New Data From A Phase 3 Study Confirms Clinical Benefits Of Once-Daily Liraglutide In The Management Of Type 2 Diabetes

Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials
Article Date: 08 Sep 2008 - 4:00 PDT

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Data from a phase 3 clinical study (LEAD™ 4) presented at the 44th Annual Meeting of the European Association for the Study of Diabetes (EASD) demonstrated that adding the investigational new drug liraglutide, a human GLP-1 analogue, to metformin and rosiglitazone in the treatment of type 2 diabetes, leads to improved blood glucose lowering (HbA1c)1, weight loss, blood pressure reduction and improvement in beta cell functioning.

Participants in the study were randomised 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 percentage points 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 (ADA) HbA1c target of <7.0%2 compared to 28% of those who received placebo (p<0.0001). Likewise, more than 35% of the patients in the liraglutide groups reached HbA1c ≤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 (p<0.01).1

In addition to improved glucose lowering, liraglutide treatment also led to significant weight loss. Mean body weight decreased significantly for liraglutide compared to an overall weight increase in the metformin and rosiglitazone group, leading to an absolute weight difference of up to 2.6 kg less in the liraglutide patients compared to placebo (p<0.0001).1 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™ 4 also led to a statistically significant decrease in blood pressure as seen in three of the other LEAD™ studies: reductions of 6.7 mmHg and 5.6 mmHg with liraglutide 1.2 mg and 1.8 mg, respectively, were observed compared to a decrease of 1.1 mmHg in the comparator group (p<0.001).1

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.1 Beta cell function is an important measure of disease progression in type 2 diabetes.

LEAD™ 4 is the last of the five phase 3a LEAD™ (Liraglutide Efficacy and Action in Diabetes) studies to be presented.

"The complete LEAD™ programme provides convincing evidence that liraglutide represents an effective new treatment approach for type 2 diabetes," said Dr Zinman, professor of Faculty of Medicine, University of Toronto and director of the Diabetes Centre Mount Sinai Hospital, Toronto, Canada. "Liraglutide offers effective glucose lowering as monotherapy or as an add-on to other oral diabetes therapies while also consistently lowering weight and blood pressure and enhancing beta cell function."

About the study

The LEAD™ 4 study was a 26-week randomised 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 randomised to liraglutide or placebo.

Safety and tolerability of liraglutide

There were no major hypoglycaemic episodes reported during the study. The rate of minor hypoglycaemia (<3.1 mmol/L) was low in all groups (0.38, 0.64 and 0.17 events/subject year with liraglutide 1.2 mg, 1.8 mg and placebo, respectively). Nausea was the most common adverse event and was reported more frequently in the liraglutide patients: 29% and 40% in the 1.2 mg and 1.8 mg groups respectively, compared to 9% in the placebo group. Nausea associated with liraglutide treatment occurred early in the treatment regimen, was well tolerated and returned to the placebo levels after the first 16 weeks of the study.1

About liraglutide

Once-daily liraglutide is the first human Glucagon-Like Peptide-1 (GLP-1) analogue 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 23 May 2008, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration in the US as well as a marketing authorisation 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 15 July 2008.

About LEAD™ (Liraglutide Effect and Action in Diabetes)

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

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'.

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