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New GLP-1 agonist claims price advantage

Glucagon-like peptide-1 (GLP-1) receptor agonists have proved to be a useful addition to the diabetologist’s toolkit.

Who it is for

Glucagon-like peptide-1 (GLP-1) receptor agonists have proved to be a useful addition to the diabetologist’s toolkit. Medicines that can generate weight loss and that tend not to cause hypoglycaemia have obvious advantages for patients with type 2 diabetes. Both exenatide (prolonged release) and liraglutide are recommended by the National Institute for Health and Care Excellence as third-line options for diabetes treatment in those who:

  • Are overweight (body mass index >35kg/m2), or
  • Would benefit from losing weight to aid other weight-related problems, or
  • Would struggle to continue working if they were prescribed insulin

No doubt the restriction placed on the drugs’ use is due, in part, to their cost (compared with other third-line treatment options).

Now a third GLP-1 receptor agonist, lixisenatide (Lyxumia; Sanofi), is available. And, according to the marketing material, the strategy is clear: “Turn to the GLP-1 that minimises cost.” Will clinicians and formulary committees be convinced of its worth?

How it works

Drugs in the GLP-1 family act through several mechanisms. “In diabetic patients, glucagon levels tend to be slightly raised,” explains Clifford Bailey, professor of clinical science and head of diabetes research at Aston University. “GLP-1 receptor agonists suppress glucagon — a hormone that causes the liver to secrete glucose into the bloodstream. This suppression means less insulin is required to control glucose levels after meals. The drugs also enhance insulin secretion.”

In addition, GLP-1 receptor agonists slow gastric emptying, meaning dietary glucose does not enter the bloodstream as quickly. This tends to cause nausea in many patients but may also reduce appetite, both of which could be mechanisms for weight loss.


Lixisenatide has been compared with placebo in several arms of the industry-sponsored GETGOAL study. In one arm, 446 patients whose diabetes was inadequately controlled with insulin glargine (with or without a sulfonylurea) were randomised to receive lixisenatide or placebo.1 Change in HbA1c was measured 24 weeks after randomisation. Lixisenatide reduced HbA1c by 0.71 per cent, compared with 0.40 per cent for placebo (P<0.0001). Symptomatic hypoglycaemia was more common in the treatment group.

In a second arm, 680 patients whose diabetes was inadequately controlled with metformin were randomised to receive lixisenatide or placebo in the morning or evening.2 Lixisenatide reduced HbA1c by 0.9 per cent in the morning, and 0.8 per cent in the evening, compared with 0.4 per cent for placebo (both times). The difference was statistically significant in both the morning and evening (P<0.0001). Symptomatic hypoglycaemia was again more common in the treatment group.

In a third arm, lixisenatide and placebo were compared in 361 patients who were not on any other diabetes treatment.3 The treatment regimen involved either a one-step (10µg daily for two weeks then 20µg) or a two-step (10µg daily for one week, 15µg for one week then 20µg) increase. After 12 weeks, HbA1c had reduced by 0.94 per cent in the one-step group and by 0.77 per cent for the two-step group. This compared with a 0.27 per cent reduction for the placebo groups combined (P<0.0001).

“Not all trials have been published and, of those that have, one of the biggest was conducted in Asia,” says Victoria Ruszala, lead pharmacist for diabetes at North Bristol NHS Trust. “It would be fair to say there are gaps in the evidence. Plus, the evidence so far has only confirmed that lixisenatide is equivalent to existing therapy, not better,” she adds.


As for other GLP-1 receptor agonists, lixisenatide is administered by subcutaneous injection into the thigh, abdomen or upper arm, using a prefilled pen and pen needles.

The dose starts at 10µg daily, and increases to 20µg daily after 14 days. It should be given in the hour before the first meal of the day or the evening meal. “If timed correctly,” says Professor Bailey, “it can control the postprandial hyperglycaemia that occurs after the main meal of the day.”

Mrs Ruszala points out: “Trials did suggest that lixisenatide led to fewer postprandial glucose spikes. However, this effect has been shown with the other GLP-1 receptor agonists and is likely related to the pharmacology of the class, rather than lixisenatide specifically.”

By comparison, exenatide is available as a twice-daily or once-weekly formulation. Liraglutide is also administered once a day, but can be administered at any time because it acts for 24 hours. Lixisenatide does not quite provide 24-hour cover, but Professor Bailey thinks this might, in some patients, be advantageous: “You may not want to stimulate a receptor all of the time — this could potentially lead to reduced responsiveness.”

Patients will usually be shown how to use the pen by their GP or diabetes nurse but useful points for pharmacists to note include that the pen device must be activated before first use and there is a coloured indicator window to check this has been done. If a dose is missed, it should be injected within the hour before the next meal.

The pens should be stored in a refrigerator but once in use can be kept below 30C.


Nausea, vomiting, diarrhoea and headache are all listed as “very common” side effects in Lyxumia’s summary of product characteristics. “Lixisenatide has fewer gastrointestinal side effects than exenatide, but then so does liraglutide,” Mrs Ruszala points out. “Without a trial that compares lixisenatide with liraglutide there is no evidence to suggest one is better [in terms of these side effects] than the other.”

Hypoglycaemia does seem to occur when lixisenatide is used with a sulfonylurea, insulin or, to a lesser extent, metformin. If used in combination therapy with a sulfonylurea or a basal insulin, blood glucose monitoring may be needed to adjust the doses of the sulfonylurea or the insulin.

Other potential side effects include upper respiratory tract infections, cystitis, dizziness, back pain and injection-site reactions.

The SPC recommends that patients should be educated about characteristic symptoms of acute pancreatitis (ie, persistent, severe abdominal pain).

Lyxumia is not recommended in women of childbearing age and not using contraception.


Lixisenatide costs £54.14 for 28 days’ treatment — consisting of two pens. A 28-day supply of exenatide (10µg bd) costs £68.24 (for the modified release preparation, this increases to £73.76), while a 30-day supply of liraglutide (1.2mg od) costs £78.48. “The cost of lixisenatide is lower,” says Mrs Ruszala, “but you would have to switch all patients who are currently on a GLP-1 receptor agonist to generate any considerable saving. If this was the case, the clinicians would be switching from using a drug they know well to a drug they know very little about — not many will want to do that.”

Place in therapy

Despite lixisenatide being, essentially, a “me too” drug, Professor Bailey can see potential benefits in making a third GLP-1 receptor agonist available. “If you suffer particularly from nausea, exenatide modified release taken before bed might be the most appropriate. If you have a variable lifestyle, liraglutide may be more suited. If you have one main meal a day, lixisenatide could be better for you,” he said. He thinks that Lyxumia’s lower cost will endear it to formulary committees. And where there is reticence, he adds: “It can be a false economy to be too restrictive. Putting patients on insulin is very expensive and has a massive impact on their life. Any intervention that can prevent patients from being put on insulin unnecessarily should be available.”

Mrs Ruszala, on the other hand, is less positive: “I can’t see it adding much to the existing GLP-1 receptor agonist offering. It doesn’t offer a big advantage over current therapies.”

An issue Professor Bailey does have with GLP-1 receptor agonists is their unpredictable effect. “We are not yet able to determine in advance which patients will respond to GLP-1 receptor agonists,” he says. “Some achieve glycaemic control, some achieve weight control, some gain control of both while others derive only marginal benefit. At present, we cannot predict.” 

Key points

  • Lixisenatide (Lyxumia) is a glucagon-like peptide-1 receptor agonist that is a cheaper alernative to the three other GLP-1 agonist products currently available.
  • There is little evidence that lixisenatide is better than existing GLP-1 agonist products.
  • Like other GLP-1 agonists, weight loss may be a benefit.
  • Lixisenatide requires once a day injection via a pen device prefilled with 14 doses. It should be given in the hour before a meal.

 Gareth Malson is a pharmacist and freelance writer.


Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2013.11122965

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