Novo Nordisk has announced clinical results from the second and third of five phase III 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 per cent 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 per cent of patients reaching the American Diabetes Association goal of HbA1c < 7 per cent 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 per cent 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 per cent of patients achieved the HbA1c target of 7 per cent. Among patients previously treated with a single oral antidiabetic drug, close to 65 per cent 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 per cent and 20 per cent 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 III 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.
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 III development.