Novo Nordisk New Data From a Phase 3 Study Confirms Clinical Benefits of Once-Daily Liraglutide in the Management of Type 2 Diabetes
ROME, Sep 08, 2008 -- Novo Nordisk, a global healthcare company, presented data from a phase 3 clinical study (LEAD(TM) 4) today at the 44th annual meeting of the European Association for the Study of Diabetes that demonstrated adding the investigational new drug liraglutide, a human GLP-1 analog, to metformin and rosiglitazone in the treatment of type 2 diabetes, leads to improved blood glucose lowering (HBA1c), weight loss, blood pressure reduction and improvements in beta-cell functioning.
Participants in the study were randomized to receive liraglutide (1.8 mg or 1.2 mg dose) or placebo for 26 weeks in addition to metformin and rosiglitazone. Treatment with liraglutide in addition to metformin and rosiglitazone resulted in a mean reduction of 1.5% from baseline HbA1c. Fasting blood glucose levels decreased by 2.4 mmol/L within two weeks on 1.8 mg of liraglutide. More than half of the patients who received liraglutide reached the American Diabetes Association HbA1c target of less than 7.0% compared to 28% of those who received placebo. Likewise, more than 35% of the patients in the liraglutide groups reached HbA1c less than or equal to 6.5% compared to 14% in the placebo group. In both cases, the difference between the groups receiving liraglutide and the group treated with metformin and rosiglitazone alone was statistically significant.
In addition to improved glucose lowering, liraglutide treatment also led to significant weight loss. Mean body weight decreased significantly for liraglutide compared to an increase in weight of 0.6 kg in the metformin and rosiglitazone only group. Weight is a common problem among individuals with type 2 diabetes and is one of the most challenging aspects in managing this condition. Paradoxically, many of the common treatment regimens for type 2 diabetes actually cause weight gain.
Treatment with liraglutide in LEAD(TM) 4 also led to a statistically significant decrease in blood pressure as seen in three of the other LEAD(TM) studies: reductions of 6.71 mmHg and 5.65 mmHg with liraglutide 1.2 mg and 1.8 mg, respectively, were observed compared to a decrease of 1.11 mmHg in the comparator group.
Beta cell function, as assessed by multiple parameters (HOMA, C-peptide and proinsulin to insulin ratio), was also significantly improved in subjects who received liraglutide versus the comparator group. Beta cell function is an important measure of disease progression in type 2 diabetes.
LEAD(TM) 4 is the last of the five phase 3a LEAD(TM) (Liraglutide Effect and Action in Diabetes) studies to be presented.
"The complete LEAD(TM) clinical trials program provides convincing evidence that liraglutide represents an effective new treatment approach for type 2 diabetes," said Dr. Bernard Zinman, Professor of Medicine, University of Toronto and Director of the Diabetes Centre Mount Sinai Hospital, Toronto, Canada. "In this clinical trial program, liraglutide offers effective glucose lowering as monotherapy or as an add on to other oral antidiabetic therapies while also consistently lowering weight and blood pressure and enhancing beta-cell function."
About the study
The LEAD(TM) 4 study was a 26-week randomized trial that compared the efficacy and safety of two different doses of liraglutide (1.2 mg and 1.8 mg, QD) to placebo, all added to metformin 2 g (1 g, BID) and rosiglitazone 8 mg (4 mg, BID). The trial included 533 subjects with a mean age of 55.1 years, mean body mass index of 33.5 kg/m2, and mean HbA1c of 8.3. All subjects were previously treated with one or more OADs and received run-in rosiglitazone and metformin therapy before being randomized to liraglutide or placebo.