored in categories known as domains. The TRIM-D generates a total score based on the assessment of five domains: treatment burden, daily life, diabetes management, compliance and psychological health. Patients treated with Xultophy® achieved a significantly greater improvement from baseline in TRIM-D total score than patients treated with insulin glargine U100 (p=0.003). In particular, patients treated with Xultophy® experienced significantly greater improvement
in the TRIM-D domains, treatment burden (p=0.017) and diabetes management (p<0.001) than patients treated with insulin glargine U100.
SF-36 is a validated generic questionnaire that can be scored into eight domains and two overall component summary scales: the physical component summary (PCS) which is a measure of physical health, and the mental component summary (MCS), which is a measure of emotional health.
Patients treated with Xultophy® experienced a significantly greater improvement in the PCS (p<0.001) score than patients treated with insulin glargine U100, whilst there was no difference with regards to the MCS score between the
two arms.
In addition, findings from the DUAL™ V clinical trial demonstrated that people with type 2 diabetes treated with Xultophy® versus insulin glargine U100 achieved superior HbA1c reductions (1.8% vs 1.1%; p<0.001), body weight change (1.4 kg decrease vs 1.8 kg increase, a 3.2 kg difference; p<0.001) and a 57% lower rate of confirmed
hypoglycaemia (2.2 vs 5.1 events per patient year exposure; p<0.001).
There was a 57% lower rate of confirmed hypoglycaemia with Xultophy® compared with insulin glargine (2.23 episodes/patient-year vs 5.05 episodes/patient-year; p<0.001). Additionally, there was a significant difference of 3.2 kg (7.1 lb) in change in body weight between treatment groups (p<0.001); body weight decreased by 1.4 kg (3.0 lb) from baseline for patients treated with Xultophy® and increased by 1.8 kg (4.0 lb) for patients treated with insulin glargine.
Patients treated with Xultophy® required significantly less insulin than patients treated with insulin glargine, demonstrated by the end-of- trial dose of 41 units of the insulin degludec component in Xultophy® versus 66 units respectively (p<0.001). In the DUAL™ V trial, there were similar rates of overall and serious adverse events in the two treatment groups.
