Novo Nordisk New Data From a Phase 3 Study Confirms Clinical Benefits of Once-Daily Liraglutide in the Management of Type 2 Diabetes

Update: Victoza (liraglutide) Now FDA Approved - January 25, 2010

ROME, September 08, 2008 /PRNewswire-FirstCall/ -- 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 <7.0% compared to 28% of those who received placebo. Likewise, more than 35% of the patients in the liraglutide groups reached HbA1c < or = 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, 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.

 


                          Liraglutide          Liraglutide
                          1.2 mg +             1.8 mg +          Placebo +
                          metformin +          metformin +       metformin +
                          rosiglitazone        rosiglitazone     rosiglitazone
                          N=178                N=178             N=177

    Final HbA1c, %
     Change HbA1c from      7.0                  7.1               7.9
     baseline % points    -1.48*               -1.48*             -0.5

    % HbA1c achieving
     <7.0%                   58*                  54*               28

    % HbA1c achieving
     < or = 6.5%             36*                  37*               14

    Mean change in weight
     from baseline, kg     -1.02*               -2.02              0.60

    Mean change in
     FPG from baseline,
     mmol/L                -2.2*                -2.4*             -0.4

    Mean change in
     PPG from baseline,
     mmol/L                -2.6                 -2.7*             -0.8

    % reporting minor
     hypoglycemic          9                    8                 5
     events/subject/year   0.38                 0.64*             0.17

    Mean change in
     systolic blood
     pressure from
     baseline, mmHg        -6.7*                -5.6*             -1.1

    *p<0.05 versus placebo
    FPG, fasting plasma glucose; OAD, oral antidiabetic drug; PPG,
     post-prandial glucose

Safety and tolerability of liraglutide

There were no major hypoglycemic episodes reported during the study. The rate of minor hypoglycemia (<3.1 mmol/L) was low in all groups (0.38, 0.64 and 0.17 events per subject year with liraglutide 1.2 mg, 1.8 mg and placebo, respectively). The most frequent adverse event was nausea, which was reported by 29-40% of patients treated with 1.2 mg and 1.8 mg respectively. However, nausea levels decreased to the same as the placebo group after the first 16 weeks of the study and it was not a major reason for discontinuation during the trial.

About liraglutide

Once-daily liraglutide is the first human Glucagon-Like Peptide-1 (GLP-1) analog developed for the treatment of type 2 diabetes. Liraglutide works by stimulating the release of insulin only when glucose levels become too high and by inhibiting appetite. On May 23, 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the US as well as a marketing authorization application to the European Medicines Agency in Europe, for the approval of liraglutide for the treatment of people with type 2 diabetes. A New Drug Application was also submitted for approval in Japan on July 15, 2008.

About LEAD(TM) (Liraglutide Effect and Action in Diabetes)

The LEAD(TM) program includes five randomized, controlled, double-blind phase 3a studies, involving about 4,000 people with type 2 diabetes in 40 countries.

Novo Nordisk is a healthcare company with an 85-year history of innovation and achievement in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition to diabetes care, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk's business is driven by the Triple Bottom Line: a commitment to economic success, environmental soundness, and social responsibility to employees and customers. With headquarters in Denmark, Novo Nordisk employs more than 26,000 employees in 80 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO'. For global information, visit novonordisk.com; for United States information, visit www.novonordisk-us.com.

CONTACT: Media: An Phan, +1-609-558-0420, or Investors: Mads VeggerbyLausten, +45-4443-7919, both for Novo Nordisk

Web site: http://novonordisk.com/http://www.novonordisk-us.com/

Ticker Symbol: (NYSE:NVO)

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Posted: September 2008

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