Lixisenatide

Origin and structure

Lixisenatide is a synthetic peptide of 44 amino acids built on exendin-4, a peptide from the Gila monster (Heloderma suspectum) that activates the human GLP-1 receptor and, made synthetically, is the medicine exenatide. Compared with exendin-4, one proline near the end of the chain has been removed and six lysines have been added, and the last amino acid carries an amide. Its molecular formula is C215H347N61O65S and its molecular weight 4,858.5 daltons. The active substance is made by solid-phase chemical synthesis.

Lixisenatide comes from the Danish company Zealand Pharma, which held the patent family on it and in 2003 gave Sanofi an exclusive worldwide licence to develop and sell it. Zealand describes its SIP technology as adding a short run of amino acids that tightens a peptide's structure and makes it harder to break down, and names lixisenatide as one of the peptides developed with it. In research the compound has also been known as ZP10 and AVE0010.

Unlike liraglutide and semaglutide, lixisenatide carries no fatty-acid chain. It binds only moderately to blood proteins (55%) and is cleared through the kidneys, so after an injection under the skin its half-life is about 3 hours, with peak levels after 1 to 3.5 hours. That makes it a short-acting GLP-1 agonist, injected once a day before a meal.

How it works

Lixisenatide binds to the GLP-1 receptor and activates it, which raises cyclic AMP inside the cell. In the pancreas it increases insulin release only when blood glucose is high and lowers glucagon, while the glucagon response to low blood sugar is preserved. On its own it therefore rarely causes hypoglycaemia.

Because it acts for only a few hours, its clearest effect is on the rise in glucose after a meal. It slows the emptying of the stomach, so that glucose from food enters the blood more slowly. In a four-week study in people on metformin, lixisenatide reduced the glucose rise after a test meal about three times as much as liraglutide (−12.61 against −4.04 h·mmol/L).

Is lixisenatide approved?

Yes, but since the end of 2025 it has been available in the EU and the US only in a fixed combination with insulin glargine. The stand-alone medicine was withdrawn in the EU at Sanofi's request, and in the US it is no longer marketed.

In the Netherlands Suliqua is now the only medicine that contains lixisenatide. It is prescription-only, and basic health insurance reimburses it only under the conditions in annex 2 of the Regeling zorgverzekering. In its advice on GLP-1 agonists for people at very high cardiovascular risk, the Farmacotherapeutisch Kompas notes that any added value of lixisenatide has not yet been sufficiently shown.

• EU, Lyxumia: authorised on 1 February 2013 for adults with type 2 diabetes, together with oral glucose-lowering drugs and/or basal insulin. On 18 December 2025 the European Commission withdrew the authorisation at the request of Sanofi, which had decided to stop marketing it permanently for commercial reasons.
• EU, Suliqua: insulin glargine and lixisenatide in one pen, authorised on 11 January 2017 and still authorised. Since 2020 the indication is adults with insufficiently controlled type 2 diabetes, on top of metformin with or without an SGLT2 inhibitor. In August 2026 the product information added a way to switch over from premixed insulin, based on the SoliSwitch study.
• US, Adlyxin: approved on 27 July 2016 for adults with type 2 diabetes. It has not been marketed since 2023; the FDA's listing data give 30 September 2023 as the end of marketing, while the licence itself remains active in Drugs@FDA.
• US, Soliqua 100/33: approved on 21 November 2016, at first for adults not controlled on basal insulin or lixisenatide, and in February 2019 also for adults not controlled on oral diabetes drugs. Its label now covers adults with type 2 diabetes, as an adjunct to diet and exercise.

What the research shows

Lixisenatide on its own went through the GetGoal phase 3 programme: according to the EU product information, nine double-blind placebo-controlled trials with 4,508 people, 2,869 of them on lixisenatide, plus open trials against exenatide and mealtime insulin. ELIXA, funded by Sanofi, tested its cardiovascular safety, and the LixiLan trials tested the combination with insulin glargine. The headline results:

• GetGoal, 24 weeks: added to metformin, HbA1c fell by 0.92 percentage points on lixisenatide against 0.42 on placebo in one trial; added to a sulfonylurea with or without metformin, by 0.85 against 0.10. With metformin and/or a sulfonylurea, body weight fell by 1.8 to 3.0 kg, but the placebo groups lost weight too (in that metformin trial −2.6 against −1.6 kg).
• GetGoal-X (Diabetes Care 2013): 634 people on metformin, open-label against exenatide twice daily; after 24 weeks HbA1c fell by 0.79 against 0.96 percentage points, which met the preset margin for non-inferiority. Nausea occurred in 24.5% against 35.1% and symptomatic hypoglycaemia in 2.5% against 7.9%.
• ELIXA (NEJM 2015): 6,068 people with type 2 diabetes and a heart attack or hospital admission for unstable angina in the previous 180 days, followed for a median of 25 months. Cardiovascular death, heart attack, stroke or hospitalisation for unstable angina occurred in 13.4% on lixisenatide against 13.2% on placebo (hazard ratio 1.02; 95% CI 0.89 to 1.17): not worse than placebo, but not better. Hospitalisation for heart failure (hazard ratio 0.96) and death from any cause (0.94) did not differ either.
• LixiLan-O: 1,170 people on metformin with or without another oral drug; after 30 weeks average HbA1c had fallen from 8.1% to 6.5% on Suliqua, against 6.8% on insulin glargine alone and 7.3% on lixisenatide alone.
• LixiLan-L: 736 people on basal insulin; after 30 weeks HbA1c had fallen from 8.1% to 6.9% on Suliqua, against 7.5% on insulin glargine alone. LixiLan-G: in 514 people on a GLP-1 agonist, both groups started at an HbA1c of 7.8%; after 26 weeks it was 6.7% in those switched to Suliqua and 7.4% in those who stayed on their GLP-1 agonist.

Lixisenatide and Parkinson's disease

GLP-1 receptors are also found in the brain, and lixisenatide protected nerve cells in a mouse model of Parkinson's disease. LIXIPARK, a French phase 2 trial led by Toulouse University Hospital and funded by the French Ministry of Health and others, tested whether it slows the disease in people. It enrolled 156 people diagnosed less than three years earlier, on a stable dose of Parkinson's medication and without motor complications, who received lixisenatide or placebo daily for 12 months, double-blind.

After 12 months the motor score (MDS-UPDRS part III, measured on medication; baseline about 15 on a scale to 132) had changed by −0.04 points on lixisenatide and +3.04 points on placebo, a difference of 3.08 points (95% CI 0.86 to 5.30). Two months after stopping, scores measured off medication were 17.7 against 20.6. The other secondary outcomes did not differ much, and 46% of the lixisenatide group had nausea and 13% vomiting.

This is one small, one-year trial with a modest effect on a single scale. The authors called for longer and larger trials; in October 2026 ClinicalTrials.gov listed no follow-up trial of lixisenatide in Parkinson's disease. A phase 3 trial of a related GLP-1 drug, weekly exenatide, has since reported: Exenatide-PD3 (194 people in the UK over 96 weeks, Lancet 2025) found no difference from placebo. Lixisenatide is not authorised for Parkinson's disease anywhere.

Side effects and warnings

Most side effects are gastrointestinal and come early. In the placebo-controlled trials nausea occurred in 26.1% on lixisenatide against 6.2% on placebo and vomiting in 10.5% against 1.8%, mostly mild and in the first three weeks. The US label also lists headache (9% against 6%), diarrhoea (8% against 6%) and dizziness (7% against 4%). In all, 7.4% stopped because of side effects, against 3.2% on placebo.

Low blood sugar is mainly a problem in combination. Symptomatic hypoglycaemia occurred in 1.7% on lixisenatide alone (placebo 1.6%), but in 47.2% against 21.6% when it was added to both basal insulin and a sulfonylurea, which is why the EU label ruled out that combination. With Suliqua, which contains insulin, low blood sugar is the most common side effect.

The product information also warns about acute pancreatitis, dehydration and kidney injury after vomiting or diarrhoea, gallstones and gallbladder inflammation, and inhaling stomach contents during general anaesthesia or deep sedation; it is not recommended in severe gastroparesis or severe kidney impairment. Possible allergic reactions were reported in 0.4% on lixisenatide against less than 0.1% on placebo, and anaphylaxis in 0.2% against none. About 70% of participants formed antibodies against lixisenatide within 24 weeks; on average the effect on HbA1c was the same with or without them. Because it slows stomach emptying, it can delay the absorption of tablets taken after the injection.

In rats and mice lixisenatide caused thyroid C-cell tumours, a GLP-1 effect to which rodents are particularly sensitive. Unlike the labels of liraglutide and semaglutide, the US labels of Adlyxin and Soliqua carry no boxed warning about them. Suliqua is not recommended in pregnancy or in women who could become pregnant and do not use contraception.

Frequently asked questions

Is lixisenatide still available?

Not on its own. The European Commission withdrew Lyxumia on 18 December 2025 at Sanofi's request, for commercial reasons, and Adlyxin has not been marketed in the US since 2023. Lixisenatide is still prescribed as part of Suliqua in the EU, the Netherlands included, and Soliqua 100/33 in the US, both fixed combinations with insulin glargine. In the Netherlands Suliqua is prescription-only and reimbursed under conditions.

What is the difference between Lyxumia, Adlyxin, Suliqua and Soliqua?

Lyxumia (EU) and Adlyxin (US) were the stand-alone lixisenatide pens, and neither is on the market any more. Suliqua (EU) and Soliqua 100/33 (US) combine lixisenatide with the long-acting insulin glargine in one daily injection, so the lixisenatide dose rises and falls with the insulin dose. The EU has two Suliqua pens with different ratios of insulin to lixisenatide, the US a single Soliqua strength.

Does lixisenatide protect the heart like liraglutide or semaglutide?

There is no evidence that it does. In ELIXA, 6,068 people with type 2 diabetes and a recent heart attack or unstable angina had major cardiovascular events about as often on lixisenatide as on placebo (13.4% against 13.2%). Liraglutide in LEADER and semaglutide in SUSTAIN 6 did lower such events, but in different populations, so the trials cannot be compared directly. The Farmacotherapeutisch Kompas notes that any added value of lixisenatide has not yet been sufficiently shown.

Can lixisenatide slow Parkinson's disease?

That has not been shown. In the French phase 2 trial LIXIPARK (NEJM 2024), 156 people with early Parkinson's disease received lixisenatide or placebo for a year; motor symptoms stayed stable on lixisenatide and worsened by about 3 points on placebo, on a scale that runs to 132. Other outcomes hardly differed, nearly half had nausea, and no follow-up trial was registered by October 2026. Lixisenatide is not authorised for Parkinson's disease.

Does lixisenatide cause weight loss?

A little. In the 24-week trials alongside metformin and/or a sulfonylurea, people on lixisenatide lost 1.8 to 3.0 kg on average, but the placebo groups lost weight too, for example 2.6 against 1.6 kg in one metformin trial. Lixisenatide was never authorised for weight management. In Suliqua it mainly offsets insulin: the EMA concluded that the combination reduced problems of intensive insulin treatment such as weight gain and low blood sugar.

Is lixisenatide banned in sport?

Lixisenatide itself is not: GLP-1 agonists are not on the WADA Prohibited List. Suliqua and Soliqua are a different matter, because they also contain insulin glargine, and insulins are prohibited at all times under class S4.4.2 of the 2026 list. An athlete with diabetes needs a therapeutic use exemption to use them. The Dutch translation of the list by the Dopingautoriteit carries the same text.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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