ROME, Sept. 8 Novo Nordisk (NYSE: NVO), a globalhealthcare 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 ofDiabetes that demonstrated adding the investigational new drug liraglutide, ahuman GLP-1 analog, to metformin and rosiglitazone in the treatment of type 2diabetes, leads to improved blood glucose lowering (HbA1c), weight loss, bloodpressure reduction and improvements in beta-cell functioning.
Participants in the study were randomized to receive liraglutide (1.8 mgor 1.2 mg dose) or placebo for 26 weeks in addition to metformin androsiglitazone. Treatment with liraglutide in addition to metformin androsiglitazone 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 1.8mg of liraglutide. More than half of the patients who received liraglutidereached the American Diabetes Association HbA1c target of <7.0% compared to28% of those who received placebo. Likewise, more than 35% of the patients inthe liraglutide groups reached HbA1c < or = 6.5% compared to 14% in theplacebo group. In both cases, the difference between the groups receivingliraglutide and the group treated with metformin and rosiglitazone alone wasstatistically significant.
In addition to improved glucose lowering, liraglutide treatment also ledto significant weight loss. Mean body weight decreased significantly forliraglutide compared to an increase in weight of 0.6 kg in the metformin androsiglitazone only group. Weight is a common problem among individuals withtype 2 diabetes and is one of the most challenging aspects in managing thiscondition. Paradoxically, many of the common treatment regimens for type 2diabetes actually cause weight gain.
Treatment with liraglutide in LEAD(TM) 4 also led to a statisticallysignificant 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 1.8mg, respectively, were observed compared to a decrease of 1.11 mmHg in thecomparator group.
Beta cell function, as assessed by multiple parameters (HOMA, C-peptideand proinsulin to insulin ratio), was also significantly improved in subjectswho received liraglutide versus the comparator group. Beta cell function isan important measure of disease progression in type 2 diabetes.
LEAD(TM) 4 is the last of the five phase 3a LEAD(TM) (Liraglutide Effectand Action in Diabetes) studies to be presented.
"The complete LEAD(TM) clinical trials program provides convincingevidence that liraglutide represents an effective new treatment approach fortype 2 diabetes," said Dr. Bernard Zinman, Professor of Medicine, Universityof Toronto and Director of the Diabetes Centre Mount Sinai Hospital, Toronto,Canada. "In this clinical trial program, liraglutide offers effective glucoselowering as monotherapy or as an add on to other oral antidiabetic therapieswhile also consistently lowering weight and blood pressure and enhancingbeta-cell function."
About the study
The LEAD(TM) 4 study was a 26-week randomized trial that compared theefficacy 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 werepreviously treated with one or more OADs and received run-in rosiglitazone andmetformin therapy before being randomized to liraglutide or placebo.
Safety and tolerability of liraglutide
There were no major hypoglycemic episodes reported during the study. Therate of minor hypoglycemia (<3.1 mmol/L) was low in all groups (0.38, 0.64 and0.17 events per subject year with liraglutide