Section 01
What it's used for
Type 2 Diabetes (Approved)
Lixisenatide is an approved drug that mainly lowers blood-sugar spikes after meals. In trials (GetGoal-Mono, GetGoal-M, and a pooled 76-week analysis), it lowered HbA1c by 0.4-0.66% versus placebo. ELIXA found it neutral for heart risk.
▸Clinical wording
Lixisenatide, an approved GLP-1 receptor agonist, is characterized as a postprandial glucose specialist. In placebo-controlled human trials (GetGoal-Mono, GetGoal-M, and a pooled 76-week GetGoal-programme meta-analysis), it reduced HbA1c by roughly 0.4% to 0.66% versus placebo. The ELIXA cardiovascular outcomes trial confirmed cardiovascular safety, with a neutral effect on major adverse cardiovascular events (MACE).
Combined with Basal Insulin
A fixed-ratio combination of lixisenatide with long-acting insulin glargine, marketed as Soliqua, covers fasting blood sugar and after-meal spikes together, delivered in a single daily injection for people with type 2 diabetes.
▸Clinical wording
Fixed-ratio combination with insulin glargine (Soliqua) provides complementary fasting + postprandial coverage.
Section 02
Mechanism of Action
A rebuilt copy of a gut hormone
- It is a redesigned version of a natural gut hormone with several deliberate chemical changes.
- Those changes shield it from the blood enzyme that normally chops such hormones apart (DPP-4).
- It grips the gut-hormone receptor up to four times as tightly as the natural hormone.
- It clears from blood within about three hours, mostly through the kidneys, so it counts as short-acting.
▸Clinical wording
GLP-1 receptor engagement by an exendin-4 backbone
Lixisenatide is a 44-amino-acid peptide built on exendin-4, with a proline deleted and six lysine residues added at the C-terminus plus amidation at position 44; those changes make it resistant to degradation by DPP-4 (Leon 2017; Andreasen 2021). Its affinity for the GLP-1 receptor is reported as up to four times that of human GLP-1, with a mean terminal half-life near three hours, roughly 55% plasma protein binding and elimination primarily by glomerular filtration (Leon 2017). The target itself, GLP-1R, is a class B seven-transmembrane G protein-coupled receptor within the glucagon receptor superfamily (Liu 2024). The short half-life places it in the short-acting agonist class.
How the signal reaches insulin granules
- Inside the insulin cell the receptor raises a messenger molecule (cAMP) that switches on two relay enzymes.
- Those relays shut a potassium gate in the cell wall, which changes the cell's electrical charge.
- The charge change opens calcium gates, and both relays pull further calcium from internal stores.
- Rising calcium primes and pushes out the packets of stored insulin.
▸Clinical wording
cAMP, PKA and Epac amplification of insulin secretion
In beta cells the receptor couples to the trimeric G protein complex and releases the activated Gas subunit, which activates membrane-bound adenylyl cyclase to produce cAMP; cAMP then acts through two effectors, PKA and Epac (cAMP-GEF). PKA phosphorylates the SUR1 subunit, disrupting ADP binding and tipping KATP channel regulation toward closure, while an Epac-selective cAMP analogue lowers the ATP concentration needed for half-maximal channel inhibition. Depolarisation opens voltage-dependent Ca2+ channels; Epac sensitises ryanodine receptors and PKA sensitises IP3 receptors, adding calcium-induced calcium release, and Epac action on granular SUR1 aids granule priming (Meloni 2012).
Why the effect depends on blood sugar
- Each step of the chain only works when sugar is high, and stalls when it is low.
- Fasting volunteers given the natural hormone by infusion did not drop into low blood sugar.
- For this peptide the boost to insulin release was strictly tied to glucose levels.
- In rat cells and human islet tissue it also limited cell death and insulin loss.
▸Clinical wording
Why the insulinotropic effect tracks ambient glucose
Meloni and colleagues locate the glucose gate at several points. PKA-driven KATP closure depends on the low ADP seen under high glucose, and at low glucose the effect is negligible; calcium-induced calcium release does not occur when nifedipine blocks voltage-dependent channels; and ADP abolishes granule acidification even in the presence of ATP. Fasting humans infused with GLP-1 exhibited no hypoglycaemia. For lixisenatide specifically, improvement of glucose-stimulated insulin secretion occurred in a strictly glucose-dependent manner, alongside protection of rat Ins-1 beta cells from apoptosis and prevention of lipotoxicity-induced insulin depletion in human islets (Werner 2010).
Slower stomach emptying after meals
- In rats the slowing of the stomach runs through a nerve line from gut to brain.
- Only short-acting versions keep the slowing going; constant stimulation makes the response fade.
- In a 142-patient trial it slowed emptying more than liraglutide and lowered after-meal glucose.
- Fasting blood sugar did not change in any group of that trial.
▸Clinical wording
Gastric emptying restraint and postprandial glucose
Experimental data from rats indicate that the inhibitory effect of GLP-1 on gastric motor function is mediated by the afferent vagal nerve through GLP-1R located on vagal afferent fibres, and that only short-acting agonists sustain a marked slowing, since chronic near-continuous receptor activation produces tachyphylaxis (Liu 2024; Andreasen 2021). In a 142-patient trial on optimised insulin glargine, 8 weeks of lixisenatide 20 ug delayed gastric emptying more than liraglutide 1.2 or 1.8 mg (P<0.001) and reduced the 4-hour postprandial glucose AUC by 6.0 and 4.6 h.mmol/L versus those arms, while fasting plasma glucose was unchanged in every arm (Meier 2015).
The sugar-raising hormone and food intake
- The sugar-raising hormone glucagon is damped at normal or high blood sugar but not when sugar is low.
- That damping looks indirect, passing through another pancreatic messenger rather than acting on the cells directly.
- After breakfast it cut glucagon and insulin in type 2 diabetes, but not after a late lunch.
- In 30 volunteers it lowered food intake, and that drop did not track the stomach slowing.
▸Clinical wording
Glucagon suppression and central control of energy intake
GLP-1 suppresses glucagon under normo- and hyperglycaemia but not during hypoglycaemia, and somatostatin receptor 2 antagonist experiments indicate the alpha-cell action is indirect, partly somatostatin-mediated (Liu 2024). After breakfast, lixisenatide significantly reduced glucagon and insulin secretion in type 2 diabetes, with the effect lost after a late lunch (Meier 2020). GLP-1R is densely expressed in the rat area postrema, which lacks a blood-brain barrier. In 15 healthy volunteers and 15 patients with type 2 diabetes, lixisenatide markedly slowed emptying and cut energy intake, yet that fall was unrelated to the change in gastric emptying or intragastric distribution (Jalleh 2020).
Section 03
Biological Pathways
- GLP-1R/cAMP/PKA/Epac signalingLixisenatide, with roughly fourfold GLP-1's receptor affinity, raises beta cell cAMP via Gas-adenylyl cyclase; PKA phosphorylates SUR1 to close KATP channels while Epac aids granule priming.
- Glucose-dependent insulinotropic gatingThe insulin response tracks glucose because PKA-driven KATP closure needs the low ADP seen only at high glucose; lixisenatide's secretion also protected beta cells from apoptosis and lipotoxicity.
- Vagal afferent gastric emptying delayGLP-1R on vagal afferent fibers mediates slowed gastric motility; being short-acting, lixisenatide avoids tachyphylaxis and delayed emptying more than liraglutide in one trial, cutting postprandial glucose.
- Glucagon suppression and central accessLixisenatide suppresses glucagon under normo- and hyperglycemia via a partly somatostatin-mediated indirect action, but not hypoglycemia; GLP-1R is dense in the rat area postrema, which lacks a blood-brain barrier.
- Modest appetite effect vs longer agonistsIn healthy volunteers and type 2 diabetes patients, lixisenatide slowed gastric emptying and cut energy intake, though central appetite suppression is modest versus longer-acting GLP-1 receptor agonists.
Section 04
Dosage Information
Modified exendin-4 with C-terminal hexa-lysine extension| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — diabetes label | FDA label, type 2 diabetes (Adlyxin / Lyxumia), adults | 10 µg daily for 14 days, then 20 µg from day 15 — about 0.22–0.29 µg/kg a day at 70–90 kg; injected an hour before the first meal | One maintenance dose and no step above it if 20 µg falls short; the label calls 10 µg too low to control glucose. Withdrawn in the US in January 2023. |
| Subcutaneous — fixed mix with insulin | FDA label, fixed mix with insulin glargine (Soliqua) | 0.33 µg per insulin unit — 15 units give 5 µg, 60 units give 20 µg, raised 2–4 units a week against fasting blood sugar to that ceiling | The peptide dose is not chosen here: it follows the insulin need, and the 60-unit ceiling caps both. More insulin means sitting at the lixisenatide maximum. |
| Subcutaneous — cardiovascular trial | Outcome trial after acute coronary syndrome | 20 µg once daily in 6,068 adults with type 2 diabetes, median 25 months; cardiovascular events 13.4% vs 13.2% on placebo | The label dose at a hard endpoint, and it did nothing: no worse than placebo, no better. Liraglutide and dulaglutide cut events in theirs; this one did not. |
| Subcutaneous — Parkinson's trial | Phase 2, early Parkinson's disease | 20 µg once daily for 12 months in 156 people diagnosed within three years; motor score 14.9 vs 18.8 on placebo | About four points on a 132-point scale, in 156 people over one year. Around half had gut side effects and some dropped back to 10 µg. Phase 2 only. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
Before first use, lixisenatide is kept refrigerated at 2-8°C. It is protected from light throughout storage, both before and after opening.
After opening
Once first used, it is kept below 30°C, away from light, and used within 14 days. After that time, any remaining solution is no longer used.
Section 07
Side Effects & Precautions
Nausea (25%), vomiting (10%), diarrhea (8%). GI effects more pronounced initially but resolve over weeks. Lower systemic GI effects compared to long-acting agents. Injection site reactions. Hypoglycemia risk when combined with sulfonylureas or insulin.
Section 08
Regulatory Status
FDA / United States
Approved 2016, discontinued 2023
Adlyxin was approved in 2016; Sanofi discontinued US sales for commercial reasons, and the standalone product left the market on 1 January 2023.
EMA / Europe
Approved 2013, withdrawn 2025
Lyxumia held EU marketing authorisation from 2013, until Sanofi asked the European Commission to withdraw it — effective 18 December 2025 — again for commercial reasons.
Combination survives
Still sold as Soliqua / Suliqua
The fixed-dose combination of lixisenatide with insulin glargine remains on the market in both the US (Soliqua) and the EU (Suliqua), even though the standalone lixisenatide products are gone.
WADA
Not prohibited
GLP-1 receptor agonists — lixisenatide included — do not appear in the S2 or S4 sections of the 2026 Prohibited List; USADA states plainly that GLP-1s are not prohibited in sport.
Regulatory status differs by country and changes over time. A drug's withdrawal from sale is usually a commercial decision, not a safety recall — check current availability and the current Prohibited List before relying on this entry.
Section 09
Research Studies
- [1]Lixisenatide (Adlyxin): A Once-Daily Incretin Mimetic Injection for Type-2 DiabetesLeon N, LaCoursiere R, Yarosh D, Patel RS. · P&T (Pharmacy and Therapeutics) · 2017
- [2]How glucagon-like peptide 1 receptor agonists workAndreasen CR, Andersen A, Knop FK, Vilsboll T. · Endocrine Connections · 2021
- [3]Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonistsLiu QK. · Frontiers in Endocrinology · 2024
- [4]GLP-1 receptor activated insulin secretion from pancreatic beta-cells: mechanism and glucose dependenceMeloni AR, DeYoung MB, Lowe C, Parkes DG. · Diabetes, Obesity and Metabolism · 2013
- [5]Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetesWerner U, Haschke G, Herling AW, Kramer W. · Regulatory Peptides · 2010
- [6]Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without MetforminMeier JJ, Rosenstock J, Hincelin-Mery A, et al. · Diabetes Care · 2015
- [7]Effects of sequential treatment with lixisenatide, insulin glargine, or their combination on meal-related glycaemic excursions, insulin and glucagon secretion, and gastric emptying in patients with type 2 diabetesMeier JJ, Menge BA, Schenker N, et al. · Diabetes, Obesity and Metabolism · 2020
- [8]Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric DistributionJalleh R, Pham H, Marathe CS, et al. · Nutrients · 2020
Section 10
Frequently Asked Questions
Lixisenatide is a short-acting GLP-1 receptor agonist built on the exendin-4 backbone, with a half-life of about three hours versus the multi-day half-lives of drugs like semaglutide or liraglutide. That short action concentrates its effect on slowing gastric emptying after meals, making it a postprandial-glucose specialist rather than an all-day glucose suppressor. It reached the US market as Adlyxin and the EU market as Lyxumia, both for type 2 diabetes.
Adlyxin was withdrawn from the US market in January 2023; the sourced regulatory material notes the withdrawal date but not the manufacturer's stated reason. It remains authorized in the EU as Lyxumia and in the fixed insulin combination Soliqua, so the withdrawal reads as a US commercial decision rather than a global safety action recorded in these sources.
The trials in the sourced material (the GetGoal programme, ELIXA) report HbA1c reduction and cardiovascular safety, not a weight-loss figure. Lixisenatide slows gastric emptying, and one cited study looked specifically at energy intake, but result figures for that study aren't included in this record, so no quantified weight effect can be stated here.
In the ELIXA outcomes trial, 20 µg of lixisenatide daily in over 6,000 people with type 2 diabetes and recent acute coronary syndrome produced no difference from placebo in cardiovascular events (13.4% vs 13.2%) over a median 25 months — a neutral result. By contrast, the outcome trials for liraglutide and dulaglutide showed a reduction in cardiovascular events; lixisenatide's trial only establishes safety, not benefit.
Yes — it is sold as a fixed-ratio combination with insulin glargine (Soliqua). The lixisenatide dose isn't set independently there: 15 units of the mix deliver 5 µg, 60 units deliver 20 µg, and the mix is titrated against fasting blood sugar up to a 60-unit ceiling that caps both drugs together, so higher insulin needs sit at the lixisenatide maximum regardless of dose intent.
Yes, in a phase 2 trial: 20 µg once daily for 12 months in 156 people diagnosed with Parkinson's within the previous three years produced a motor-score difference of about 4 points on a 132-point scale versus placebo (14.9 vs 18.8). About half of participants had gastrointestinal side effects and some were stepped back to 10 µg — one mid-sized phase 2 result, not confirmation.
Gastrointestinal effects dominate: nausea in about 25%, vomiting in about 10%, and diarrhea in about 8%, generally more pronounced when starting and easing over weeks. Injection-site reactions occur, and hypoglycemia risk rises specifically when lixisenatide is combined with sulfonylureas or insulin — its own glucose-dependent mechanism makes hypoglycemia uncommon on its own.