Diabetes is a metabolic condition that leads to high blood sugar levels, which can have serious consequences for short- and long-term health. People with diabetes experience raised blood sugar because of a partial or complete reduction of insulin production in their bodies. Most people with diabetes (85–95%) [1] have type 2 diabetes, in which the pancreas produces insufficient quantities of insulin and/or insulin has a reduced effect on the muscle and liver cells.

The disorder is a result of a combination of genetic susceptibility and external environmental factors. The beta cells in the pancreas are unable to produce an adequate surge of insulin after a meal, which normally allows the body to convert excess glucose into glycogen and maintain blood sugar at a constant level. Therefore, blood glucose levels rise.

Victoza, which has 97% homology to natural human GLP-1 peptide [2], could help patients maintain normal blood sugar levels with a once-daily injection that can be taken at any time of day, irrespective of meals. Victoza works with the body to lower glucose levels by stimulating the release of insulin only when glucose levels become too high [2]. The benefit to the patient is that there is a reduced risk of hypoglycaemia (blood sugar becoming too low).

Furthermore, Victoza can help patients achieve weight loss, by increasing satiety and delaying gastric empting and, thus, reducing caloric intake [2]. This is an important factor in treating patients with type 2 diabetes because many patients are overweight [3], and weight gain is a side-effect of some common treatment regimens for type 2 diabetes, increasing the risk of obesity-related illnesses [4–6].

Studies have also shown that two additional potential benefits of Victoza are a reduction in systolic blood pressure [2] and improved beta-cell function, enabling increased insulin secretion [7]. These findings have been consistently demonstrated throughout the Phase III liraglutide effect and action in diabetes (LEAD)TM trials [2,7–9].

LEADTM, an extensive clinical development programme, involved approximately 2500 patients with type 2 diabetes receiving Victoza in 40 countries. The programme included five randomized, controlled, double-blind Phase III studies investigating the use of liraglutide with three widely used classes of antidiabetic drugs – sulphonylurea, glitazone and metformin [2,7,8,10].

The results of the LEAD™ 6 study [11], a direct comparison between Victoza and exenatide (both GLP-1 receptor agonists), showed that patients treated with Victoza had a drop in HbA1c of 1.12%, compared with a drop of 0.79% in the group that received exenatide. Victoza was also significantly better than exenatide at lowering fasting plasma glucose (–1.61 mmol/L vs –0.60 mmol/L) [11]. Both treatments led to a weight reduction of approximately 3 kg during the 26-week study [11].

References

1 Diabetes in the UK 2004, Diabetes UK. http://www.diabetes.org.uk/Documents/Reports/in_the_UK_2004.doc. Accessed June 2009
2 Zinman, B. et al. Efficacy and safety of the human GLP-1 analog liraglutide in combination with metformin and TZD in patients with type 2 diabetes mellitus (LEAD-4 Met+TZD). Diabetes Care (in press)
3 British Nutrition Foundation (2004) Diabetes. http://www.nutrition.org.uk/printArticle.asp?dataId=1377
4 Triplitt, C. et al. (2007) The changing landscape of type 2 diabetes: the role of incretin-based therapies in managed care outcomes. J. Manag. Care Pharm. 13 (Suppl. C), S2–S16
5 Krentz, A.J. (2008) Management of type 2 diabetes in the obese patient: current concerns and emerging therapies. Curr. Med. Res. Opin. 24, 401–417
6 Leslie, W.S. et al. (2007) Weight gain as an adverse effect of some commonly used prescribed drugs: a systematic review. QJ 100, 395–404.
7 Nauck, M. et al. for the LEAD-2 Study Group (2009) Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 32, 84–90
8 Marre, M. et al. (2009) Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone in patients with type 2 diabetes. Diabet. Med. 26, 268–278
9 Matthews, D.R. et al. Poster 892. Presented at 44th Annual Meeting of the EASD, Rome, Italy, September 2008
10 Russell-Jones, D. et al. (2008). Significantly better glycemic control and weight reduction with liraglutide, a once-daily human GLP-1 analog, compared with insulin glargine: all as add-on to metformin and a sulfonylurea in type 2 diabetes. American Diabetes Association meeting, San Francisco, 6–10 June. Abstract 536-P
11 Buse, J. et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet (in press) 10.1016/S0140-6736(09)60659-0