Liraglutide improves glucose control and lowers body weight in two phase 3 studies comprising more than 2,000 patients (20 Aug 2007)
Novo Nordisk today announced clinical results from the second and third of five phase 3 studies with liraglutide - the once-daily human GLP-1 analogue. The two 26-week studies are part of the LEAD® (Liraglutide Effect and Action in Diabetes) programme and comprised 2,132 patients in total. The two studies investigated the effect of different doses of liraglutide in combination with a single oral antidiabetic drug. Patients inadequately controlled by one or two oral antidiabetic drugs could enter the studies.
After a run-in period to reach the maximal dose of glimepiride, patients in the LEAD® 1 study were randomised to treatment with placebo, rosiglitazone or liraglutide. Likewise, after a run-in period to reach the maximal dose of metformin, patients in the LEAD® 2 trial were randomised to treatment with placebo, glimepiride or liraglutide. Consequently, liraglutide treatment in the two studies represented either add-on to previous monotherapy or substitution of one oral antidiabetic drug. In both trials, the average HbA1c level at the beginning of the study was just below 8.5% and the average body weight was 80 to 90 kg.
In the LEAD® 1 study, liraglutide provided statistically significantly better glucose control than rosiglitazone. Liraglutide treatment led to around 40% of patients reaching the American Diabetes Association goal of HbA1c < 7% at study completion. However, among the patients that had previously been treated with only a single oral antidiabetic drug, liraglutide treatment led to more than 50% of patients reaching this goal. These success rates were the result of an HbA1c reduction of approximately 1 to 1.5 percentage points. As would be expected from a study in which all patients received glimepiride treatment, hypoglycaemia related to the degree of blood glucose control was observed in all study arms.
In the LEAD® 2 study, liraglutide treatment led to an HbA1c improvement that was similar to that observed in the glimepiride-treated group and at the highest dose of liraglutide, more than 40% of patients achieved the HbA1c target of 7%. Among patients previously treated with a single oral antidiabetic drug, close to 65% of the patients on this dose reached the target. These success rates were the result of an HbA1c reduction of between 1 and 1.5 percentage points. In the LEAD® 2 study, liraglutide-treated patients achieved blood glucose control in the presence of hypoglycaemia rates similar to placebo, contrasting with the glimepiride-treated group where hypoglycaemia occurred in a larger number of patients.
At the end of the LEAD® studies, a weight difference of between 2 and 4 kg in favour of liraglutide was found when compared to rosiglitazone and glimepiride treatment, respectively.
Liraglutide in combination with glimepiride or metformin was well tolerated. The most frequently reported adverse event during liraglutide treatment was nausea at an absolute level of between 5% and 20% when used in combination with glimepiride and metformin.
Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, said: "The encouraging clinical results from the two new trials confirm the positive effect of liraglutide on blood glucose control, body weight and hypoglycaemia risk seen in previous studies and leave us confident that we are on track to submit for regulatory approval mid-2008."
Novo Nordisk expects to announce headline results from the remaining two LEAD® studies during the second half of 2007 and the first quarter of 2008. Detailed results from the full LEAD® programme are expected to be published in peer reviewed journals and communicated at future scientific meetings.
The results of the phase 3 trial do not change Novo Nordisk's expectations for the company's financial results for 2007, which were provided on 3 August in connection with the release of the financial results for the first six months of 2007.
About liraglutide, LEAD® and HbA1c
Liraglutide is a once-daily human analogue of the naturally occurring hormone Glucagon-Like Peptide-1 (GLP-1). The compound is being developed by Novo Nordisk for the treatment of type 2 diabetes, and is currently in phase 3 development. Liraglutide works by stimulating the release of insulin only when glucose levels become too high. In contrast to most other antidiabetic treatments, liraglutide also leads to weight loss instead of weight increase.
The LEAD® programme (Liraglutide Effect and Action in Diabetes) is comprised of five randomised, controlled, double-blind studies conducted in more than 40 countries. The programme includes around 3,800 patients with type 2 diabetes whose blood glucose is inadequately controlled.
HbA1c is an abbreviation for glycated haemoglobin HbA1c. The level of HbA1c reflects the average blood glucose level over the past two to three months and a decrease is therefore a measure of treatment effect. The higher the blood glucose the more glucose binds to haemoglobin (glycation
Liraglutide provides significantly better glucose control than insulin glargine in phase 3 study (21 Jun 2007)
Novo Nordisk today announced clinical results from the first of five phase 3 studies with liraglutide - the once-daily human GLP-1 analogue. The 26-week study is part of the LEAD(TM) (Liraglutide Effect and Action in Diabetes) programme and included 581 patients with type 2 diabetes inadequately controlled by two of the most widely used oral antidiabetic drugs: metformin and a sulfonylurea (glimepiride). All patients in the study continued the two oral drugs and were randomised to add one daily injection of liraglutide, placebo or insulin glargine.
The average HbA1c level at the beginning of the study was between 8.0% and 8.5% and at the end of the study, more than 50% of patients in the liraglutide group had reached the American Diabetes Association goal of HbA1c < 7%. Furthermore, more than 35% achieved the American Association of Clinical Endocrinologists HbA1c target of <= 6.5%. The HbA1c reduction achieved in the liraglutide group was more than 0.2 percentage points better than in the insulin glargine group, a difference which is statistically significant.
The average weight of the patients at the beginning of the study was approximately 85 kg. At the end of the study, the difference in body weight between the liraglutide and insulin glargine treatment groups was on average 3.5 kg, statistically significant in favour of liraglutide.
Liraglutide in combination with metformin and glimepiride was well tolerated. The most frequently reported adverse event in the liraglutide arm was nausea at an absolute level of between 10 and 15%. As expected, the combination of a GLP-1 analogue with a sulfonylurea leads to some of the patients experiencing hypoglycaemia. The overall hypoglycaemia event rate in the liraglutide and insulin glargine groups was not significantly different.
Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, said: "We are very pleased with these first results from the liraglutide phase 3 programme, showing that liraglutide provides improved glucose control compared to insulin glargine while, at the same time, leading to significant weight loss."
Novo Nordisk expects to announce headline results from the remaining four LEAD(TM) studies during the second half of 2007 and the first quarter of 2008. Detailed results from the full LEAD(TM) programme are expected to be published in peer reviewed journals and communicated at future scientific meetings.
The results of the phase 3 trial do not change Novo Nordisk's expectations for the company's financial results for 2007, which were provided on 2 May in connection with the release of the financial results for the first three months of 2007.
Conference call
At 12.30 pm CET today, corresponding to 6.30 am EDT, a conference call for investors will be held. Investors will be able to listen in via a link on novonordisk.com, which can be found under 'Investors - Download centre'.
About liraglutide, LEAD(TM) and HbA1c
Liraglutide is a once-daily human analogue of the naturally occurring hormone Glucagon-Like Peptide-1 (GLP-1). The compound is being developed by Novo Nordisk for the treatment of type 2 diabetes, and is currently in phase 3 development. Liraglutide works by stimulating the release of insulin only when glucose levels become too high. In contrast to most other antidiabetic treatments liraglutide also leads to weight loss instead of weight increase.
The LEAD(TM) programme (Liraglutide Effect and Action in Diabetes) is comprised of five randomised, controlled, double-blind studies conducted in more than 40 countries. The programme includes around 3,800 patients with type 2 diabetes whose blood glucose is inadequately controlled.
HbA1c is an abbreviation for glycated haemoglobin HbA1c. The level of HbA1c reflects the average blood glucose level over the past 2-3 months and a decrease is therefore a measure of treatment effect. The higher the blood glucose the more glucose binds to haemoglobin (glycation).