The first once-daily human glucagon-like peptide 1 (GLP-1) analogue, liraglutide (Victoza) for the treatment of type 2 diabetes mellitus (T2DM) has been launched in the UK.
Described by the manufacturer, Novo Nordisk as “a revolutionary product”, liraglutide works in a unique way – only when glucose levels become too high – to stimulate insulin release and suppress glucagon secretion. A member of the ‘incretin’ drug family, the drug is administered subcutaneously once-daily in adults with T2DM who do not achieve glycaemic control, in combination with metformin or a sulphonylurea (SA), or a combination of metformin and a sulphonylurea, or metformin and a thiazolidinedione (glitazone).
Incretin-based therapies are a relatively recent innovation. Incretins are produced in the gastrointestinal tract and are secreted in response to a meal. GLP-1 is the most powerful, naturally occurring incretin, which increases insulin secretion in the beta cells of the pancreas. Naturally occurring incretin is limited by its half-life as it is rapidly degraded, whereas liraglutide, an almost identical analogue of human GLP-1 (97% homology), allows for 24-hour effects with once-daily administration.
Liraglutide appears to facilitate normalisation of glucose as well as cause deceleration of gastric emptying, and appetite suppression/weight loss.
An extensive clinical development programme, LEAD (Liraglutide Effect and Action in Diabetes), involving some 2,500 patients, has shown that the drug substantially lowered fasting and postprandial glucose concentrations, with an overall reduction in glycosylated haemoglobin (HbA1c) of up to 1-2%, and it was associated with weight loss and reduction in systolic blood pressure of about 7 mmHg.
Speaking at the launch meeting, Professor Anthony Barnett (Professor of Medicine and Honorary Consultant Physician, Heart of England NHS Trust, Birmingham) said that liraglutide, works so well, “and ticks so many boxes” that it was “almost too good to be true”.
He emphasised the need for early treatment of T2DM to prevent later complications. “Control matters,” he said, adding that patients taking liraglutide can be “confident they are controlling their blood sugar, and they may benefit from weight loss”. There was the added advantage that, because of its mode of action, there was minimal risk of hypoglycaemia (‘hypos’) and that, additionally, “the once-daily formula, independent of meals, should improve patient compliance and, in turn, clinical outcomes”.
Further clinical trials may determine whether liraglutide will have an effect on diabetes progression and have positive effects in reducing cardiovascular risk, in Professor Barnett’s view.
Liraglutide will have a National Institute for Health and Clinical Excellence (NICE) Technology Appraisal next year. Professor Barnett said he thought that it would be “incredibly disappointing” if PCTs were to restrict its use and not have the drug widely prescribed before this time. He hopes the fact that the drug is injectable (via a very fine needle, causing minimal discomfort) will not concern patients. It will be a “big step” to get patients to try it but he believes this will be worthwhile.
Manchester general practitioner, Dr Chris Steele, called for a national screening campaign at the launch meeting, pointing out there are still up to one million people with undiagnosed diabetes in the UK. The condition results in enormous costs, close to £10 million a day, in treating diabetes and its complications.
Dr Steele also said that he believed that the introduction of liraglutide may well “change the lives of many diabetic patients” for the better.