Lixisenatide

A 44-amino-acid exendin-4 derivative and once-daily, short-acting GLP-1 receptor agonist approved by the FDA in 2016 for type 2 diabetes; the standalone pen was withdrawn from the US market in 2023, leaving only the fixed-ratio insulin glargine combination.

Also referenced as: Adlyxin, Lyxumia, Soliqua, Soliqua 100/33, Suliqua, iGlarLixi, insulin glargine/lixisenatide, AVE0010, AVE-0010, ZP10, ZP-10, ZP10A, des-38-proline-exendin-4 hexalysine, lixisenatida

Also appears in: Weight loss

COA Public product evidence No certificate records are bound to a tracked Lixisenatide product page A record counts here only when a vendor publishes a certificate against one of its own tracked Lixisenatide product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

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What is Lixisenatide?

Lixisenatide is a synthetic 44-amino-acid peptide built on the exendin-4 backbone, the Gila monster venom peptide that also underlies exenatide: the proline at position 38 is deleted and a six-lysine tail is added at the amidated C-terminus. Like exendin-4, it keeps the position-2 glycine that protects the molecule from dipeptidyl peptidase-4, but its terminal half-life is only about 3 hours, which makes it a short-acting, once-daily GLP-1 receptor agonist whose effect is concentrated on the meal that follows the injection. It was discovered by Zealand Pharma (ZP10) and developed by Sanofi (AVE0010), approved in the European Union as Lyxumia in 2013 and by the FDA as Adlyxin on July 27, 2016, followed on November 21, 2016 by Soliqua 100/33, a fixed-ratio combination with insulin glargine.

It appears in peptide conversations for three reasons that have little to do with the research-vendor market: it was the first GLP-1 receptor agonist to complete a dedicated cardiovascular outcomes trial, it is the GLP-1 agonist half of the only insulin glargine fixed-ratio pen sold in the United States, and in 2024 it produced the first positive placebo-controlled Phase 2 result for the GLP-1 class in Parkinson’s disease, a 156-patient trial that met its primary motor endpoint. Lixisenatide has essentially no presence as a research-market peptide; it is encountered almost exclusively as a pharmacy pen.

How it works

Lixisenatide is a selective GLP-1 receptor agonist. Its pharmacology differs from the long-acting agonists (liraglutide, dulaglutide, semaglutide) mainly in duration: a short half-life produces strong, sustained gastric slowing and a pronounced effect on the glucose rise after the next meal, with less effect on fasting glucose and smaller changes in heart rate.

• Glucose-dependent insulin secretion and glucagon suppression — at the pancreatic GLP-1 receptor, lixisenatide enhances insulin release only when glucose is elevated and reduces inappropriate glucagon secretion; in preclinical work it protected a rat beta-cell line from lipid- and cytokine-induced apoptosis, preserved insulin content in human islets exposed to lipotoxicity, and lowered basal glucose and HbA1c in animal models of type 2 diabetes (Werner et al., Regulatory Peptides, 2010, 164(2–3):58–64)
• Marked, sustained delay of gastric emptying — in a 28-day randomized, double-blind, placebo-controlled study of 43 patients with type 2 diabetes, lixisenatide 20 mcg once daily lengthened the gastric half-emptying time of a standardized breakfast by a mean of about 212 minutes versus essentially no change with placebo, and the reduction in post-breakfast glucose exposure correlated inversely with gastric emptying (r² = 0.51), supporting gastric slowing as the main driver of its postprandial effect (Lorenz et al., Regulatory Peptides, 2013, 185:1–8)
• A postprandial rather than fasting profile — in a mechanistic 8-week trial of 142 insulin glargine–treated patients, lixisenatide 20 mcg reduced the 4-hour postprandial glucose area under the curve more than liraglutide 1.2 or 1.8 mg and delayed gastric emptying to a greater extent, while fasting glucose was unchanged in every arm; liraglutide raised 24-hour heart rate by 9 bpm versus 3 bpm with lixisenatide and increased lipase, whereas symptomatic hypoglycemia was more frequent with lixisenatide (Meier et al., Diabetes Care, 2015, 38(7):1263–1273)
• Immunogenicity — the molecule is a non-human sequence, and about 70% of patients in pooled trials had anti-lixisenatide antibodies at week 24; glycemic response was attenuated only in the small subset with the highest antibody concentrations (about 2.4%), but antibody-positive patients had more allergic and injection-site reactions (Adlyxin and Soliqua labels)

Research status

Lixisenatide’s human evidence base is large and mature for type 2 diabetes, neutral for cardiovascular outcomes, and early-stage but notable for Parkinson’s disease.

Type 2 diabetes (GetGoal program). Sanofi’s phase 3 program comprised roughly a dozen trials under the GetGoal name. In GetGoal-Mono, 361 drug-naive patients were randomized to lixisenatide (one- or two-step titration to 20 mcg) or placebo for 12 weeks; HbA1c fell by 0.54% to 0.66% more than placebo, about 2 kg of weight was lost in all groups, nausea occurred in 23% of lixisenatide patients versus 4.1% on placebo, and symptomatic hypoglycemia was rare (1.7% vs 1.6%) (Fonseca et al., Diabetes Care, 2012, 35(6):1225–1231). GetGoal-X randomized 634 metformin-treated patients to lixisenatide once daily or exenatide twice daily for 24 weeks; HbA1c changes were −0.79% versus −0.96%, meeting the 0.4% non-inferiority margin, with less symptomatic hypoglycemia (2.5% vs 7.9%) and less nausea (24.5% vs 35.1%) on lixisenatide (Rosenstock et al., Diabetes Care, 2013, 36(10):2945–2951). GetGoal-L showed the add-on benefit in patients already on basal insulin (Riddle et al., Diabetes Care, 2013, 36(9):2489–2496). The fixed-ratio combination was supported by LixiLan-O in patients on oral agents (Rosenstock et al., Diabetes Care, 2016, 39(11):2026–2035) and LixiLan-L in patients already on basal insulin (Aroda et al., Diabetes Care, 2016, 39(11):1972–1980); a safety review of the combination concluded that its hypoglycemia and gastrointestinal profile compared favorably with its components despite better glycemic control (Frias et al., Diabetes Therapy, 2019, 10(1):21–33).

Cardiovascular outcomes (ELIXA). ELIXA (NCT01147250) was the first completed cardiovascular outcomes trial for any GLP-1 receptor agonist. It randomized 6,068 patients with type 2 diabetes and an acute coronary syndrome within the prior 180 days to lixisenatide or placebo and followed them for a median of 25 months. The primary composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina occurred in 13.4% of the lixisenatide group and 13.2% of the placebo group (hazard ratio 1.02, 95% CI 0.89–1.17), establishing non-inferiority but not superiority; hospitalization for heart failure (HR 0.96) and death (HR 0.94) did not differ, and there was no excess of severe hypoglycemia, pancreatitis, or pancreatic neoplasms (Pfeffer et al., New England Journal of Medicine, 2015, 373(23):2247–2257). The neutral result is the reason lixisenatide carries no cardiovascular-benefit claim, in contrast to liraglutide, semaglutide, and dulaglutide, whose later trials showed risk reduction.

Parkinson’s disease (LIXIPARK). Building on the exenatide signal in Parkinson’s, a placebo-controlled trial of 62 randomized patients in which off-medication motor scores separated by 3.5 points at 60 weeks (Athauda et al., Lancet, 2017, 390(10103):1664–1675), the French NS-Park/F-CRIN network ran a phase 2, double-blind, placebo-controlled trial (NCT03439943; sponsor Toulouse University Hospital; funded by the French Ministry of Health and Cure Parkinson’s, with Sanofi listed as an industry collaborator). A total of 156 patients diagnosed within the previous 3 years received daily subcutaneous lixisenatide or placebo for 12 months followed by a 2-month washout. MDS-UPDRS part III motor scores (baseline about 15) changed by −0.04 points with lixisenatide versus +3.04 with placebo at 12 months (difference 3.08 points, 95% CI 0.86–5.30, P = 0.007), and the separation persisted off medication at 14 months; secondary endpoints did not differ substantially. Nausea occurred in 46% of lixisenatide recipients and vomiting in 13%, and the authors called for longer and larger trials before any clinical use (Meissner et al., New England Journal of Medicine, 2024, 390(13):1176–1185). The class signal has since weakened: the 194-patient phase 3 exenatide trial that followed the 2017 study found no benefit on off-medication motor scores at 96 weeks (Vijiaratnam et al., Lancet, 2025, 405(10479):627–636); that report has carried an Expression of Concern since June 22, 2026, after regulatory inspection findings at one of its six sites, and as of October 2026 it has not been corrected or retracted (Lancet, 2026, 407(10548):2588). As of October 2026, no phase 3 or follow-up lixisenatide trial in Parkinson’s disease is registered on ClinicalTrials.gov, and the withdrawal of the standalone pen leaves no commercial formulation suited to non-diabetic patients. Preclinical Alzheimer’s work exists in rodents (Cai et al., Neuroscience, 2014, 277:6–13; Cai et al., Biochemical and Biophysical Research Communications, 2018, 495(1):1034–1040) without human trials.

Regulatory record. Adlyxin (NDA, later BLA 208471) was approved July 27, 2016 and Soliqua 100/33 (BLA 208673) on November 21, 2016; both were deemed biologics on March 23, 2020. Sanofi withdrew Adlyxin from US distribution in January 2023 as a commercial decision rather than for safety or efficacy, while continuing Soliqua; FDA’s discontinuation list records lixisenatide injection as discontinued, and the product no longer appears in the NDC directory. The application itself has not been withdrawn: Drugs@FDA still lists both Adlyxin strengths with Prescription marketing status and records labeling supplements approved as recently as March 12, 2026, and a September 2023 Adlyxin label remains on DailyMed. The Soliqua label was most recently revised in March 2026 and carries the GLP-1 class warning on pulmonary aspiration during general anesthesia or deep sedation. No generic lixisenatide, new indication, or new formulation has been approved in the United States in 2025 or 2026; currently registered studies are phase 4 or observational uses of the glargine combination, mostly in China.

Common dosage forms

• Fixed-ratio prefilled pen (the only US product currently distributed) — Soliqua 100/33 SoloStar, a 3 mL single-patient-use pen containing 100 units/mL insulin glargine and 33 mcg/mL lixisenatide; the dial delivers 15 to 60 units per injection, corresponding to 5 to 20 mcg of lixisenatide. Marketed in the EU as Suliqua since January 2017 in two pens: the same 100/33 pen (30–60 units) and a 100 units/mL + 50 mcg/mL pen (10–40 units) that carries more lixisenatide per unit of insulin for patients on lower insulin doses.
• Standalone prefilled pens (withdrawn in the US, still approved in principle) — Adlyxin was supplied as a green 50 mcg/mL starter pen delivering 14 doses of 10 mcg and a burgundy 100 mcg/mL maintenance pen delivering 14 doses of 20 mcg. The same presentation remains available as Lyxumia in some markets outside the United States.
• No vial, oral, or depot form — lixisenatide has never been marketed as a vial, lyophilized powder, tablet, or extended-release injection for human use.
• Research supply — effectively absent. Lixisenatide acetate appears in analytical-standard catalogs for laboratory assay work, but it is not a staple of the research-peptide market, which has concentrated on semaglutide, tirzepatide, and retatrutide; lyophilized lixisenatide sold under a research label has no supporting data on potency, stability, or reconstitution.

Key considerations

• Approved, but accessible only inside a combination. Lixisenatide’s FDA Approved status rests on two approved biologic applications. The standalone pen left the US market in January 2023 for commercial reasons, so the molecule is obtainable by prescription only as Soliqua 100/33, bound to insulin glargine in a fixed ratio. That packaging makes it unusable for any non-diabetic research question, which is the obstacle facing any Parkinson’s follow-up. Nothing in the record supports use for weight management as such: the approved indication is glycemic control in adults with type 2 diabetes, and the weight effect in trials was modest (about 2 kg).
• The Parkinson’s result is a single phase 2 trial with a small effect and a heavy tolerability cost. A 3-point MDS-UPDRS III difference at 12 months is statistically clear but near the threshold of clinical relevance, secondary endpoints were flat, and nearly half of treated patients had nausea. The larger exenatide phase 3 that followed was negative, no confirmatory lixisenatide trial is registered, and there is no formulation suited to the population. This is a disease-modification hypothesis, not a treatment.
• Cardiovascular neutrality, not benefit. ELIXA showed that lixisenatide neither raised nor lowered major cardiovascular events after an acute coronary syndrome. Lixisenatide should not be grouped with the GLP-1 agonists that carry labeled cardiovascular risk-reduction indications.
• Class and molecule-specific safety signals. Labeled warnings include anaphylaxis and serious hypersensitivity (more common in antibody-positive patients), acute pancreatitis, acute kidney injury from volume depletion, acute gallbladder disease, hypoglycemia when combined with insulin or sulfonylureas, and pulmonary aspiration during general anesthesia or deep sedation. Because gastric emptying is slowed strongly, the label asks that oral antibiotics and acetaminophen be taken at least 1 hour before the injection and oral contraceptives at least 1 hour before or 11 hours after. Unlike the long-acting agonists, neither the Adlyxin nor the Soliqua label carries a thyroid C-cell tumor boxed warning; the drug has not been studied in patients with a history of pancreatitis and is not recommended in gastroparesis.
• Naming and class confusions. Lixisenatide (AVE0010, ZP10) is an exendin-4 derivative and is often confused with exenatide, which is the unmodified 39-residue exendin-4; the two differ in the deleted proline and six-lysine tail and in dosing frequency, and lixisenatide is not a generic of exenatide. Soliqua 100/33 and Suliqua are the same combination; the “33” is the lixisenatide concentration in mcg/mL, not a dose. Adlyxin and Lyxumia are the same monocomponent product under different regional names.