Liraglutide Press Releases - a once-daily human GLP-1 analogue

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Liraglutide Press Releases

• Novo Nordisk today announced clinical results from a 32-week open-label extension of a 20-week phase 2 obesity study, in which treatment with liraglutide, the once-daily human GLP-1 analogue, was tested in obese people without diabetes. Novo Nordisk reported headline results from the initial 20 weeks of the phase 2 study in November 2007.
  
  398 of the 564 participants in the original 20-week, double-blind, placebo-controlled phase 2 study comparing liraglutide with open-label orlistat, a lipase inhibitor, continued into the 32-week extension. Treatment allocation from the initial 20 weeks was maintained in the extension period.
  
  After 52 weeks, liraglutide given once daily at the highest dose led to a mean weight loss from baseline of around 7.5-8.0 kg and a placebo-adjusted weight loss of around 5.5-6.0 kg, compared to a weight loss after 20 weeks of just above 7 kg from baseline and 4.5 kg placebo-adjusted. Around 75% of the people treated with the highest dose achieved a weight loss larger than 5% and more than 35% achieved a weight loss larger than 10% after 52 weeks of treatment compared to around 25% and around 10%, respectively, reaching the same weight loss targets with placebo. The people treated with open-label orlistat lost 3.5-4.0 kg from baseline and around 45% and around 15% achieved a weight loss larger than 5% and 10% after 52 weeks of treatment, respectively.
  
  Of all patients participating in the extension study, around 30% showed signs of prediabetes at randomisation. After one year of being treated, around 80% of this prediabetes subgroup of patients treated with the highest dose of liraglutide no longer showed any signs of prediabetes, compared to around 30% for the placebo and orlistat-treated groups.
  
  Liraglutide was generally well tolerated and the proportion of people that withdrew due to side effects was below 15%. Consistent with all previous trials, the most common adverse events were related to the gastrointestinal system and mainly rated as mild to moderate. The most frequently reported individual adverse event was nausea observed with a frequency decreasing over time.
  
  Mads Krogsgaard Thomsen, executive vice president and chief science officer, said: "The results of the extension of the phase 2 obesity study clearly demonstrates that liraglutide has a sustained ability to reduce body weight while at the same time providing protection against deteriorating glycaemic control."
  
  Novo Nordisk still expects to initiate a phase 3 programme in obese people without diabetes before the end of 2008. The results of the study do not impact Novo Nordisk's expectations for the company's financial results for 2008, which were provided on 30 April in connection with the release of the financial results for the first quarter of 2008.
  
  About the study design
  After an initial run-in period of two weeks with dietary advice and daily injections of placebo, 564 people with an average baseline weight of just below 100 kg were randomised to either placebo, to increasing doses of liraglutide or to an open-labelled control arm with orlistat for a treatment period of 20 weeks. After 20 weeks, 398 of the participants volunteered to continue into an open-label extension in which all participants continued on existing therapy for an additional 32 weeks.
  
  About prediabetes
  Prediabetes is characterised by either increased levels of fasting glucose (Impaired Fasting Glucose) or increased levels of glucose in a glucose tolerance test (Impaired Glucose Tolerance) that are too high to be considered normal, but not high enough to meet the criteria for diagnosis of diabetes. People with prediabetes are at a higher risk of developing both cardiovascular disease and actual diabetes. Prediabetes is often associated with the so-called metabolic syndrome which in addition to high blood glucose levels include abdominal obesity, abnormal blood lipid levels and elevated blood pressure.
  
  About treatment of obesity with liraglutide
  Obesity is an increasing global problem which is associated with increased risk of developing type 2 diabetes and other serious conditions. It is generally agreed that the best way to tackle obesity is through exercise and healthy diets. It is, however, also recognised that for some people it is difficult to achieve and maintain the needed weight reduction even with substantial efforts. Thus, in people who are at high risk of getting obesity-related complications, for example patients with additional risk factors such as osteoarthritis, hypertension, cardiovascular disease or prediabetes, adjunctive treatment with medicine may be needed to reduce the risk of complications and improve the quality of life.
  
  About liraglutide
  Liraglutide is a once-daily human GLP-1 analogue. Liraglutide works by stimulating the release of insulin only when glucose levels become too high and by inhibiting appetite. On 23 May 2008, Novo Nordisk submitted a New Drug Application to the US Food and Drug Administration as well as a marketing authorisation application to the European Medicines Agency, for the approval of liraglutide for the treatment of people with type 2 diabetes. Novo Nordisk is a healthcare company and a world leader in diabetes care. In addition, Novo Nordisk has a leading position within areas such as haemostasis management, growth hormone therapy and hormone replacement therapy. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs approximately 26,300 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'.

• Phase 3 data highlight sustained efficacy and benefits of early treatment with liraglutide versus glimepiride (San Francisco, USA) – Data presented over the weekend at the 68th Scientific Sessions of the American Diabetes Association (ADA) demonstrated that once-daily liraglutide when taken alone produced statistically significant improvement in blood sugar (glucose) control in patients with type 2 diabetes, as compared to glimepiride, a widely used oral antidiabetic drug (OAD).
  
  In addition, liraglutide demonstrated the following benefits compared to glimepiride: - Statistically significant reduction in body weight - Statistically significant reduction in risk of hypoglycaemia - Statistically significant reduction in systolic blood pressure.
  
  In this 12-month study, 62% of patients treated with liraglutide who had not been previously treated with diabetes medications achieved an average reduction in blood sugar that brought them below the ADA target for HbA1c of 7%.
  
  "This study showed that when used as initial drug treatment for type 2 diabetes, once-daily liraglutide not only statistically significantly reduced blood glucose, weight and systolic blood pressure, but sustained blood glucose reductions for the duration of the study in patients who had never taken diabetes medications before," said study investigator Robert E Ratner, MD, vice president for Scientific Affairs at the MedStar Research Institute in Washington, DC.
  
  "The sustained reduction in blood glucose suggests that liraglutide may be beneficial when used earlier in the course of diabetes."
  
  More about the Liraglutide study.

• Novo Nordisk today announced headline clinical results from a phase 3 clinical study (LEAD(TM) 6) comparing the effects of liraglutide, a once-daily human GLP-1 analogue, with exenatide, a twice-daily GLP-1 analogue. The 26-week study, which is the first study to provide a direct comparison between the two GLP-1 analogues, included 464 people with type 2 diabetes who were randomised to treatment with either liraglutide once daily or exenatide twice daily, as add-on to their existing treatment consisting of metformin, sulfonylurea, or a combination of both.
  
  The average HbA1c level at the beginning of the study was slightly above 8% and the primary endpoint was the change in HbA1c. Patients treated with liraglutide achieved a reduction in HbA1c of more than 1.1 percentage points, compared to a reduction in HbA1c of less than 0.8 percentage points in the exenatide group, a difference which was statistically significant. Liraglutide treatment led to statistically significantly more patients achieving both the American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) HbA1c targets of <7% and="and" < ="6.5%," respectively.="respectively." specifically,="specifically," 55%="55%" group="group" reached="reached" ada="ada" close="close" 45%="45%" in="in" exenatide="exenatide" group.="group." likewise,="likewise," 35%="35%" of="of" liraglutide="liraglutide" achieved="achieved" the="the" aace="aace" target,="target," compared="compared" to="to" around="around" 20%="20%" for="for" patients="patients" treated="treated" with="with" exenatide.="exenatide." <br="&lt;br">
  The patients' average weight at the beginning of the study was between 90 and 95 kg. Both patients treated with liraglutide and patients treated with exenatide lost on average around 3 kg during the course of the study, with a trend towards more weight loss in the liraglutide group. Among patients previously treated with metformin alone, this difference was 1 kg in favour of liraglutide (not statistically significant).
  
  The most frequently reported adverse event for both liraglutide and exenatide was nausea at a level of around 25% (percent of all study participants reporting nausea at least once). In the liraglutide group, the percentage of patients reporting nausea in each week fell to low single-digit numbers after 8-10 weeks, similar to the level observed in a background population. In the exenatide group, the level after 8-10 weeks of treatment remained at the level of 10%.
  
  As expected, the overall rate of hypoglycaemia in the study was low. The rate of minor hypoglycaemia was statistically significantly lower in the liraglutide group, compared to the exenatide group.
  
  Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, said: "We are very encouraged by the fact that the study showed that once-daily liraglutide leads to statistically significantly better blood glucose control than twice-daily exenatide. In addition, liraglutide treatment leads to weight loss and is associated with a very low risk of hypoglycaemia."
  
  The results of the phase 3 trial do not impact Novo Nordisk's expectations for the company's financial results for 2008, which were provided on 30 April in connection with the release of the financial results for the first quarter of 2008.
  
  About liraglutide and HbA1c
  Liraglutide is a once-daily human GLP-1 analogue. Liraglutide works by stimulating the release of insulin only when glucose levels become too high and by inhibiting appetite. On 23 May 2008, Novo Nordisk submitted a New Drug Application to the US Food and Drug Administration as well as a marketing authorisation application to the European Medicines Agency, for the approval of liraglutide for the treatment of people with type 2 diabetes.
  
  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).
  
  Novo Nordisk is a healthcare company and a world leader in diabetes care. In addition, Novo Nordisk has a leading position within areas such as homeostasis management, growth hormone therapy and hormone replacement therapy. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs approximately 26,300 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'.

• Novo Nordisk today announced the submission of a New Drug Application (NDA) to the Food and Drug Administration (FDA) in the US as well as a marketing authorisation application to the European Medicines Agency (EMEA) in Europe, for the approval of liraglutide, a once-daily human GLP-1 analogue, for the treatment of people with type 2 diabetes.
  
  Both the US and the European applications contain documentation from an extensive clinical development programme that included around 6,500 people of which approximately 4,200 received liraglutide. The programme was designed to obtain the indication for use of liraglutide to treat type 2 diabetes as an adjunct to diet and exercise, both as monotherapy and in combination with commonly used antidiabetic medications. The majority of people were included in the phase 3 trials constituting the LEAD(TM) (Liraglutide Effect and Action in Diabetes) programme. The LEAD(TM) programme has compared liraglutide with three widely used classes of antidiabetic drugs - sulfonylurea, glitazone or basal insulin - and the programme confirmed a statistically significant benefit of liraglutide on the primary endpoint, lowering of blood glucose (HbA1c), as well as on the secondary endpoint, weight loss.
  
  Mads Krogsgaard Thomsen, executive vice president and chief science officer at Novo Nordisk, said: "This is a major achievement for Novo Nordisk and it represents a huge amount of work done by Novo Nordisk employees and our collaborators across the world. We are very pleased with the results from the programme demonstrating that liraglutide will be able to offer benefits to people with type 2 diabetes. We are enthusiastic about the prospect of bringing liraglutide to market after completion of the regulatory process."
  
  Novo Nordisk still expects to file for marketing approval of liraglutide in Japan in the third quarter of 2008.
  
  The submission of liraglutide in the US and Europe does not impact Novo Nordisk's expectations for the company's financial results for 2008, which were provided on 30 April in connection with the release of the financial results for the first quarter of 2008.
  
  About liraglutide, LEAD(TM) and HbA1c
  Liraglutide is a once-daily human analogue of the naturally occurring hormone Glucagon-Like Peptide-1 (GLP-1). Liraglutide works by stimulating the release of insulin only when glucose levels become too high and by inhibiting appetite. In contrast to most other antidiabetic treatments, liraglutide also leads to weight loss instead of weight increase.
  
  The portfolio of LEAD(TM) studies for liraglutide included around 4,000 patients with type 2 diabetes whose blood glucose is inadequately controlled. The programme was comprised of five randomised, controlled, double-blind studies conducted in more than 40 countries.
  
  The LEAD(TM) 1 and LEAD(TM) 2 studies investigated the effect of different doses of liraglutide in combination with a single oral antidiabetic drug, glimepiride and metformin respectively. The LEAD(TM) 3 study compared the effect of liraglutide with glimepiride when used as monotherapy.
  
  The LEAD(TM) 4 study investigated the effect of different doses of liraglutide in combination with metformin and rosiglitazone. The LEAD(TM) 5 study compared the effect of liraglutide with insulin glargine when used as add-on therapy in patients inadequately controlled by two of the most widely used oral antidiabetic drugs: metformin and a sulfonylurea (glimepiride).
  
  At the annual meeting of the American Diabetes Association (ADA) to be held in San Francisco on 6-10 June 2008, Novo Nordisk will present detailed results from the LEAD(TM) phase 3 programme with liraglutide. 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).
  
  Novo Nordisk is a healthcare company and a world leader in diabetes care. In addition, Novo Nordisk has a leading position within areas such as haemostasis management, growth hormone therapy and hormone replacement therapy. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs approximately 26,300 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'.

• Novo Nordisk today announced clinical results from a one-year monotherapy study, the last of five phase 3 studies needed for regulatory filing, investigating liraglutide - the once-daily human GLP-1 analogue for treatment of type 2 diabetes.
  
  The study, which is part of Novo Nordisk's LEAD® programme (Liraglutide Effect and Action in Diabetes), included 746 patients with type 2 diabetes. Patients in the study were randomised to treatment with one of two doses of liraglutide or 8 mg (maximal dose) of glimepiride, a widely used oral antidiabetic medication.
  
  Approximately two thirds of the patients had previously been treated with one oral antidiabetic medication, while one third had only been treated with diet and exercise. This means that in this study liraglutide or glimepiride was given to some patients instead of the oral antidiabetic medication they had been taking previously, while others received liraglutide as their first diabetes medication. The average HbA1c level at the beginning of the study was around 8.2% and the average body weight was 90 to 95 kg.
  
  At both doses tested, liraglutide provided statistically significantly better glucose control than glimepiride. On average, the patients treated with liraglutide experienced a lowering of HbA1c of more than 1 percentage point, while those patients who had previously only been treated with diet and exercise saw HbA1c drop by more than 1.5 percentage points. The American Diabetes Association treatment goal of HbA1c < 7% was reached by more than 50% of the patients receiving the highest dose of liraglutide, while more than 60% of the patients previously treated with diet and exercise reached the target.
  
  As has been seen in previous studies where liraglutide has been given as monotherapy, patients receiving liraglutide in this study experienced a very low level of hypoglycaemia, contrasting with the glimepiride-treated group where hypoglycaemia occurred in a larger number of patients. Furthermore, a significant improvement in systolic blood pressure and a reduction of body weight of between 3 and 4 kg were seen in patients treated with liraglutide when compared to patients treated with glimepiride.
  
  Liraglutide in monotherapy was well tolerated. The most frequently reported adverse event during liraglutide treatment was transient, mild to moderate nausea at a cumulated absolute level of below 30% over the full year of treatment. After the first three months, the percentage of patients experiencing nausea was in the low single digit range.
  
  Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, said: "We are very pleased with the clinical results in this phase 3 study. They show that the benefits of liraglutide are sustainable after one year's treatment. All together, the phase 3 studies have compared liraglutide with three widely used classes of anti-diabetic drugs - sulfonylurea, glitazone and basal insulin - and have confirmed a statistically significant benefit of liraglutide on the primary endpoint, HbA1c, as well as on body weight."
  
  Novo Nordisk now expects to file for regulatory approval of liraglutide during the second 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 impact Novo Nordisk's expectations for the company's financial results for 2007, which were provided on 31 October in connection with the release of the financial results for the first nine months of 2007.
  
  Conference call
  At 5.00 pm CET today, corresponding to 11.00 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® 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 and by inhibiting appetite. 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) includes around 4,000 patients with type 2 diabetes whose blood glucose is inadequately controlled. The programme is comprised of five randomised, controlled, double-blind studies conducted in more than 40 countries:
  - The study reported on in this Stock Exchange Announcement is the LEAD 3 study.
  - Results from the LEAD® 5 study were reported on 21 June 2007. This study compared the effect of liraglutide with insulin glargine when used as add-on therapy in patients inadequately controlled by two of the most widely used oral antidiabetic drugs: metformin and a sulfonylurea (glimepiride).
  - Results from the LEAD® 1 and LEAD® 2 studies were announced on 20 August 2007. The two studies investigated the effect of different doses of liraglutide in combination with a single oral antidiabetic drug, glimepiride and metformin respectively.
  - Results from the LEAD® 4 study were announced on 14 September 2007. The study investigated the effect of different doses of liraglutide in combination with metformin and rosiglitazone.
  
  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).

• Novo Nordisk today announced clinical results from a double-blind, placebo-controlled phase 2 study comparing liraglutide, the once-daily human GLP-1 analogue, with orlistat, a lipase inhibitor, for treatment of obesity in people who do not have diabetes.
  
  The study demonstrated that liraglutide given once daily over 20 weeks at the highest dose led to a weight loss from baseline of just above 7 kg in comparison to a weight loss of just below 3 kg in the placebo group and a weight loss of just above 4 kg in the orlistat-treated group. All doses of liraglutide reduced body weight. More than 75% of the people treated with the highest dose experienced a weight loss larger than 5%, and more than 25% experienced a weight loss larger than 10% relative to their body weight at randomisation. Finally, the study revealed a beneficial effect on systolic blood pressure after treatment with liraglutide.
  
  Approximately 30% of the 564 participants in the study showed signs of prediabetes at randomisation. Following 20 weeks of treatment with any dose of liraglutide, between 80% and 90% of these participants no longer showed any sign of prediabetes, as opposed to around 40% in the placebo- and orlistat-treated groups.
  
  Liraglutide was generally well tolerated. The overall withdrawal rate across the study was around 20%, and no more than 10% of the people who were treated with liraglutide withdrew from the trial due to adverse events. Consistent with all previous trials, the most common adverse events were related to the gastrointestinal systems and mainly rated as mild to moderate. The most frequently reported individual adverse event was nausea. The frequency of events was dose dependent and in the range of 20% to 50%. Nausea was most frequently observed at the beginning of the study.
  
  In order to study the long-term weight reduction of liraglutide treatment, around 85% of all participants in the study volunteered to continue into an open label extension phase of the study.
  
  Mads Krogsgaard Thomsen, chief science officer, said: "We are very encouraged by these new results. They give us reason to believe that liraglutide has the potential to become a new and important treatment option in the fight against serious obesity."
  
  The results of the phase 2 trial do not change Novo Nordisk's expectations for the company's financial results for 2007, which were provided on 31 October in connection with the release of the financial results for the first nine months of 2007.
  
  Conference call
  
  At 15.00 CET today, corresponding to 9.00 am New York time, 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 the study design
  
  After an initial run-in period of two weeks with dietary advice and daily injections of placebo, study participants were randomised to either placebo, to increasing doses of liraglutide or to an open-labelled control arm with orlistat for a treatment period of 20 weeks. 564 people with an average baseline weight at randomisation of just below 100 kg entered the study.
  
  About prediabetes
  
  People with prediabetes are characterised by having either levels of fasting glucose (Impaired Fasting Glucose) or levels of glucose in a glucose tolerance test (Impaired Glucose Tolerance) that are too high to be considered normal, but not high enough to meet the criteria for diagnosis of diabetes. People with prediabetes are at a higher risk of developing both cardiovascular disease and actual diabetes. Prediabetes is often associated with the so-called metabolic syndrome which in addition to high blood glucose levels includes obesity, abnormal blood lipid levels and elevated blood pressure.
  
  About treatment of obesity with liraglutide
  
  Obesity is an increasing global problem, which is associated with increased risk of developing type 2 diabetes and other serious conditions. It is generally agreed that the best way to tackle obesity is through exercise and healthy diets. It is, however, also recognised that for some it is difficult to achieve and maintain the needed weight reduction even with substantial efforts. Thus, in people who are at high risk of getting obesity-related complications, for example patients with additional risk factors such as osteoarthritis, hypertension or cardiovascular disease, adjunctive treatment with medicine may be needed to reduce the risk of complications and improve quality of life.
  
  About liraglutide
  
  Liraglutide is Novo Nordisk's once-daily GLP-1 analogue, currently in phase 3 development for treatment of type 2 diabetes and phase 2 development for treatment of obesity. Results from four of five phase 3 studies in people with type 2 diabetes have been reported. The last study will be reported on around the turn of the year, and submission for regulatory approval for treatment of type 2 diabetes is expected mid 2008.

• Novo Nordisk today announced clinical results from the fourth of five phase 3 studies with liraglutide - the once-daily human GLP-1 analogue. The 26-week LEAD® 4 study is part of the LEAD® (Liraglutide Effect and Action in Diabetes) programme. The study investigated the effect of different doses of liraglutide in combination with metformin and rosiglitazone, and included 533 patients with type 2 diabetes.
  
  After a run-in period of metformin and rosiglitazone, patients in the study were randomised to add-on treatment with either liraglutide or placebo. The average HbA1c level at the beginning of the study was around 8.5% and the average body weight was just above 95 kg.
  
  At the end of the study, more than 50% of the patients in the liraglutide-treated 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-treated group was close to 1.5 percentage points compared to baseline. In addition, a weight difference of around 2.5 kg compared to placebo in favour of liraglutide was observed.
  
  Liraglutide in combination with metformin and rosiglitazone was well tolerated. The most frequently reported adverse event during liraglutide treatment was nausea, reported by around 30-40% of the subjects with a frequency decreasing over time. As expected, a low rate of hypoglycaemic events was reported, and these were related to the degree of blood glucose control.
  
  Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, said: "The new clinical results confirm the strong efficacy data in terms of glucose control with a low risk of hypoglycaemia together with weight loss that we have seen in the previously announced phase 3 trials. With data from now approximately 85% of all patients in the phase 3 programme, we are confident that liraglutide will become a valuable new treatment option for people with type 2 diabetes."
  
  Novo Nordisk expects to announce headline results from the last outstanding study (LEAD® 3) before the end of 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.
  
  Results from the LEAD® 5 study were reported on 21 June 2007. This study compared the effect of liraglutide with insulin glargine when used as add-on therapy in patients inadequately controlled by two of the most widely used oral antidiabetic drugs: metformin and a sulfonylurea (glimepiride).
  
  Results from the LEAD® 1 and LEAD® 2 studies were announced on 20 August 2007. The two studies investigated the effect of different doses of liraglutide in combination with a single oral antidiabetic drug, glimepiride and metformin respectively.
  
  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).

• 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).

• Novo Nordisk increased sales by 14% in local currencies and - due to a significant negative currency development - by 9% in Danish kroner.
  
  - Sales of modern insulins increased by 37% (31% in Danish kroner).
  - Sales of NovoSeven® increased by 11% (5% in Danish kroner).
  - Sales of Norditropin® increased by 13% (7% in Danish kroner).
  - Sales in North America increased by 25% (16% in Danish kroner).
  
  Gross margin increased to 77.0% in the first six months of 2007 up from 75.0% in the same period last year, primarily reflecting continued productivity improvements.
  
  Operating profit increased by 14% to DKK 5,134 million. Adjusted for the impact from currencies underlying operating profit increased by around 25%.
  
  Net profit increased by 81% to DKK 5,361 million, primarily reflecting the divestment of Dako's business activities. Earnings per share (diluted) increased by 84% to DKK 16.76.
  
  The full-year expectation for operating profit growth is now around 10%, primarily reflecting a sustainable improvement in gross margin. Measured in local currencies the expectation for full-year operating profit growth is now increased to around 20%.
  
  Novo Nordisk has announced very positive results from the first phase 3 study with liraglutide, a human GLP-1 analogue, showing that liraglutide is statistically superior to insulin glargine in terms of blood glucose control and weight loss.
  
  Lars Rebien Sørensen, president and CEO, said: "The business continues to perform very well with robust sales growth and a sustained improvement in our gross margin. We are also very pleased with the first phase 3 results on liraglutide which are expected to be supported by results from additional phase 3 studies during the following months."

• New study demonstrates 75% of patients receiving highest dose achieve HbA1c with no associated hypoglycaemia
  
  Chicago, IL – According to findings presented today at the 67th Scientific Sessions of the American Diabetes Association (ADA) in Chicago, Illinois the investigational treatment liraglutide, a once-daily dose of human GLP-1 analogue under development by Novo Nordisk for the treatment of type 2 diabetes significantly improved glycaemic control (HbA1c) by reducing both fasting and post-meal glucose levels in people with type 2 diabetes. The phase 2 study included 226 Japanese patients with type 2 diabetes treated over a period of 14 weeks. Results showed that liraglutide was effective and well tolerated within a wide dose range, allowing nearly 75% of patients receiving the highest dose to achieve glycaemic control (HbA1c<7.0%) without="without" hypoglycaemia.="hypoglycaemia." <br ="&lt;br">
  “One challenge with insulin and many oral antidiabetic agents, which boost insulin secretion or heighten insulin sensitivity, is that they can lower blood glucose levels, resulting in hypoglycaemia, which can sometimes be dangerous,” said Professor Yutaka Seino, director of Kansai-Denryoku Hospital and professor, Department of Metabolism & Clinical Nutrition, Graduate School of Medicine, Kyoto University, and lead investigator on the trial. “A well-tolerated agent with once-daily administration that can allow a majority of patients to achieve good glycaemic control with a low risk of hypoglycaemia and no weight gain is very promising and will be a considerable advance in diabetes treatment.”
  
  Liraglutide acts to lower blood glucose when levels are elevated, and previous studies have shown it is associated with a low risk of hypoglycaemia.
  
  About the Study (Abstract no 0520-P)
  
  In the study, 226 Japanese type 2 diabetes patients treated with diet or a single oral antidiabetic drug, discontinued any diabetes drug for an eight-week period. Patients were then randomised to receive one of four once-daily doses of liraglutide (0.1, 0.3, 0.6, and 0.9 mg) or placebo. Baseline HbA1c levels ranged between 8.1 to 8.5%. The randomised, 14-week study showed statistically significant dose-dependent reductions in HbA1c levels (ranging from 0.79 to 1.85 percentage points – placebo adjusted, p<0.0001) after="after" once-daily="once-daily" dosing="dosing" monotherapy="monotherapy" patients.="patients." further,="further," hba1c="hba1c" levels="levels" below="below" 7%="7%" were="were" achieved="achieved" by="by" 22,="22," 43,="43," 62="62" 75%="75%" patients="patients" liraglutide="liraglutide" 0.1,="0.1," 0.3,="0.3," 0.6="0.6" and="and" 0.9="0.9" mg/day="mg/day" compared="compared" with="with" 9%="9%" of="of" those="those" receiving="receiving" placebo.="placebo." additionally,="additionally," these="these" normal-weight="normal-weight" subjects="subjects" (average="(average" bmi="bmi" 23.9)="23.9)" no="no" relevant="relevant" changes="changes" body="body" weight="weight" major="major" or="or" minor="minor" hypoglycaemic="hypoglycaemic" events="events" occurred="occurred" in="in" any="any" study="study" group.<br ="group.&lt;br">
  The main gastrointestinal adverse events in the high dose group versus placebo were: constipation (7% versus 9%), diarrhoea (9% versus 4%), gastritis (7% versus 0%) and nausea (7% versus 2%). No subject had a treatment-related increase in liraglutide antibodies.
  
  About liraglutide
  
  Currently in phase 3 clinical trials, liraglutide is a human analogue of the naturally occurring hormone, Glucagon-Like Peptide-1 (GLP-1), which is rapidly broken down in the body and thus not practical as a therapy for type 2 diabetes. GLP-1 is released from the gastrointestinal tract upon ingestion of food. When glucose levels become too high, GLP-1 triggers the release of insulin from the pancreas and decreases the secretion of glucagon, a hormone that promotes glucose synthesis in the liver. GLP-1 releases insulin in a glucose-dependent manner, meaning that it only triggers insulin secretion if blood glucose is too high. This characteristic is thought to result in a low risk of hypoglycaemia, which has been confirmed in a number of studies in which GLP-1 was infused intravenously or subcutaneously.
  
  Novo Nordisk is a healthcare company and a world leader 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, Novo Nordisk has a leading position within areas such as haemostasis management, growth hormone therapy and hormone replacement therapy. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs more than 23,600 employees in 79 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 more information, visit novonordisk.com.

• 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).

• At its Capital Markets Day today, Novo Nordisk will report on solid progress in its pipeline of clinical development projects within diabetes care and biopharmaceuticals and confirm the positive outlook for the company's current key products.
  
  President and chief executive officer of Novo Nordisk, Lars Rebien Sørensen, said: "The steady progress in our development pipeline that we have seen during the past year, combined with today's announcement of three new clinical studies, provides Novo Nordisk with a good basis for delivering attractive growth rates in the future."
  
  Highlights from the day
  
  Announcement of initiation of three new clinical studies:
  
  - a phase 2 dose-ranging study for the use of liraglutide, the once-daily human GLP-1 analogue, as an anti-obesity agent for treatment of obese, non-diabetic people. The study is expected to be initiated during the first quarter of 2007;
  
  - a phase 3 study for the use of NovoSeven® in prophylactic treatment of haemophilia patients with inhibitors. The study is expected to be initiated during the first half of 2007, and
  
  - a phase 3 study for the use of Norditropin®, Novo Nordisk's liquid growth hormone, for treatment of adult patients in chronic dialysis. The study is expected to be initiated during 2007.
  
  Furthermore, Novo Nordisk will announce that it expects to file for regulatory approval of a heat-stable version of NovoSeven® around mid-2007.
  
  Insights into the research and development pipeline
  
  - Within diabetes care, insights will be provided into the company's activities to ensure a leadership position within next-generation modern insulin products, currently in phase 1 clinical trials. Furthermore, insights into the ongoing global liraglutide phase 3 programme and additional data from two completed liraglutide phase 2 studies.
  
  - Within haemostasis, insights into recent clinical results from phase 2 studies with NovoSeven® in prophylaxis, spinal surgery, traumatic brain injury and upper gastrointestinal (UGI) bleedings, respectively. Within treatment of UGI bleedings, NovoSeven® appeared to be safe with a comparable number of adverse events in placebo and NovoSeven® treated groups. There was no statistically significant difference in treatment success between placebo and NovoSeven® treated groups. As a consequence, Novo Nordisk will not pursue further clinical development activities with NovoSeven® within UGI bleedings. Finally, promising phase 1 results for the next-generation analogue of NovoSeven® will also be presented.
  
  Insights into the current business
  
  Within the Operations area, a review will be presented with primary focus on the rapidly growing North American and International Operations regions. The review confirms a solid growth outlook within diabetes care. This reflects both robust growth in the future number of new patients and the potential for increased penetration of Novo Nordisk's range of modern insulin products by further leveraging the company's market leadership position.
  
  Details of the significant improvements achieved within Product Supply with regard to increased production efficiency and the potential for further future improvements.
  
  Overview of Novo Nordisk's sustainable business model, including an update on how Novo Nordisk anticipates and manages global industry challenges such as access to health, business ethics and climate change.
  
  The above communication does not change Novo Nordisk's expectations for the financial results for 2006 as communicated on 2 August 2006 in connection with the announcement of financial results for the first six months of 2006.
  
  At 9.00 CET today, corresponding to 8.00 UK time, the Capital Markets Day will be webcast. A link to the live webcast will be available under the 'Investors' section of novonordisk.com. Presentation material for the webcast will be available on the same page.
  
  About treatment of obesity with liraglutide
  
  Obesity is an increasing global problem, which is associated with increased morbidity, including a significantly increased risk of developing type 2 diabetes. One of the main problems with existing obesity treatment is the sustainability of weight loss as many patients regain weight. Liraglutide, Novo Nordisk's once-daily human GLP-1 analogue, has shown the potential in both preclinical studies as well as in non-diabetic human subjects to reduce food intake and induce weight loss. The phase 2 study is expected to encompass more than 500 people.
  
  About prophylactic treatment with NovoSeven® in inhibitor patients
  
  NovoSeven® is approved for treatment of spontaneous bleeding events in haemophilia patients who have developed inhibitors to their current factor VIII or factor IX medication. In a recent phase 2 study, 22 patients were treated in a prophylactic manner, ie with one daily infusion of NovoSeven® during a three-month treatment period. Patients included in the study had experienced at least four bleeding episodes in the last month prior to inclusion in the study. The results show that daily prophylactic dosing of NovoSeven® significantly reduced the number of bleeding episodes during the treatment period, and the effects appeared to persist during a subsequent three-month observation period. No thrombo-embolic side effects were observed during treatment. The phase 3 study is in the planning phase, and is performed to allow subsequent filing for approval of prophylactic use of NovoSeven® in inhibitor patients.
  
  About treatment of Adult Patients in Chronic Dialysis (APCD)
  
  Patients in chronic dialysis treatment suffer from malnutrition as a consequence of the deterioration in their general metabolic status, and the annual mortality rate in APCD patients can be as high as 20%. In a recent phase 2 clinical study with 139 patients, Novo Nordisk has shown that administration of recombinant human growth hormone, Norditropin®, increases lean body mass and serum albumin - two important biomarkers of mortality and morbidity - in malnourished APCD patients, without giving rise to safety concerns. The phase 3 study is in the planning phase, will include more than 2,000 patients, and have mortality as the primary endpoint.
  
  Forward-looking statement
  
  The above sections contain forward-looking statements as the term is defined in the US Private Securities Litigation Reform Act of 1995. Forward-looking statements provide current expectations or forecasts of events such as new product introductions, product approvals and financial performance.
  
  Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations. Factors that may affect future results include interest rate and currency exchange rate fluctuations, delay or failure of development projects, production problems, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Novo Nordisk's products, introduction of competing products, Novo Nordisk's ability to successfully market both new and existing products, exposure to product liability and other lawsuits, proceedings and investigations, changes in reimbursement rules and governmental laws and related interpretation thereof, and unexpected growth in costs and expenses.
  
  Risks and uncertainties are further described in reports filed by Novo Nordisk with the US Securities and Exchange Commission (SEC) including the company's Form 20-F, which was filed on 6 February 2006. Please also refer to the section 'Risk Management' in the Annual Report 2005. Novo Nordisk is under no duty to update any of the forward-looking statements or to conform such statements to actual results, unless required by law.

Liraglutide phase 2 study shows increased insulin secretion and improved blood glucose control in people with type 2 diabetes

Liraglutide, an investigational treatment for type 2 diabetes, improved the ability of pancreatic beta cells to secrete insulin in people with type 2 diabetes, according to data presented today at the European Association for the Study of Diabetes (EASD) conference.[1]

The findings from the study, part of a larger, double-blind, placebo-controlled, randomised trial conducted over 14 weeks,[2] specifically showed that liraglutide increased the maximum capacity of beta cells to secrete insulin. In addition, first-phase insulin secretion, which is diminished in patients with type 2 diabetes, was increased.

The main trial showed that liraglutide reduced levels of HbA1c, the primary endpoint and a measure of a person’s average blood glucose level over the past two to three months. Additionally, participants on the highest dose of liraglutide lost significantly more weight than did those on placebo by the end of the 14-week study.

“We are excited by these results as they demonstrate that liraglutide monotherapy significantly improves blood glucose control without any risk of major or minor hypoglycaemia, is well tolerated, lowers body weight significantly and may help improve the body’s ability to produce insulin,” said study investigator Dr Tina Vilsboll, University Hospital Gentofte, Denmark.

“Diabetes treatment based on GLP-1 is an unusually interesting alternative to the existing treatment modalities,” said Professor Jens Juul Holst, Panum Institute. “However, the most exciting aspect is the possibility that GLP-1 treatment – especially because of its effects on beta cells – may halt the progression of disease that inevitably seems to accompany conventional treatment.”

Notes to editors - About the study

The larger study was a double-blind, placebo-controlled, randomised trial conducted over 14 weeks and included 165 patients with type 2 diabetes who were previously treated with diet or a single oral antidiabetic agent. Subjects on previous oral therapy had a four-week washout period. Patients were randomised to one of three once-daily doses of liraglutide (0.65 mg, 1.25 mg and 1.9 mg) or placebo.

Improved blood glucose control was achieved with liraglutide monotherapy. Levels of HbA1c, the primary endpoint, were significantly reduced compared to placebo in all liraglutide treatment groups (p<0.0001). at="at" dose,="dose," average="average" vs.="vs." 1.74%.="1.74%." between="between" 43="43" 50%="50%" who="who" received="received" 8%="8%" reached="reached" an="an" hba1c="hba1c" level="level" of="of" <7%. ="&lt;7%." improved="improved" glycaemic="glycaemic" control="control" was="was" achieved="achieved" no="no" major="major" or="or" minor="minor" hypoglycaemic="hypoglycaemic" episodes.="episodes." addition,="addition," patients="patients" liraglutide="liraglutide" had="had" a="a" reduction="reduction" in="in" bodyweight,="bodyweight," with="with" those="those" on="on" the="the" highest="highest" dose="dose" losing="losing" approximately="approximately" 3="3" baseline="baseline" and="and" 1.2="1.2" kg="kg" versus="versus" placebo="placebo" after="after" 14="14" weeks.="weeks." <br="&lt;br">
Liraglutide was well tolerated by participants in all groups, with the main adverse events being related to the gastrointestinal (GI) system. Nausea, which was experienced by 10% of participants in the high-dose group, and diarrhoea, were the most common adverse events; however, the frequency of all GI events declined over time.

An additional sub-study was performed as part of the 14 weeks’ study to assess parameters of beta-cell function. At baseline and after 14 weeks, these participants underwent standard tests to assess first-phase insulin secretion and maximal beta-cell insulin secretory capacity. Of 39 participants who began the study, 28 completed the 14 weeks of treatment. The two higher doses of liraglutide (1.25 mg and 1.9 mg) significantly increased beta-cell function compared to placebo by 114% and 97%, respectively (p<0.05 for="for" both="both" doses),="doses)," first-phase="first-phase" insulin="insulin" secretion="secretion" by="by" 124%="124%" and="and" 107%,="107%," respectively="respectively" (p<0.05). ="(p&lt;0.05)." <br="(p&lt;0.05).&lt;br">
Further findings from the study[3] showed that patients treated with liraglutide had improvements in markers for cardiovascular risk at all doses (0.65 mg, 1.25 mg, 1.90 mg). All doses showed a significant decrease in systolic blood pressure (liraglutide versus placebo = -5.21 to -7.91 mmHg, p<0.05), while="while" significant="significant" reductions="reductions" were="were" achieved="achieved" triglycerides="triglycerides" (liraglutide="(liraglutide" 0.65="0.65" pai-1="pai-1" blood="blood" clots);="clots);" and="and" bnp="bnp" (a="(a" marker="marker" for="for" of="of" or="or" vascular="vascular" disease);="disease);" 1.25="1.25" 1.90="1.90" mg="mg" versus="versus" placebo="-38%," p="0.01)." findings="findings" suggest="suggest" that,="that," well="well" as="as" its="its" direct="direct" diabetes="diabetes" control,="control," treatment="treatment" with="with" liraglutide="liraglutide" may="may" also="also" have="have" beneficial="beneficial" effects="effects" on="on" cardiac="cardiac" risk="risk" factors.="factors." longer-term="longer-term" studies="studies" are,="are," however,="however," needed="needed" to="to" confirm="confirm" these="these" effects.="effects." <br ="&lt;br">

About insulin

Pancreatic beta cells are responsible for producing insulin, a hormone that helps transport glucose from the bloodstream into body cells, providing them with an important source of energy and preventing blood glucose from becoming dangerously high. People with type 2 diabetes, the most common form of the condition, do not produce enough insulin or their body cells are less sensitive to it. While diet, exercise and weight loss may initially maintain control of blood glucose levels (glycaemic control), beta-cell function declines over time, requiring therapy with one or more oral antidiabetic (OAD) agents that boost insulin secretion or heighten insulin sensitivity. As beta-cell function further declines and OAD therapy eventually fails, insulin therapy is required.

One problem with insulin and some OAD therapies is that they can reduce blood glucose levels too far (hypoglycaemia), which can also be dangerous. Liraglutide acts to lower blood glucose only when levels become too high,[4],[5] and studies show it is associated with a low risk of hypoglycaemia.[6],[7] Furthermore, in animal models, liraglutide has been shown to decrease beta-cell apoptosis (programmed cell death) and increase beta-cell mass.[8],[9],[10],[11],[12]

About liraglutide

Currently in phase 3 clinical trials (LEAD), liraglutide is a long-acting analogue[13] of the naturally occurring hormone, glucagon-like peptide-1 (GLP-1), which is rapidly broken down in the body and thus not practical as a therapy for type 2 diabetes. GLP-1 is released from the gastrointestinal tract upon ingestion of food. When glucose levels become too high, GLP-1 triggers the release of insulin from the pancreas[14] and decreases the secretion of glucagon, [15] a hormone that promotes glucose synthesis in the liver. GLP-1 releases insulin in a glucose-dependent manner, meaning that it only triggers insulin secretion if blood glucose is too high. This characteristic results in a low risk of hypoglycaemia, which has been confirmed in a number of studies in which GLP-1 was infused intravenously or subcutaneously.[16],[17],[18],[19],[20],[21]

Studies to date show that liraglutide significantly improves glycaemic control in monotherapy and in combination therapy with metformin.[22],[23],[24],[25] Clinical trials have shown that liraglutide:

- Acts in a glucose-dependent manner, meaning that it stimulates insulin secretion and inhibits glucagon secretion only when blood glucose levels are higher than normal.[26],[27]
- Has a low risk of hypoglycaemia.[28], [29]
- Improves markers of beta-cell function.[30],[31]
- Is not associated with weight gain.[32]
- Is associated with mild to moderate and transient gastrointestinal side effects.[33],[34]
- Is suitable for once-daily administration.

[1] Vilsboell T, Brock B, Perrild H, et al. 14 weeks of liraglutide therapy in subjects with T2DM significantly improves 1st phase insulin secretion and maximal beta-cell secretory capacity. Late-breaking oral presentation (abstract 750195) at: 66th annual meeting of the American Diabetes Association, Washington, DC, 9–13 June 2006.

[2] Vilsboell T, Zdravkovic M, Le-Thi T, et al. Liraglutide significantly improves glycemic control, and lowers body weight without risk of either major or minor hypoglycemic episodes in subjects with type 2 diabetes. Oral presentation (abstract # 115-OR) at: 66th annual meeting of the American Diabetes Association, Washington, DC, 9–13 June 2006.

[3] Courrèges J-P et al. Liraglutide treatment, blood pressure and biomarkers of cardiovascular risk in patients with type 2 diabetes: 14 weeks monotherapy study. EASD 2006 (Oral presentation).

[4] Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004 May; 53(5):1187–94.

[5] Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, Galecki A, Halter JB. The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 2003; 52:1786–1791.

[6] Matthews S et al. A long-acting GLP-1 derivative, NN2211: its use in the treatment of type 2 diabetes. Poster 678. Presented at: European Association for the Study of Diabetes annual meeting, Budapest, Hungary, September 2002.

[7] Saad et al. The effect of NN2211, a long-acting GLP-1 derivative, on glycemic control and body weight in obese patients with Type 2 diabetes. Diabetologia 2002; 45(Suppl 2)A44. Presented at: European Association for the Study of Diabetes annual meeting, Budapest, Hungary, September 2002.

[8] Sturis J, Gotfredsen CF, Rømer J, Rolin B, Ribel U, Brand CL, et al. GLP-1 derivative liraglutide in rats with beta-cell deficiencies influence of metabolic state on beta-cell mass dynamics. Br J Pharmacol 2003; 140:123–132.

[9] Rolin B, Larsen MO, Gotfredsen CF, Deacon CF, Carr RD, Wilken M, Knudsen LB. The long-acting GLP-1 derivative, NN2211, ameliorates glycemia and increases ß-cell mass in diabetic mice. Am J Physiol Endocrin Metab 2002; 283:E745–E752.

[10] Bregenholt S et al. The GLP-1 analogue, NN2211, inhibits free fatty acid-induced apoptosis in primary rat b-cells. Diabetologia 2001; 44(S1):A19.

[11] Bregenholt S et al. The GLP-1 derivative NN2211 inhibits cytokine-induced apoptosis in primary rat b-cells. Diabetes 2001; 50(S2):A31.

[12] Bregenholt S, Moldrup A, Blume N, Karlsen AE, Nissen Friedrichsen B, Tornhave D, Knudsen LB, Petersen JS. The long-acting glucagon-like peptide-1 analogue, liraglutide, inhibits beta-cell apoptosis in vitro. Biochem Biophys Res Commun 2005 May 6; 330(2):577–84.

[13] Knudsen LB, et al. GLP-1 derivatives as novel compounds for the treatment of type 2 diabetes: selection of NN2211 for clinical development. Drugs of the Future 2001; 26(7):677–685.

[14] Vilsbøll et al. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 2002; 45:1111–1119.

[15] Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004 May; 53(5):1187–94.

[16] Rachman J et al. Near-normalisation of diurnal glucose concentrations by continuous administration of glucagon-like peptide-1 (GLP-1) in subjects with NIDDM. Diabetologia 1997 Feb; 40(2):205–11.

[17] Toft-Nielsen MB et al. Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes. J Clin Endocrinol Metab 2001 Aug; 86(8):3853–60.

[18] Zander M et al. Additive effects of glucagon-like peptide 1 and pioglitazone in patients with type 2 diabetes. Diabetes Care 2004 Aug; 27(8):1910–4.

[19] Zander M et al. Effect of 6-week course of glucagon-like peptide 1 on glycemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002 Mar 9; 359(9309):824–30.

[20] Zander M et al. Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes. Diabetes Care 2001 Apr; 24(4):720–5.

[21] Meneilly GS et al. Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care 2003 Oct; 26(10):2835–41.

[22] Feinglos MN, Saad MF, Pi-Sunyer FX, An B, Santiago O; Liraglutide Dose-Response Study Group. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycemic control and bodyweight in subjects with Type 2 diabetes. Diabet Med 2005 Aug; 22(8):1016–23.

[23] Harder H, Nielsen L, Tu DT, Astrup A. The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes. Diabetes Care 2004 Aug; 27(8):1915–21.

[24] Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR; NN2211-1310 International Study Group. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analogue liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care 2004 Jun; 27(6):1335–42.

[25] Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004 May; 53(5):1187–94.

[26] Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004 May; 53(5):1187–94.

[27] Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, Galecki A, Halter JB. The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 2003; 52:1786–1791.

[28] Matthews S et al. A long-acting GLP-1 derivative, NN2211: its use in the treatment of type 2 diabetes. Poster 678. Presented at: European Association for the Study of Diabetes annual meeting, Budapest, Hungary, September 2002.

[29] Saad et al. The effect of NN2211, a long-acting GLP-1 derivative, on glycemic control and body weight in obese patients with Type 2 diabetes. Diabetologia 2002; 45(Suppl 2)A44. Presented at: European Association for the Study of Diabetes annual meeting, Budapest, Hungary, September 2002.

[30] Degn KB, Juhl CB, Sturis J, Jakobsen G, Brock B, Chandramouli V, Rungby J, Landau BR, Schmitz O. One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004 May; 53(5):1187–94.

[31] Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, Galecki A, Halter JB. The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 2003; 52:1786–1791.

[32] Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR; NN2211-1310 International Study Group. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analogue liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care 2004 Jun; 27(6):1335–42.

[33] Ibid

[34] Feinglos MN, Saad MF, Pi-Sunyer FX, An B, Santiago O; Liraglutide Dose-Response Study Group. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycemic control and bodyweight in subjects with Type 2 diabetes. Diabetes Med 2005 Aug; 22(8):1016–23.

28 April 2006
Financial statement for the period 1 January 2006 to 31 March 2006

• Novo Nordisk increased sales by 23% in the first quarter of 2006Novo Nordisk increased sales by 23% in the first quarter of 2006 Sales increased by 23%, positively impacted by the development in foreign currencies (sales growth in local currencies of 18%)
  
  - Sales of insulin analogues increased by 60%
  - Sales of NovoSeven® increased by 16%
  - Sales in North America increased by 32%
  - Sales in International Operations increased by 56%
  
  Operating profit increased by 24% to DKK 1,880 million. Adjusted for the impact from currencies, underlying operating profit increased by around 12%.
  
  Net profit decreased by 2% to DKK 1,211 million. Adjusted for non-recurring gains in the first quarter of 2005, net profit increased by more than 15%. Earnings per share (diluted) increased by 1% to DKK 3.72.
  
  Novo Nordisk expects to report Danish kroner sales growth in 2006 of 11-13%, while operating profit is still expected to grow by slightly more than 10%.
  
  The phase 3 programme for liraglutide, the once-daily human GLP-1 analogue, including around 3,800 type 2 diabetes patients was initiated in February 2006.
  
  Lars Rebien Sørensen, president and CEO, said: "Novo Nordisk had a strong first quarter of 2006 with continuing sales growth globally. We expect 11-13% sales growth for the full year supported by the recent launch of Levemir® in the US, where Novo Nordisk is now the only company with a full portfolio of insulin analogues."

• Providing glucose control and weight loss without hypoglycaemia
  
  Novo Nordisk today announced clinical results from its phase 2b study of the safety and efficacy of liraglutide, the once-daily, fully-human GLP-1 analogue. The study, which was a double-blind, placebo-controlled, randomised, monotherapy study over 14 weeks, included 165 patients with type 2 diabetes that were previously treated with diet or oral antidiabetic agents.
  
  An improvement of haemoglobinA1c (HbA1c) of between 1.5 and 2 percentage points was achieved by treatment with liraglutide compared to placebo. At the highest dose more than 45% of patients achieved a target of HbA1c equal to or below 7% compared to less than 8% treated with placebo. An HbA1c level below 7% is recommended by the American Diabetes Association. The average HbA1c level at the beginning of the study was just below 8.5%.
  
  At the highest liraglutide dose the improvement in fasting plasma glucose achieved was above 3 mM (> 54 mg/dl). In addition, these patients reduced their bodyweight by approximately 3 kg from a baseline of around 90 kg.
  
  Liraglutide was well tolerated and nausea was reported at a level of 5-10%. Gastrointestinal side effects occurred most frequently in the beginning of the study, whereafter the frequency decreased substantially. There were no cases of major or minor hypoglycaemia in spite of the significant improvement in glycaemic control.
  
  Mads Krogsgaard Thomsen, chief science officer and executive vice president of Novo Nordisk, said: "The impressive clinical data for liraglutide holds great promise for improving the treatment of type 2 diabetes; simultaneous glucose control and weight loss in the absence of hypoglycaemic events."
  
  Novo Nordisk expects to communicate full results from the phase 2b study at a scientific meeting in 2006. As previously communicated, phase 3 studies with liraglutide including approximately 3,800 patients are expected to start in February 2006.

• Tomorrow Novo Nordisk will break ground for a new facility in Kalundborg, Denmark. The plant will produce liraglutide, a potential new Novo Nordisk product for treating type 2 diabetes.
  
  The new facility is scheduled for completion in 2005 and will create about 100 new jobs in Kalundborg. About 7,000 square metres in size, the plant represents an investment of about 800 million Danish kroner.
  
  It is only a year since Novo Nordisk inaugurated the world’s largest insulin facility in Kalundborg and started building an insulin purification plant. Once the new facility is in operation, Novo Nordisk will employ about 2,200 people in the Kalundborg area.
  
  Liraglutide is a derivative of glucagon-like peptide 1 (GLP-1), a natural human hormone, and represents a new principle in the treatment of type 2 diabetes. Studies have shown that the new product lowers blood glucose with little or no risk of inducing hypoglycaemia (low blood glucose). It is also expected to affect appetite regulation leading to weight management. Liraglutide may also be able to regenerate insulin-producing cells (beta cells).
  
  The product has completed clinical phase 2, and phase 3 trials are expected to be initiated in the second half of this year.

• Solid first quarter – growth in net profit for 2003 still expected to approach 10%
  
  Sales in local currencies increased by 24% compared to the first quarter of 2002. Measured in Danish kroner, sales increased by 11% to DKK 6,106 million. The performance in local currencies per therapy area was as follows:
  
  - Diabetes care sales increased by 24%.
  - Haemostasis management (NovoSeven®) sales increased by 32%.
  - Growth hormone therapy sales increased by 27%.
  - Hormone replacement therapy decreased by 14%.
  
  Operating profit increased by 6% to DKK 1,320 million in the first quarter of 2003. Adjusted for non-recurring items in the first quarter of 2002 operating profit increased by more than 15% despite the challenges caused by the strengthening of the Danish krone.
  
  Net profit increased by 32% to DKK 1,091 million as a result of the growth in operating profit and net financial income of DKK 333 million in the first quarter of 2003 related to significant currency hedging gains.
  
  Reflecting the impact from the continued strengthening of the Danish krone, Novo Nordisk now expects operating profit to grow by a low single-digit percentage rate in 2003, whereas income from hedging of currency exposure will now increase expected net financial income to DKK 700 million. Net profit growth is consequently still expected to approach 10%.
  
  Lars Rebien Sørensen, president & CEO, said, ”The solid underlying performance in the first quarter enables us to maintain our net profit expectations for the full year, despite the challenging business environment in 2003.”
  
  Liraglutide (NN2211), the once daily human GLP-1 analogue has completed the final dose optimisation phase 2 trials with positive results.

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