Data presented at the Diabetes UK Annual Professional Congress in Glasgow show that the, human GLP-1 analogue, liraglutide is effective at reducing HbA1c in patients with type 2 diabetes and also significantly reduces body weight in study participants with type 2 diabetes compared to placebo 1, 2, 3. Novo Nordisk has made a marketing authorisation application to the European Medicines Agency (EMEA) in Europe.

The data analysis from the LEAD 2 and LEAD 5 phase III, 26-week studies, part of the LEAD™ (Liraglutide Effect and Action in Diabetes) study programme evaluated the effect of once daily liraglutide, an incretin-based therapy, when combined with various oral antidiabetic therapies.

Key clinical findings presented at the congress:

Liraglutide reduces HbA1c1

Data analysis from the LEAD 2 and LEAD 5 studies examined the impact of baseline HbA1c on response to liraglutide. The results showed that treatment with liraglutide 1.8mg/day resulted in clinically meaningful reductions in HbA1c irrespective of baseline HbA1c levels and reductions increased with higher baseline HbA1c levels.

Liraglutide reduces body weight2

Data analysis from the LEAD 2 and LEAD 5 studies explored the impact of baseline BMI on response to liraglutide 1.8mg when combined with commonly used oral antidiabetic therapies. Results from both studies found that study participants in all BMI subgroups experienced weight loss with liraglutide. The greatest decrease in body weight occurred in study participants with BMI ≥ 35kg/m2 (-4.4kg). In both studies, the control regimens (glimepiride + metformin in LEAD 2 and insulin glargine + glimepiride + metformin in LEAD 5) were associated with increases in body weight in all BMI subgroups, ranging from 0.4 to 2.2 kg.

Liraglutide reduces systolic blood pressure3

Type 2 Diabetes is associated with increased blood pressure and therefore cardiovascular disease. A decrease in 5.6mmHg systolic blood pressure will decrease the risk of death from cardiovascular disease by 18% in this group of patients. 9

Data analysis from LEAD 2 and LEAD 5 explored the impact of Liraglutide on blood pressure. Results from both studies show a decrease in blood pressure with Liraglutide. The greatest reduction occurred in LEAD 5 which demonstrated a mean decrease in systolic blood pressure of 4mmHg with Liraglutide 1.8mg.

Liraglutide reduces visceral fat rather than lean tissue4

A sub-group analysis of study participants in LEAD 2 investigated the effect of liraglutide on body composition. At 26 weeks there was a statistically significantly greater reduction in central-body visceral fat with liraglutide (liraglutide + metformin, 13-17% reduction from baseline) compared to the control group (glimepiride + metformin, 4.8% reduction). A statistically significant greater reduction in central-body subcutaneous adipose tissue was also observed with liraglutide compared to the control group.

Liraglutide and patient-reported outcomes5

Patient reported outcomes were examined in a subgroup of patients from the LEAD 2 trial, comparing subjects with Type 2 diabetes treated with once-daily liraglutide or glimepiride, both as add-on to metformin. Treatment satisfaction was assessed with the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the impact of weight on quality of life was assessed using the Impact of Weight on Quality of Life Questionnaire - Lite version (IWQOL-Lite).

The results showed that there were no significant differences in overall treatment satisfaction between groups. In addition Liraglutide was associated with improvements in perceived frequency of hypo and hyperglycaemia and public distress with respect to weight compared with glimepiride.

About the studies

The data presented today are from the LEAD 2 and LEAD 5 studies which form part of the LEAD™ (Liraglutide Effect and Action in Diabetes) program for liraglutide. The LEAD™ programme consists of five (four 26-week and one 52-week) randomised, controlled, double-blinded phase IIIa studies, involving more than 4,000 study participants with type 2 diabetes in 40 countries.

LEAD 2 - a placebo-controlled, 26 week double-blind, randomised study compared the efficacy of liraglutide (0.6, 1.2 or 1.8mg/day) + metformin (1g BID) vs. metformin monotherapy (1g BID) vs. metformin + glimepiride (4mg/day) on glycaemic control in study participants with type 2 diabetes. The trial included 1091 subjects with a mean body weight of 88.6kg and HbA1c level of 8.4. 35% of study participants were previously treated with OAD monotherapy and 65% treated with combination therapy.

LEAD 5 - a 26-week randomised trial compared the efficacy and safety of liraglutide (1.8mg OD) + metformin (1mg BID) + glimepiride (2-4mg OD) vs. placebo + metformin (1mg BID) + glimepiride (2-4mg OD) vs. insulin glargine + metformin (1mg BID) + glimepiride (2-4mg OD). The trial included 581 study participants with a mean age of 57.5, a mean body mass index of 30.5kg/m2 and mean HbA1c of 8.2%. 6% of study participants were previously treated with monotherapy and 94% of study participants were on combination therapy.

About liraglutide

The human GLP-1 analogue liraglutide has been developed for once daily treatment of type 2 diabetes. Liraglutide works by stimulating the release of insulin only when glucose levels become too high and by inhibiting appetite. Liraglutide when given once daily has additional benefits of very low levels of hypoglycaemia. Novo Nordisk submitted a marketing authorisation application to the European Medicines Agency (EMEA) in Europe, for the approval of liraglutide for the treatment of study participants 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 study participants, 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'.

References

1. Russell-Jones D. The once-daily human GLP-1 analogue liraglutide substantially reduces HbA1c in subjects with Type 2 diabetes, irrespective of HbA1c at baseline. Annual Professional Conference, Diabetes UK. 11-13 March 2009. (Poster no. 361)

2. Russell-Jones, D. The once-daily human GLP-1 analogue liraglutide reduces body weight in subjects with Type 2 diabetes, irrespective of body mass index at baseline. Annual Professional Conference, Diabetes UK. 11-13 March 2009. (Poster no. 419)

3. Matthews D. Liraglutide, a once-daily human glucagon-like peptide-1 analogue, reduces systolic blood pressure in subjects with Type 2 diabetes. Annual Professional Conference, Diabetes UK. 11-13 March 2009. (Poster no. 305)

4. Matthews, D. Liraglutide, a once-daily human GLP-1 analogue, reduces fat percentage and visceral and subcutaneous adipose tissue compared with glimepiride when added to metformin in subjects with Type 2 diabetes. Annual Professional Conference, Diabetes UK. 11-13 March 2009. (Poster no. 130)

5. Vel S Evaluation of patient-reported outcomes in subjects with Type 2 diabetes treated with once-daily human GLP-1 analogue liraglutide or glimepiride, both as add-on to metformin. Annual Professional Conference, Diabetes UK. 11-13 March 2009. (Poster no. 362)

6. UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 854-65.

7. Obesity Factsheet No. 311. World Health Organization website. Accessed 2 July 2008

8. Inzucchi, SE. JAMA 2002; 287: 360-72

9. Patel A et al. Lancet 2007; 370:829-40

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