Date: 2014-06-14
Type of information: Presentation of results at a congress
phase: 3a
Announcement: presentation of results at the 74th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, CA.
Company: Novo Nordisk (Denmark)
Product: Xultophy®/IDegLira® (combination of insulin degludec (Tresiba®) and liraglutide (Victoza®))
Action
mechanism: 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.
Disease: type 2 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial
details: DUAL™ (DUal Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) consists of two phase 3a trials encompassing around 2,000 people with type 2 diabetes.
DUAL™ I (1,663 people) – a 26-week, randomised, parallel, three-arm, open-label, multicentre, trial conducted at 271 sites across 19 countries. The trial compared the efficacy and safety of IDegLira versus insulin degludec and liraglutide alone, in insulin-naïve adults with type 2 diabetes uncontrolled with metformin with or without pioglitazone. A 26-week extension phase of the main trial was conducted to generate longer-term safety and efficacy data.
DUAL™ II (398 people) is a 26-week, randomised, parallel, two-arm, double-blinded, multicentre, trial conducted at 75 sites across seven countries. Around 400 patients with type 2 diabetes, previously inadequately controlled on basal insulin in combination with 1–2 oral anti-diabetic agents, were randomised to 26 weeks of double-blinded treatment with either IDegLira or Tresiba®, in addition to metformin. In agreement with regulatory requirements, the maximum dose of Tresiba® in the trial was fixed in both treatment arms, to investigate the additional impact of the liraglutide component of the IDegLira product on glucose control.
Latest
news: * On June 14, 2014, Novo Nordisk announced that new Phase 3a findings shows IDegLira®, the once daily single injection combination of Tresiba® (insulin degludec) and Victoza® (liraglutide) for the treatment of people with type 2 diabetes, maintained its glucose-lowering effect and confirmed safety evaluations for up to one year.1 Findings from the 26-week extension of the DUAL™ I clinical trial programme were presented at the 74th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco. The DUAL™ I extension trial compared the efficacy and safety of IDegLira with insulin degludec and liraglutide 1.8 mg alone in insulin-naïve adults with type 2 diabetes uncontrolled on metformin with or without pioglitazone. At 52 weeks, IDegLira demonstrated a statistically significant and sustained HbA1c (blood glucose) reduction of 1.8% from baseline versus 1.4% for insulin degludec and 1.2% for liraglutide (p<0.0001). The average HbA1c at the end of the trial was 6.4% for IDegLira, 6.9% with insulin degludec and 7.1% with liraglutide. Of the patients on IDegLira, 78% achieved an HbA1c goal of <7% versus 63% for insulin degludec and 57% for liraglutide. Mean fasting plasma glucose (FPG) was similar for IDegLira (103 mg/dl) and insulin degludec (108 mg/dl) and higher for liraglutide (132 mg/dl). * On December 19, 2012, Novo Nordisk has announced the completion of the phase 3a programme for IDegLira®, a fixed-ratio combination of insulin degludec (Tresiba®), a once-daily new-generation basal insulin analogue, with an ultra-long duration of action, and liraglutide (Victoza®), the once-daily human GLP-1 analogue. DUAL™ II, the second and final phase 3a trial with IDegLira for the treatment of patients with type 2 diabetes, has been completed. After 26 weeks, patients randomised to Tresiba® arm, with a fixed maximum dose, obtained blood glucose control as expected from the findings in the phase 3a programme BEGIN™, while patients randomised to IDegLira® experienced a reduction in HbA1c of 1.9% from baseline. The difference in HbA1c reduction between the treatment groups was statistically significant, and the trial thus met its primary endpoint of achieving superiority compared to stand-alone therapy with Tresiba®. Starting from a baseline HbA1c of 8.7%, approximately 60% of patients using IDegLira® achieved the HbA1c treatment target of 7% recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), and 45% reached HbA1c target of 6.5% as recommended by the American Academy of Clinical Endocrinology (AACE). The rate of overall hypoglycaemia was low in both treatment arms and comparable to what has been observed in previous studies. Furthermore, patients treated with IDegLira® experienced a weight loss of approximately 2.5 kg. The previously reported safety and tolerability profiles of IDegLira and Tresiba® were confirmed and no apparent differences between the treatment groups were observed with respect to adverse events and standard safety parameters. Together with the results from DUAL™ I, for which headline data were announced in August 2012, DUAL™ II reconfirms the competitive profiles of Tresiba® and Victoza®, and the trials show that patients can realise benefits from each of the components in the combination product. Pending marketing authorisations of Tresiba®, Novo Nordisk is planning regulatory filing for IDegLira® in the EU and in US during 2013.
At the end of the trial, the IDegLira treatment group observed a mean weight reduction of 0.4 kg/0.9 lbs, which was consistent with the first 26 weeks of treatment. Patients taking insulin degludec had a weight gain of 2.3 kg/5.1 lbs and patients on liraglutide had a weight reduction of 3.0 kg/6.6 lbs. The estimated treatment difference between IDegLira and insulin degludec was -2.8 kg/6.1 lbs and the relative treatment difference between IDegLira and liraglutide was 2.7 kg/5.9 lbs.
The daily insulin dose for patients on IDegLira remained stable throughout the extension phase (39 units) compared with insulin degludec (62 units). Patients treated with IDegLira had a 37% lower rate of hypoglycaemia versus insulin degludec (p<0.0001) whereas liraglutide was associated with less hypoglycaemia.
